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10.1101/000638

Effects of metsulfuron-methyl on aquatic plant (Lemna gibba L.) and recovery from after prolonged exposure under rice cropping conditions

Raja Rajeswari;Atmakuru Ramesh;

Atmakuru Ramesh

International Institute of bio-technology and toxicology

2013-11-22

Contradictory Results

cc_no

Plant Biology

https://www.biorxiv.org/content/early/2013/11/22/000638.source.xml

The effects and potential recovery of aquatic plant Lemna gibba exposed to a sulfonyl urea herbicide metsulfuron-methyl (MSM) for 120 days under rice cropping condition was investigated. The frond number was decreased by day 15 at the concentration 11 {micro}g/L and 100% inhibition on growth rate of Lemna was observed. Continuous decrease of frond number by day 50 at below the detectable level of residues exhibited symptoms (chlorosis) of MSM toxicity. Toxicity was assessed on the basis of toxicity index (TI) value, growth rate, yield and pigment contents (chlorophyll, carotene, total carotenoid and xanthophyll) of treated samples compared with untreated control. The observed value of 0.698 {micro}g/g chlorophyll a, 0.263 {micro}g/g chlorophyll b, 0.147 {micro}g/g carotene, 1.620 {micro}g/g total carotenoid and 1.473 {micro}g/g xanthophyll contents in treated samples was statistically significantly different from control value of 4.366 {micro}g/g chlorophyll a, 3.132 {micro}g/g chlorophyll b, 0.796 {micro}g/g carotene, 17.755 {micro}g/g total carotenoid and 16.937 {micro}g/g xanthophyll contents by day 50 samples. After prolonged exposure, growth rate, yield and pigment content for the treated samples recovered to control levels on day 120. The obtained data indicate the application of aquatic plant Lemna gibba as sensitive biomarker of water quality as well as the significance of selected biological parameters in the reliable assessment of toxic potential of MSM under rice cropping condition.

biorxiv

10.1101/001248

A conserved oomycete CRN effector targets and modulates tomato TCP14-2 to enhance virulence

Remco Stam;Graham Motion;Petra C. Boevink;Edgar Huitema;

Edgar Huitema

University of Dundee

2013-12-11

New Results

cc_by_nc_nd

Plant Biology

https://www.biorxiv.org/content/early/2013/12/11/001248.source.xml

Phytophthora spp. secrete vast arrays of effector molecules upon infection. A main class of intracellular effectors are the CRNs. They are translocated into the host cell and specifically localise to the nucleus where they are thought to perturb many different cellular processes. Although CRN proteins have been implicated as effectors, direct evidence of CRN mediated perturbation of host processes has been lacking. Here we show that a conserved CRN effector from P. capsici directly binds to tomato transcription factor SlTCP14-2. Previous studies in Arabidopsis thaliana have revealed that transcription factor TCP14 may be key immune signalling protein, targeted by effectors from divergent species. We extend on our understanding of TCP targeting by pathogen effectors by showing that the P. capsici effector CRN12_997 binds to SlTCP14-2 in plants. SlTCP14-2 over-expression enhances immunity to P. capsici, a phenotypic outcome that can be abolished by co-expression of CRN12_997.\n\nWe show that in the presence of CRN12_997, SlTCP14-2 association with nuclear chromatin is diminished, resulting in altered SlTCP14 subnuclear localisation. These results suggest that CRN12_997 prevents SlTCP14 from positively regulating defence against P. capsici. Our work demonstrates a direct interaction between an oomycete CRN and a host target required for suppression of immunity. Collectively, our results hint at a virulence strategy that is conserved within the oomycetes and may allow engineering of resistance to a wide range of crop pathogens.

biorxiv

10.1101/001438

DCL1, a Protein that Produces Plant MicroRNA, Coordinates Meristem Activity

Stephen E. Schauer;Teresa A. Golden;Delwin S. Merchant;Biranchi N. Patra;Jean D. Lang;Sumita Ray;Bulbul Chakravarti;Deb N. Chakravarti;Animesh Ray;

Animesh Ray

Keck Graduate Institute

2013-12-16

New Results

cc_by_nd

Plant Biology

https://www.biorxiv.org/content/early/2013/12/16/001438.source.xml

Abstract Abstract Introduction Results Discussion Materials and Methods Authors' contributions Funding References The ubiquity and importance of short duplex RNAs, termed microRNA (miRNA), for normal development in higher eukaryotes are becoming increasingly clear. We had previously shown that reduction-of-function mutations in Arabidopsis thaliana DCL1 (DICER-LIKE1) gene, affecting the nucleus-localized protein that produces 19-25 nucleotides long miRNA species from longer double stranded RNA precursors, cause a delay in flowering by prolonging the period of juvenile organ development. Here we show that DCL1 transcription is increased at the critical phase of juvenile to reproductive developmental transition, and that DCL1 protein is localized in meri ...

biorxiv

10.1101/001438

DCL1, a Protein that Produces Plant MicroRNA, Coordinates Meristem Activity

Stephen E. Schauer;Teresa A. Golden;Delwin S. Merchant;Biranchi N. Patra;Jean D. Lang;Sumita Ray;Bulbul Chakravarti;Deb N. Chakravarti;Animesh Ray;

Animesh Ray

Keck Graduate Institute

2013-12-21

New Results

cc_by_nd

Plant Biology

https://www.biorxiv.org/content/early/2013/12/21/001438.source.xml

Abstract Abstract Introduction Results Discussion Materials and Methods Authors' contributions Funding References The ubiquity and importance of short duplex RNAs, termed microRNA (miRNA), for normal development in higher eukaryotes are becoming increasingly clear. We had previously shown that reduction-of-function mutations in Arabidopsis thaliana DCL1 (DICER-LIKE1) gene, affecting the nucleus-localized protein that produces 19-25 nucleotides long miRNA species from longer double stranded RNA precursors, cause a delay in flowering by prolonging the period of juvenile organ development. Here we show that DCL1 transcription is increased at the critical phase of juvenile to reproductive developmental transition, and that DCL1 protein is localized in meri ...

biorxiv

10.1101/000950

An XA21-Associated Kinase (OsSERK2) regulates immunity mediated by the XA21 and XA3 immune receptors

Xuewei Chen;Shimin Zuo;Benjamin Schwessinger;Mawsheng Chern;Patrick Canlas;Deling Ruan;Arsalan Daudi;Xiaogang Zhang;Jing Wang;Christopher Petzold;Joshua Heazlewood;Pamela C Ronald;

Pamela C Ronald

Department of Plant Pathology and the Genome Center, University of California, Davis, California 956

2013-11-26

New Results

cc_by_nc_nd

Plant Biology

https://www.biorxiv.org/content/early/2013/11/26/000950.source.xml

The rice XA21 immune receptor kinase and the structurally related XA3 receptor, confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast-two-hybrid system in a kinase activity dependent manner. OsSERK2 undergoes bidirectional trans-phosphorylation with XA21 in vitro and forms a constitutive complex with XA21 in vivo. These results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function. Taken together, our findings suggest that the mechanism of OsSERK2-meditated regulation of rice XA21, XA3 and FLS2 differs from that of AtSERK3/BAK1-mediated regulation of Arabidopsis FLS2 and EFR.

10.1093/mp/ssu003

biorxiv

10.1101/000950

An XA21-Associated Kinase (OsSERK2) regulates immunity mediated by the XA21 and XA3 immune receptors

Xuewei Chen;Shimin Zuo;Benjamin Schwessinger;Mawsheng Chern;Patrick Canlas;Deling Ruan;Arsalan Daudi;Xiaogang Zhang;Jing Wang;Christopher Petzold;Joshua Heazlewood;Pamela C Ronald;

Pamela C Ronald

Department of Plant Pathology and the Genome Center, University of California, Davis, California 956

2013-12-25

New Results

cc_by_nc_nd

Plant Biology

https://www.biorxiv.org/content/early/2013/12/25/000950.source.xml

The rice XA21 immune receptor kinase and the structurally related XA3 receptor, confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast-two-hybrid system in a kinase activity dependent manner. OsSERK2 undergoes bidirectional trans-phosphorylation with XA21 in vitro and forms a constitutive complex with XA21 in vivo. These results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function. Taken together, our findings suggest that the mechanism of OsSERK2-meditated regulation of rice XA21, XA3 and FLS2 differs from that of AtSERK3/BAK1-mediated regulation of Arabidopsis FLS2 and EFR.

10.1093/mp/ssu003

biorxiv

10.1101/000943

Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans

Frederick B. Shipley;Christopher M. Clark;Mark J. Alkema;Andrew M. Leifer;

Andrew M. Leifer

Princeton University

2013-11-27

New Results

cc_by_nc

Neuroscience

https://www.biorxiv.org/content/early/2013/11/27/000943.source.xml

Editor:\n\nA fundamental goal of systems neuroscience is to probe the dynamics of neural activity that generate behavior. Here we present an instrument to simultaneously manipulate and monitor neural activity and behavior in the freely moving nematode Caenorhabditis elegans. We use the instrument to directly observe the relationship between sensory neuron activation, interneuron dynamics and locomotion in the mechanosensory circuit.\n\nPreviously in this journal, we presented an optogenetic illumination system capable of real-time light delivery with high spatial resolution to stimulate or inhibit specified targets in freely moving C. elegans [1]. This \"Colbert\" system and others like it [2] have been instrumental in defining neural coding of several behaviors in C. elegans including chemotaxis [3], nociception [4] and the escape response [5]. Here we integrate the Colbert s ...

10.3389/fncir.2014.00028

biorxiv

10.1101/000943

Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans

Frederick B. Shipley;Christopher M. Clark;Mark J. Alkema;Andrew M. Leifer;

Andrew M. Leifer

Princeton University

2013-12-01

New Results

cc_by_nc

Neuroscience

https://www.biorxiv.org/content/early/2013/12/01/000943.source.xml

Editor:\n\nA fundamental goal of systems neuroscience is to probe the dynamics of neural activity that generate behavior. Here we present an instrument to simultaneously manipulate and monitor neural activity and behavior in the freely moving nematode Caenorhabditis elegans. We use the instrument to directly observe the relationship between sensory neuron activation, interneuron dynamics and locomotion in the mechanosensory circuit.\n\nPreviously in this journal, we presented an optogenetic illumination system capable of real-time light delivery with high spatial resolution to stimulate or inhibit specified targets in freely moving C. elegans [1]. This \"Colbert\" system and others like it [2] have been instrumental in defining neural coding of several behaviors in C. elegans including chemotaxis [3], nociception [4] and the escape response [5]. Here we integrate the Colbert s ...

10.3389/fncir.2014.00028

biorxiv

10.1101/000943

Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans

Frederick B. Shipley;Christopher M. Clark;Mark J. Alkema;Andrew M. Leifer;

Andrew M. Leifer

Princeton University

2014-04-02

New Results

cc_by_nc

Neuroscience

https://www.biorxiv.org/content/early/2014/04/02/000943.source.xml

Editor:\n\nA fundamental goal of systems neuroscience is to probe the dynamics of neural activity that generate behavior. Here we present an instrument to simultaneously manipulate and monitor neural activity and behavior in the freely moving nematode Caenorhabditis elegans. We use the instrument to directly observe the relationship between sensory neuron activation, interneuron dynamics and locomotion in the mechanosensory circuit.\n\nPreviously in this journal, we presented an optogenetic illumination system capable of real-time light delivery with high spatial resolution to stimulate or inhibit specified targets in freely moving C. elegans [1]. This \"Colbert\" system and others like it [2] have been instrumental in defining neural coding of several behaviors in C. elegans including chemotaxis [3], nociception [4] and the escape response [5]. Here we integrate the Colbert s ...

10.3389/fncir.2014.00028

biorxiv

10.1101/001123

Analysis of the study of the cerebellar pinceau by Korn and Axelrad

Antonin Blot;Boris Barbour;

Boris Barbour

Ecole Normale Supérieure

2013-12-03

Contradictory Results

cc_by

Neuroscience

https://www.biorxiv.org/content/early/2013/12/03/001123.source.xml

The axon initial segment of each cerebellar Purkinje cell is ensheathed by basket cell axons in a structure called the pinceau, which is largely devoid of chemical synapses and gap junctions. These facts and ultrastructural similarities with the axon cap of the teleost Mauthner cell led to the conjecture that the pinceau mediates ephaptic (via the extracellular field) inhibition. Korn and Axelrad published a study in 1980 in which they reported confirmation of this conjecture. We have analysed their results and show that most are likely to be explained by an artefactual signal arising from the massive stimulation of parallel fibres they employed. We reproduce their experiments and confirm that all of their results are consistent with this artefact. Their data therefore provide no evidence regarding the operation of the pinceau.

biorxiv

10.1101/001156

Influence of walking speed on locomotor time production

Fabrice MEGROT;Carole MEGROT;

Fabrice MEGROT

French Red Cross

2013-12-04

Contradictory Results

cc_by_nc

Neuroscience

https://www.biorxiv.org/content/early/2013/12/04/001156.source.xml

The aim of the present study was to determine whether or not walking speed affects temporal perception. It was hypothesized that fast walking would reduce the perceived length of time while slow walking increase production estimates. 16 healthy subjects were included. After a first << calibration >> phase allowing the determination of different walking speeds, the subjects were instructed to demonstrate periods of time or << target times >> of 3s and 7s, by a walking movement. Then, subjects were asked to simulate walking by raising one foot after the other without advancing. Finally, a third condition, Motionless, involved producing the target times while standing without movement. The results of this study suggest that movement does influence the perception of time, causing an overestimation of time. In agreement with the results of Denner et al. (1963) the subjects produced times which were longer than the target times.

biorxiv

10.1101/001198

Genomic architecture of human neuroanatomical diversity

Roberto Toro;Jean-Baptiste Poline;Guillaume Huguet;Eva Loth;Vincent Frouin;Tobias Banaschewski;Gareth J Barker;Arun Bokde;Christian Büchel;Fabiana Carvalho;Patricia Conrod;Mira Fauth-Bühler;Herta Flor;Jürgen Gallinat;Hugh Garavan;Penny Gowloan;Andreas Heinz;Bernd Ittermann;Claire Lawrence;Hervé Lemaître;Karl Mann;Frauke Nees;TomᚠPaus;Zdenka Pausova;Marcella Rietschel;Trevor Robbins;Michael Smolka;Andreas Ströhle;Gunter Schumann;Thomas Bourgeron;

Roberto Toro

Institut Pasteur

2013-12-10

New Results

cc_no

Neuroscience

https://www.biorxiv.org/content/early/2013/12/10/001198.source.xml

Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here we show, based on our analyses of neuroimaging and whole-genome genotyping data from 1,765 subjects, that up to 54% of this heritability is captured by large numbers of single nucleotide polymorphisms of small effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.

10.1038/mp.2014.99

biorxiv

10.1101/001214

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

Adam H Marblestone;Evan R Daugharthy;Reza Kalhor;Ian D Peikon;Justus M Kebschull;Seth L Shipman;Yuriy Mishchenko;Je Hyuk Lee;David A Dalrymple;Bradley M Zamft;Konrad P Kording;Edward S Boyden;Anthony M Zador;George M Church;

Adam H Marblestone

Harvard University

2013-12-10

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/12/10/001214.source.xml

We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

biorxiv

10.1101/001214

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

Adam H Marblestone;Evan R Daugharthy;Reza Kalhor;Ian D Peikon;Justus M Kebschull;Seth L Shipman;Yuriy Mishchenko;Je Hyuk Lee;David A Dalrymple;Bradley M Zamft;Konrad P Kording;Edward S Boyden;Anthony M Zador;George M Church;

Adam H Marblestone

Harvard University

2013-12-13

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/12/13/001214.source.xml

We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

biorxiv

10.1101/001214

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

Adam H Marblestone;Evan R Daugharthy;Reza Kalhor;Ian D Peikon;Justus M Kebschull;Seth L Shipman;Yuriy Mishchenko;Je Hyuk Lee;David A Dalrymple;Bradley M Zamft;Konrad P Kording;Edward S Boyden;Anthony M Zador;George M Church;

Adam H Marblestone

Harvard University

2013-12-16

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/12/16/001214.source.xml

We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

biorxiv

10.1101/001214

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

Adam H Marblestone;Evan R Daugharthy;Reza Kalhor;Ian D Peikon;Justus M Kebschull;Seth L Shipman;Yuriy Mishchenko;Je Hyuk Lee;David A Dalrymple;Bradley M Zamft;Konrad P Kording;Edward S Boyden;Anthony M Zador;George M Church;

Adam H Marblestone

Harvard University

2014-04-21

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2014/04/21/001214.source.xml

We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

biorxiv

10.1101/000968

Functional connectivity networks with and without global signal correction

Satoru Hayasaka;

Satoru Hayasaka

Wake Forest School of Medicine

2013-11-26

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/11/26/000968.source.xml

In functional connectivity analyses in BOLD (blood oxygenation level dependent) fMRI data, there is an ongoing debate on whether to correct global signals in fMRI time series data. Although the discussion has been ongoing in the fMRI community since the early days of fMRI data analyses, this subject has gained renewed attention in recent years due to the surging popularity of functional connectivity analyses, in particular graph theory-based network analyses. However, the impact of correcting (or not correcting) for global signals has not been systematically characterized in the context of network analyses. Thus, in this work, I examined the effect of global signal correction on an fMRI network analysis. In particular, voxel-based resting-state fMRI networks were constructed with and without global signal correction. The resulting functional connectivity networks were compared. Without global signal correction, the distributions of the correlation coefficients were positively biased. I also found that, without global signal correction, nodes along the interhemisphic fissure were highly connected whereas some nodes and subgraphs around white-matter tracts became disconnected from the rest of the network. These results from this study show differences between the networks with or without global signal correction.

10.3389/fnhum.2013.00880

biorxiv

10.1101/000968

Functional connectivity networks with and without global signal correction

Satoru Hayasaka;

Satoru Hayasaka

Wake Forest School of Medicine

2013-12-19

New Results

cc_by_nc_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/12/19/000968.source.xml

In functional connectivity analyses in BOLD (blood oxygenation level dependent) fMRI data, there is an ongoing debate on whether to correct global signals in fMRI time series data. Although the discussion has been ongoing in the fMRI community since the early days of fMRI data analyses, this subject has gained renewed attention in recent years due to the surging popularity of functional connectivity analyses, in particular graph theory-based network analyses. However, the impact of correcting (or not correcting) for global signals has not been systematically characterized in the context of network analyses. Thus, in this work, I examined the effect of global signal correction on an fMRI network analysis. In particular, voxel-based resting-state fMRI networks were constructed with and without global signal correction. The resulting functional connectivity networks were compared. Without global signal correction, the distributions of the correlation coefficients were positively biased. I also found that, without global signal correction, nodes along the interhemisphic fissure were highly connected whereas some nodes and subgraphs around white-matter tracts became disconnected from the rest of the network. These results from this study show differences between the networks with or without global signal correction.

10.3389/fnhum.2013.00880

biorxiv

10.1101/001586

Embodied cognition, embodied regulation, and the Data Rate Theorem

Rodrick Wallace;

Rodrick Wallace

New York State Psychiatric Institute

2013-12-23

New Results

cc_by_nd

Neuroscience

https://www.biorxiv.org/content/early/2013/12/23/001586.source.xml

The Data Rate Theorem carries deep implications for theories of embodied cognition, extensions providing a spectrum of necessary conditions dynamic statistical models useful in empirical studies. A large deviations argument, however, implies that the regulation and stabilization of such systems is itself an interpenetrating phenomenon necessarily convoluted with embodied cognition. For humans, the central regulatory role of culture has long been known. Although a ground-state collapse analogous to generalized anxiety appears ubiquitous to such systems, lack of cultural modulation in real-time automatons or distributed cognition man-machine cockpits makes them subject to a pathology under which all possible targets are enemies.

10.1016/j.bica.2014.02.003

biorxiv

10.1101/001586

Embodied cognition, embodied regulation, and the Data Rate Theorem

Rodrick Wallace;

Rodrick Wallace

New York State Psychiatric Institute

2014-01-13

New Results

cc_by_nd

Neuroscience

https://www.biorxiv.org/content/early/2014/01/13/001586.source.xml

The Data Rate Theorem carries deep implications for theories of embodied cognition, extensions providing a spectrum of necessary conditions dynamic statistical models useful in empirical studies. A large deviations argument, however, implies that the regulation and stabilization of such systems is itself an interpenetrating phenomenon necessarily convoluted with embodied cognition. For humans, the central regulatory role of culture has long been known. Although a ground-state collapse analogous to generalized anxiety appears ubiquitous to such systems, lack of cultural modulation in real-time automatons or distributed cognition man-machine cockpits makes them subject to a pathology under which all possible targets are enemies.

10.1016/j.bica.2014.02.003

biorxiv

10.1101/001636

Hippocampal Motifs

Zahra Aghajan;Lavanya Acharya;Jesse Cushman;Cliff Vuong;Jason Moore;Mayank Mehta;

Mayank Mehta

UCLA

2013-12-31

New Results

cc_no

Neuroscience

https://www.biorxiv.org/content/early/2013/12/31/001636.source.xml

Dorsal Hippocampal neurons provide an allocentric map of space1, characterized by three key properties. First, their firing is spatially selective1-3, termed a rate code. Second, as animals traverse through place fields, neurons sustain elevated firing rates for long periods, however this has received little attention. Third the theta-phase of spikes within this sustained activity varies with animals location, termed phase-precession or a temporal code4-10. The precise relationship between these properties and the mechanisms governing them are not understood, although distal visual cues (DVC) are thought to be sufficient to reliably elicit them2,3. Hence, we measured rat CA1 neurons activity during random foraging in two-dimensional VR--where only DVC provide consistent allocentric location information-- and compared it with their activity in real world (RW). Surprisingly, we found little spatial selectivity in VR. This is in sharp contrast to robust spatial selectivity commonly seen in one-dimensional RW and VR7-11, or two-dimensional RW1-3. Despite this, neurons in VR generated approximately two-second long phase precessing spike sequences, termed \"hippocampal motifs\". Motifs, and \"Motif-fields\", an aggregation of all motifs of a neuron, had qualitatively similar properties including theta-scale temporal coding in RW and VR, but the motifs were far less spatially localized in VR. These results suggest that intrinsic, network mechanisms generate temporally coded hippocampal motifs, which can be dissociated from their spatial selectivity. Further, DVC alone are insufficient to localize motifs spatially to generate a robust rate code.

10.1038/nn.3884

biorxiv

10.1101/000224

Water and the biology of *prions* and plaques

Graham K Steel;Phillippa M Wiggins;n/a n/a;

Graham K Steel

2013-11-12

New Results

cc_by

Molecular Biology

https://www.biorxiv.org/content/early/2013/11/12/000224.source.xml

This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high density and low density microdomains. Hydrophobic molecules, including proteins, accumulate selectively into stable populations, enriched in high density water, at charged sites on biopolymers. In enriched high density water, proteins are probably partially unfolded and may precipitate out when released. All extracellular matrices contain such charged polymers. Prions, which have been shown to accumulate in soils and clays containing silicates and aluminates also probably accumulate in extracellular matrices.\n\nRelease of proteins follows hydrolysis of the charged groups by highly reactive high density water. This is normally a slow process but is greatly accelerated by urea. Plaques may form with age and disease because of accumulation of urea and, perhaps, glucose in the blood. This favours precipitation of proteins emerging from matrices, rather than refolding and solution. Dialysis should, therefore, interfere with plaque formation and impede the development of some age-related diseases.

10.1038/npre.2007.1381.1

biorxiv

10.1101/000679

Differentiation-dependent telomeric long non-coding transcription in a model of skeletal myogenesis

Scott Brouilette;Samir Ounzain;Vinit Sawhney;Kenta Yashiro;Yasunori Shintani;Kunihiko Takahashi;Steven Coppen;Takuya Narita;Kelli Torsney;Martin Carrier;Niall Campbell;Ken Suzuki;

Samir Ounzain

University of Lausanne Medical School

2013-11-18

New Results

cc_by_nc_nd

Molecular Biology

https://www.biorxiv.org/content/early/2013/11/18/000679.source.xml

Telomeres comprise the distal ends of eukaryotic chromosomes, serve to maintain genomic integrity and are extended by the ribonucleoprotein telomerase. Recent evidence indicates that telomeres are transcribed to generate long non-coding RNAs (lncRNAs) and that these transcripts (TERRA) may inhibit telomerase activity. In this study we assessed telomerase activity and telomeric lncRNA expression in a mouse model of skeletal myogenesis. Using the C2C12 cell line we demonstrated decreased telomerase activity during differentiation into terminally-differentiated skeletal myotubes. Despite existing in a post-mitotic state, residual telomerase activity remained in C2C12 myotubes, indicating a role independent of telomere extension. Telomeric transcripts were detected in both myoblasts and myotubes, with reduced expression during differentiation correlating with reduced telomerase expression. Our data indicate that in a mouse model of skeletal myogenesis TERRA expression does not reduce telomerase activity, suggesting that their relationship is more complex than originally perceived; the role of telomeric derived lncRNAs in relation to telomerase activity may be cell-type specific. These findings raise the possibility for novel non-telomerase regulatory function for TERRA-lncRNAs during skeletal myogenesis.

biorxiv

10.1101/000869

Virulence in a Pseudomonas syringae Strain with a Small Repertoire of Predicted Effectors

Kevin L Hockett;Marc T Nishimura;Erick Karlsrud;Kevin Dougherty;David A Baltrus;

David A Baltrus

University of Arizona

2013-11-23

New Results

cc_no

Microbiology

https://www.biorxiv.org/content/early/2013/11/23/000869.source.xml

Both type III effector proteins and non-ribosomal peptide toxins play important roles for Pseudomonas syringae pathogenicity in host plants, but whether and how these virulence pathways interact to promote infection remains unclear. Genomic evidence from one clade of P. syringae suggests a tradeoff between the total number of type III effector proteins and presence of syringomycin, syringopeptin, and syringolin A toxins. Here we report the complete genome sequence from P. syringae CC1557, which contains the lowest number of known type III effectors to date and has also acquired genes similar to sequences encoding syringomycin pathways from other strains. We demonstrate that this strain is pathogenic on Nicotiana benthamiana and that both the type III secretion system and a new type III effector family, hopBJ1, contribute to virulence. We further demonstrate that virulence activity of HopBJ1 is dependent on similar catalytic sites as the E. coli CNF1 toxin. Taken together, our results provide additional support for a negative correlation between type III effector repertoires and the potential to produce syringomycin-like toxins while also highlighting how genomic synteny and bioinformatics can be used to identify and characterize novel virulence proteins.

biorxiv

10.1101/000869

Virulence in a Pseudomonas syringae Strain with a Small Repertoire of Predicted Effectors

Kevin L Hockett;Marc T Nishimura;Erick Karlsrud;Kevin Dougherty;David A Baltrus;

David A Baltrus

University of Arizona

2014-04-21

New Results

cc_no

Microbiology

https://www.biorxiv.org/content/early/2014/04/21/000869.source.xml

Both type III effector proteins and non-ribosomal peptide toxins play important roles for Pseudomonas syringae pathogenicity in host plants, but whether and how these virulence pathways interact to promote infection remains unclear. Genomic evidence from one clade of P. syringae suggests a tradeoff between the total number of type III effector proteins and presence of syringomycin, syringopeptin, and syringolin A toxins. Here we report the complete genome sequence from P. syringae CC1557, which contains the lowest number of known type III effectors to date and has also acquired genes similar to sequences encoding syringomycin pathways from other strains. We demonstrate that this strain is pathogenic on Nicotiana benthamiana and that both the type III secretion system and a new type III effector family, hopBJ1, contribute to virulence. We further demonstrate that virulence activity of HopBJ1 is dependent on similar catalytic sites as the E. coli CNF1 toxin. Taken together, our results provide additional support for a negative correlation between type III effector repertoires and the potential to produce syringomycin-like toxins while also highlighting how genomic synteny and bioinformatics can be used to identify and characterize novel virulence proteins.

biorxiv

10.1101/001040

High Genetic Diversity and Adaptive Potential of Two Simian Hemorrhagic Fever Viruses in a Wild Primate Population

Adam L. Bailey;Michael Lauck;Andrea Weiler;Samuel D. Sibley;Jorge M. Dinis;Zachary Bergman;Chase W. Nelson;Michael Correll;Michael Gleicher;David Hyeroba;Alex Tumukunde;Geoffrey Weny;Colin Chapman;Jens Kuhn;Austin Hughes;Thomas C. Friedrich;Tony L. Goldberg;David H. O'Connor;

David H. O'Connor

University of Wisconsin - Madison

2013-12-03

New Results

cc_no

Microbiology

https://www.biorxiv.org/content/early/2013/12/03/001040.source.xml

Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 106 - 107 RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses.

10.1371/journal.pone.0090714

biorxiv

10.1101/001362

Extensive Phenotypic Changes Associated with Large-scale Horizontal Gene Transfer

Kevin Dougherty;Brian A Smith;Autum F Moore;Shannon Maitland;Chris Fanger;Rachel Murillo;David A Baltrus;

David A Baltrus

University of Arizona

2013-12-12

New Results

cc_by_nc_nd

Microbiology

https://www.biorxiv.org/content/early/2013/12/12/001362.source.xml

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e. changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmid and phage, little is known about how size of the acquired region affects the magnitude or number of such costs. Here we describe an amazing breadth of phenotypic changes which occur after a large-scale horizontal transfer event (~1Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.

10.1371/journal.pone.0102170

biorxiv

10.1101/000513

Lack of evidence for the presence of an interferon in invertebrate

Pei-Hui Wang;

Pei-Hui Wang

The University of Hong Kong

2013-11-16

New Results

cc_no

Immunology

https://www.biorxiv.org/content/early/2013/11/16/000513.source.xml

In vertebrates, the interferon (IFN) response is the primary form of innate antiviral defense. Previously (2005), a partial cDNA which could encode an interferon-like protein (IntlP) is reported in shrimp, later Rosa et al. (2008) argue that this partial cDNA should encode a portion of insect mitochondrial ATP synthase (MAS) B-chain. Recently (2009), it is demonstrated IntlP also possess antibacterial activity beside antiviral activity reported before. Lacking of a consensus opinion to the question of whether this gene encodes IntlP or MAS, we try to provide more evidences to identify this gene exactly. Here we obtain the full length cDNAs of IntlP/ MAS in Litopenaeus vannamei, and perform the tissue distribution and induced expression analysis. Our results confirm that IntlP is coded by a mistaken ORF and the actual protein indeed is a L. vannamei mitochondrial ATP synthase (LvMAS) whose function is unknown in antiviral responses.

biorxiv

10.1101/000604

Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders

Claudiu I Bandea;

Claudiu I Bandea

Centers for Disease Control and Prevention

2013-11-18

Contradictory Results

cc_by_nc

Immunology

https://www.biorxiv.org/content/early/2013/11/18/000604.source.xml

Despite decades of research, thousands of studies and numerous advances, the etiologies of Alzheimers Disease (AD), Parkinsons Disease (PD), Huntingtons Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Lobar Degeneration (FTLD-U), Creutzfeldt-Jakob Disease (CJD), Reactive Systemic Amyloidosis (RSA) and many other neurodegenerative and systemic amyloid diseases have not been defined, nor have the pathogenic mechanisms leading to cellular death and disease. Moreover, the biological functions of APP/amyloid-{beta} (A{beta}), tau, -synuclein, huntingtin, TAR DNA-binding protein 43 (TDP-43), prion protein (PrP), amyloid A (AA) and some of the other primary proteins implicated in amyloid diseases are not known. And, there are no successful preventive or therapeutic approaches. Based on a comprehensive analysis and new interpretation of the existing data in context of an evolutionary framework, it is proposed that: (i) A{beta}, tau, -synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system, (ii) the isomeric conformational changes of these proteins and their assembly into various oligomers, plaques, and tangles are not protein misfolding events as defined for decades, nor are they prion-replication activities, but part of their normal, evolutionarily selected innate immune repertoire, and (iii) the immune reactions and activities associated with the function of these proteins in innate immunity lead to AD, PD, HD, ALS, CJD, RSA and other related diseases, which are innate immunity disorders.

biorxiv

10.1101/000844

Genomics via Optical Mapping (I): 0-1 Laws for Mapping with Single Molecules

Thomas Anantharaman;Bud (Bhubaneswar) Mishra;

Bud (Bhubaneswar) Mishra

Courant Inst., New York University

2013-11-22

New Results

cc_by

Genomics

https://www.biorxiv.org/content/early/2013/11/22/000844.source.xml

The genomic data that can be collected from a single DNA molecule by the best chemical and optical methods (e.g., using technologies from OpGen, BioNanoGenomics, NABSys, PacBio, etc.) are badly corrupted by many poorly understood noise processes. Thus, single molecule technology derives its utility through powerful probabilistic modeling, which can provide precise lower and upper bounds on various experimental parameters to create the correct map or validate sequence assembly. As an example, this analysis shows how as the number of \"imaged\" single molecules (i.e., coverage) is increased in the optical mapping data, the probability of successful computation of the map jumps from 0 to 1 for fairly small number of molecules.

biorxiv

10.1101/000935

The-LHON-Enigma: explaining the behaviour of Leber&amp;#146;s Hereditary Optic Neuropathy by the use of a simple computer model

IAN S Logan;

IAN S Logan

-

2013-11-25

New Results

cc_by

Genomics

https://www.biorxiv.org/content/early/2013/11/25/000935.source.xml

Lebers Hereditary Optic Neuropathy (LHON) appears as an enigmatic condition; affecting only certain families and often causing a severe loss of vision seemingly at random amongst family members. The first breakthrough came in 1988 with the linking of the condition to a mutation in the mitochondrial DNA (mtDNA). Now it is known that about 90% of cases are linked to 3 mutations. In this paper the hypothesis is suggested that a LHON mutation decreases the function of the mitochondrial enzyme, Complex I, by 50% and this alone critically endangers the survival of cells - especially the fragile cells of the optic nerves. A computer model has been written to illustrate how the hypothesis can produce a natural history for the condition of LHON that has features similar to those observed in practice; thereby successfully explaining the behaviour of this enigmatic condition.

biorxiv

10.1101/000042

Routes for breaching and protecting genetic privacy

Yaniv Erlich;Arvind Narayanan;

Yaniv Erlich

Whitehead Institute

2013-11-07

New Results

cc_by

Genomics

https://www.biorxiv.org/content/early/2013/11/07/000042.source.xml

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.\n\nAbout the AuthorsYaniv Erlich is a Fellow at the Whitehead Institute for Biomedical Research. Erlich received his Ph.D. from Cold Spring Harbor Laboratory in 2010 and B.Sc. from Tel-Aviv University in 2006. Prior to that, Erlich worked in computer security and was responsible for conducting penetration tests on financial institutes and commercial companies. Dr. Erlichs research involves developing new algorithms for computational human genetics.\n\nArvind Narayanan is an Assistant Professor in the Department of Computer Science and the Center for Information Technology and Policy at Princeton. He studies information privacy and security. His research has shown that data anonymization is broken in fundamental ways, for which he jointly received the 2008 Privacy Enhancing Technologies Award. His current research interests include building a platform for privacy-preserving data sharing.\n\nSummaryO_LIBroad data dissemination is essential for advancements in genetics, but also brings to light concerns regarding privacy.\nC_LIO_LIPrivacy breaching techniques work by cross-referencing two or more pieces of information to gain new, potentially undesirable knowledge on individuals or their families.\nC_LIO_LIBroadly speaking, the main routes to breach privacy are identity tracing, attribute disclosure, and completion of sensitive DNA information.\nC_LIO_LIIdentity tracing exploits quasi-identifiers in the DNA data or metadata to uncover the identity of an unknown genetic dataset.\nC_LIO_LIAttribute disclosure techniques work on known DNA datasets. They use the DNA information to link the identity of a person with a sensitive phenotype.\nC_LIO_LICompletion techniques also work on known DNA data. They try to uncover sensitive genomic areas that were masked to protect the participant.\nC_LIO_LIIn the last few years, we have witnessed a rapid growth in the range of techniques and tools to conduct these privacy-breaching attacks. Currently, most of the techniques are beyond the reach of the general public, but can be executed by trained persons with varying degrees of effort.\nC_LIO_LIThere is considerable debate regarding risk management. One camp supports a pragmatic, ad-hoc approach of privacy by obscurity and the other supports a systematic, mathematically-backed approach of privacy by design.\nC_LIO_LIPrivacy by design algorithms include access control, differential privacy, and cryptographic techniques. So far, data custodians of genetic databases mainly adopted access control as a mitigation strategy.\nC_LIO_LINew developments in cryptographic techniques may usher in an additional arsenal of security by design techniques.\nC_LI

10.1038/nrg3723

biorxiv

10.1101/000042

Routes for breaching and protecting genetic privacy

Yaniv Erlich;Arvind Narayanan;

Yaniv Erlich

Whitehead Institute

2013-11-11

New Results

cc_by

Genomics

https://www.biorxiv.org/content/early/2013/11/11/000042.source.xml

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.\n\nAbout the AuthorsYaniv Erlich is a Fellow at the Whitehead Institute for Biomedical Research. Erlich received his Ph.D. from Cold Spring Harbor Laboratory in 2010 and B.Sc. from Tel-Aviv University in 2006. Prior to that, Erlich worked in computer security and was responsible for conducting penetration tests on financial institutes and commercial companies. Dr. Erlichs research involves developing new algorithms for computational human genetics.\n\nArvind Narayanan is an Assistant Professor in the Department of Computer Science and the Center for Information Technology and Policy at Princeton. He studies information privacy and security. His research has shown that data anonymization is broken in fundamental ways, for which he jointly received the 2008 Privacy Enhancing Technologies Award. His current research interests include building a platform for privacy-preserving data sharing.\n\nSummaryO_LIBroad data dissemination is essential for advancements in genetics, but also brings to light concerns regarding privacy.\nC_LIO_LIPrivacy breaching techniques work by cross-referencing two or more pieces of information to gain new, potentially undesirable knowledge on individuals or their families.\nC_LIO_LIBroadly speaking, the main routes to breach privacy are identity tracing, attribute disclosure, and completion of sensitive DNA information.\nC_LIO_LIIdentity tracing exploits quasi-identifiers in the DNA data or metadata to uncover the identity of an unknown genetic dataset.\nC_LIO_LIAttribute disclosure techniques work on known DNA datasets. They use the DNA information to link the identity of a person with a sensitive phenotype.\nC_LIO_LICompletion techniques also work on known DNA data. They try to uncover sensitive genomic areas that were masked to protect the participant.\nC_LIO_LIIn the last few years, we have witnessed a rapid growth in the range of techniques and tools to conduct these privacy-breaching attacks. Currently, most of the techniques are beyond the reach of the general public, but can be executed by trained persons with varying degrees of effort.\nC_LIO_LIThere is considerable debate regarding risk management. One camp supports a pragmatic, ad-hoc approach of privacy by obscurity and the other supports a systematic, mathematically-backed approach of privacy by design.\nC_LIO_LIPrivacy by design algorithms include access control, differential privacy, and cryptographic techniques. So far, data custodians of genetic databases mainly adopted access control as a mitigation strategy.\nC_LIO_LINew developments in cryptographic techniques may usher in an additional arsenal of security by design techniques.\nC_LI

10.1038/nrg3723

biorxiv

10.1101/000042

Routes for breaching and protecting genetic privacy

Yaniv Erlich;Arvind Narayanan;

Yaniv Erlich

Whitehead Institute

2013-12-01

New Results

cc_by

Genomics

https://www.biorxiv.org/content/early/2013/12/01/000042.source.xml

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.\n\nAbout the AuthorsYaniv Erlich is a Fellow at the Whitehead Institute for Biomedical Research. Erlich received his Ph.D. from Cold Spring Harbor Laboratory in 2010 and B.Sc. from Tel-Aviv University in 2006. Prior to that, Erlich worked in computer security and was responsible for conducting penetration tests on financial institutes and commercial companies. Dr. Erlichs research involves developing new algorithms for computational human genetics.\n\nArvind Narayanan is an Assistant Professor in the Department of Computer Science and the Center for Information Technology and Policy at Princeton. He studies information privacy and security. His research has shown that data anonymization is broken in fundamental ways, for which he jointly received the 2008 Privacy Enhancing Technologies Award. His current research interests include building a platform for privacy-preserving data sharing.\n\nSummaryO_LIBroad data dissemination is essential for advancements in genetics, but also brings to light concerns regarding privacy.\nC_LIO_LIPrivacy breaching techniques work by cross-referencing two or more pieces of information to gain new, potentially undesirable knowledge on individuals or their families.\nC_LIO_LIBroadly speaking, the main routes to breach privacy are identity tracing, attribute disclosure, and completion of sensitive DNA information.\nC_LIO_LIIdentity tracing exploits quasi-identifiers in the DNA data or metadata to uncover the identity of an unknown genetic dataset.\nC_LIO_LIAttribute disclosure techniques work on known DNA datasets. They use the DNA information to link the identity of a person with a sensitive phenotype.\nC_LIO_LICompletion techniques also work on known DNA data. They try to uncover sensitive genomic areas that were masked to protect the participant.\nC_LIO_LIIn the last few years, we have witnessed a rapid growth in the range of techniques and tools to conduct these privacy-breaching attacks. Currently, most of the techniques are beyond the reach of the general public, but can be executed by trained persons with varying degrees of effort.\nC_LIO_LIThere is considerable debate regarding risk management. One camp supports a pragmatic, ad-hoc approach of privacy by obscurity and the other supports a systematic, mathematically-backed approach of privacy by design.\nC_LIO_LIPrivacy by design algorithms include access control, differential privacy, and cryptographic techniques. So far, data custodians of genetic databases mainly adopted access control as a mitigation strategy.\nC_LIO_LINew developments in cryptographic techniques may usher in an additional arsenal of security by design techniques.\nC_LI

10.1038/nrg3723

biorxiv

10.1101/000802

Generation of high-resolution a priori Y-chromosome phylogenies using &amp;#147;next-generation&amp;#148; sequencing data

Gregory R Magoon;Raymond H Banks;Christian Rottensteiner;Bonnie E Schrack;Vincent O Tilroe;Terry Robb;Andrew J Grierson;

Gregory R Magoon

Aerodyne Research, Inc.

2013-11-22

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/11/22/000802.source.xml

An approach for generating high-resolution a priori maximum parsimony Y-chromosome (chrY) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (next-generation) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which \"no-calls\" (through lack of mapped reads or otherwise) at particular site precludes a precise placement of the mutation. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and \"heterozygous\" genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if singletons are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the trunk of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are examined.

biorxiv

10.1101/000802

Generation of high-resolution a priori Y-chromosome phylogenies using &amp;#147;next-generation&amp;#148; sequencing data

Gregory R Magoon;Raymond H Banks;Christian Rottensteiner;Bonnie E Schrack;Vincent O Tilroe;Terry Robb;Andrew J Grierson;

Gregory R Magoon

Aerodyne Research, Inc.

2013-11-22

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/11/22/000802.source.xml

An approach for generating high-resolution a priori maximum parsimony Y-chromosome (chrY) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (next-generation) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which \"no-calls\" (through lack of mapped reads or otherwise) at particular site precludes a precise placement of the mutation. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and \"heterozygous\" genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if singletons are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the trunk of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are examined.

biorxiv

10.1101/000802

Generation of high-resolution a priori Y-chromosome phylogenies using &amp;#147;next-generation&amp;#148; sequencing data

Gregory R Magoon;Raymond H Banks;Christian Rottensteiner;Bonnie E Schrack;Vincent O Tilroe;Terry Robb;Andrew J Grierson;

Gregory R Magoon

Aerodyne Research, Inc.

2013-11-24

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/11/24/000802.source.xml

An approach for generating high-resolution a priori maximum parsimony Y-chromosome (chrY) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (next-generation) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which \"no-calls\" (through lack of mapped reads or otherwise) at particular site precludes a precise placement of the mutation. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and \"heterozygous\" genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if singletons are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the trunk of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are examined.

biorxiv

10.1101/000802

Generation of high-resolution a priori Y-chromosome phylogenies using &amp;#147;next-generation&amp;#148; sequencing data

Gregory R Magoon;Raymond H Banks;Christian Rottensteiner;Bonnie E Schrack;Vincent O Tilroe;Terry Robb;Andrew J Grierson;

Gregory R Magoon

Aerodyne Research, Inc.

2013-12-12

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/12/12/000802.source.xml

An approach for generating high-resolution a priori maximum parsimony Y-chromosome (chrY) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (next-generation) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which \"no-calls\" (through lack of mapped reads or otherwise) at particular site precludes a precise placement of the mutation. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and \"heterozygous\" genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if singletons are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the trunk of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are examined.

biorxiv

10.1101/000802

Generation of high-resolution a priori Y-chromosome phylogenies using &amp;#147;next-generation&amp;#148; sequencing data

Gregory R Magoon;Raymond H Banks;Christian Rottensteiner;Bonnie E Schrack;Vincent O Tilroe;Terry Robb;Andrew J Grierson;

Gregory R Magoon

Aerodyne Research, Inc.

2013-12-13

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/12/13/000802.source.xml

An approach for generating high-resolution a priori maximum parsimony Y-chromosome (chrY) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (next-generation) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which \"no-calls\" (through lack of mapped reads or otherwise) at particular site precludes a precise placement of the mutation. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and \"heterozygous\" genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if singletons are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the trunk of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are examined.

biorxiv

10.1101/001388

Bayesian inference of infectious disease transmission from whole genome sequence data

Xavier Didelot;Jennifer Gardy;Caroline Colijn;

Xavier Didelot

Imperial College London

2013-12-16

New Results

cc_by_nc_nd

Genomics

https://www.biorxiv.org/content/early/2013/12/16/001388.source.xml

Genomics is increasingly being used to investigate disease outbreaks, but an important question remains unanswered - how well do genomic data capture known transmission events, particularly for pathogens with long carriage periods or large within-host population sizes? Here we present a novel Bayesian approach to reconstruct densely-sampled outbreaks from genomic data whilst considering within-host diversity. We infer a time-labelled phylogeny using BEAST, then infer a transmission network via a Monte-Carlo Markov Chain. We find that under a realistic model of within-host evolution, reconstructions of simulated outbreaks contain substantial uncertainty even when genomic data reflect a high substitution rate. Reconstruction of a real-world tuberculosis outbreak displayed similar uncertainty, although the correct source case and several clusters of epidemiologically linked cases were identified. We conclude that genomics cannot wholly replace traditional epidemiology, but that Bayesian reconstructions derived from sequence data may form a useful starting point for a genomic epidemiology investigation.

10.1093/molbev/msu121

biorxiv

10.1101/001479

Massively differential bias between two widely used Illumina library preparation methods for small RNA sequencing

Jeanette Baran-Gale;Michael R Erdos;Christina Sison;Alice Young;Emily E Fannin;Peter S Chines;Praveen Sethupathy;

Praveen Sethupathy

University of North Carolina at Chapel HIll

2013-12-19

Confirmatory Results

cc_by_nc_nd

Genomics

https://www.biorxiv.org/content/early/2013/12/19/001479.source.xml

Recent advances in sequencing technology have helped unveil the unexpected complexity and diversity of small RNAs. A critical step in small RNA library preparation for sequencing is the ligation of adapter sequences to both the 5 and 3 ends of small RNAs. Two widely used protocols for small RNA library preparation, Illumina v1.5 and Illumina TruSeq, use different pairs of adapter sequences. In this study, we compare the results of small RNA-sequencing between v1.5 and TruSeq and observe a striking differential bias. Nearly 100 highly expressed microRNAs (miRNAs) are >5-fold differentially detected and 48 miRNAs are >10-fold differentially detected between the two methods of library preparation. In fact, some miRNAs, such as miR-24-3p, are over 30-fold differentially detected. The results are reproducible across different sequencing centers (NIH and UNC) and both major Illumina sequencing platforms, GAIIx and HiSeq. While some level of bias in library preparation is not surprising, the apparent massive differential bias between these two widely used adapter sets is not well appreciated. As increasingly more laboratories transition to the newer TruSeq-based library preparation for small RNAs, researchers should be aware of the extent to which the results may differ from previously published results using v1.5.

10.3389/fgene.2015.00352

biorxiv

10.1101/001511

The causal meaning of genomic predictors and how it affects the construction and comparison of genome-enabled selection models

Bruno D Valente;Gota Morota;Guilherme JM Rosa;Daniel Gianola;Kent Weigel;

Bruno D Valente

University of Wisconsin - Madison

2013-12-21

New Results

cc_no

Genomics

https://www.biorxiv.org/content/early/2013/12/21/001511.source.xml

The additive genetic effect is arguably the most important quantity inferred in animal and plant breeding analyses. The term effect indicates that it represents causal information, which is different from standard statistical concepts as regression coefficient and association. The process of inferring causal information is also different from standard statistical learning, as the former requires causal (i.e. non-statistical) assumptions and involves extra complexities. Remarkably, the task of inferring genetic effects is largely seen as a standard regression/prediction problem, contradicting its label. This widely accepted analysis approach is by itself insufficient for causal learning, suggesting that causality is not the point for selection. Given this incongruence, it is important to verify if genomic predictors need to represent causal effects to be relevant for selection decisions, especially because applying regression studies to answer causal questions may lead to wrong conclusions. The answer to this question defines if genomic selection models should be constructed aiming maximum genomic predictive ability or aiming identifiability of genetic causal effects. Here, we demonstrate that selection relies on a causal effect from genotype to phenotype, and that genomic predictors are only useful for selection if they distinguish such effect from other sources of association. Conversely, genomic predictors capturing non-causal signals provide information that is less relevant for selection regardless of the resulting predictive ability. Focusing on covariate choice decision, simulated examples are used to show that predictive ability, which is the criterion normally used to compare models, may not indicate the quality of genomic predictors for selection. Additionally, we propose using alternative criteria to construct models aiming for the identification of the genetic causal effects.

10.1534/genetics.114.169490

biorxiv

10.1101/000026

A Population Genetic Signature of Polygenic Local Adaptation

Jeremy J Berg;Graham Coop;

Graham Coop

University of California, Davis

2013-11-07

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2013/11/07/000026.source.xml

Adaptation in response to selection on polygenic phenotypes occurs via subtle allele frequencies shifts at many loci. Current population genomic techniques are not well posed to identify such signals. In the past decade, detailed knowledge about the specific loci underlying polygenic traits has begun to emerge from genome-wide association studies (GWAS). Here we combine this knowledge from GWAS with robust population genetic modeling to identify traits that have undergone local adaptation. Using GWAS data, we estimate the mean additive genetic value for a give phenotype across many populations as simple weighted sums of allele frequencies. We model the expected differentiation of GWAS loci among populations under neutrality to develop simple tests of selection across an arbitrary number of populations with arbitrary population structure. To find support for the role of specific environmental variables in local adaptation we test for correlations with the estimated genetic values. We also develop a general test of local adaptation to identify overdispersion of the estimated genetic values values among populations. This test is a natural generalization of QST /FST comparisons based on GWAS predictions. Finally we lay out a framework to identify the individual populations or groups of populations that contribute to the signal of overdispersion. These tests have considerably greater power than their single locus equivalents due to the fact that they look for positive covariance between like effect alleles. We apply our tests to the human genome diversity panel dataset using GWAS data for six different traits. This analysis uncovers a number of putative signals of local adaptation, and we discuss the biological interpretation and caveats of these results.

10.1371/journal.pgen.1004412

biorxiv

10.1101/000026

A Population Genetic Signature of Polygenic Local Adaptation

Jeremy J Berg;Graham Coop;

Graham Coop

University of California, Davis

2014-09-08

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2014/09/08/000026.source.xml

Adaptation in response to selection on polygenic phenotypes occurs via subtle allele frequencies shifts at many loci. Current population genomic techniques are not well posed to identify such signals. In the past decade, detailed knowledge about the specific loci underlying polygenic traits has begun to emerge from genome-wide association studies (GWAS). Here we combine this knowledge from GWAS with robust population genetic modeling to identify traits that have undergone local adaptation. Using GWAS data, we estimate the mean additive genetic value for a give phenotype across many populations as simple weighted sums of allele frequencies. We model the expected differentiation of GWAS loci among populations under neutrality to develop simple tests of selection across an arbitrary number of populations with arbitrary population structure. To find support for the role of specific environmental variables in local adaptation we test for correlations with the estimated genetic values. We also develop a general test of local adaptation to identify overdispersion of the estimated genetic values values among populations. This test is a natural generalization of QST /FST comparisons based on GWAS predictions. Finally we lay out a framework to identify the individual populations or groups of populations that contribute to the signal of overdispersion. These tests have considerably greater power than their single locus equivalents due to the fact that they look for positive covariance between like effect alleles. We apply our tests to the human genome diversity panel dataset using GWAS data for six different traits. This analysis uncovers a number of putative signals of local adaptation, and we discuss the biological interpretation and caveats of these results.

10.1371/journal.pgen.1004412

biorxiv

10.1101/000257

Matchmaker, Matchmaker, Make Me a Match: Migration of Populations via Marriages in the Past

Sang Hoon Lee;Robyn Ffrancon;Daniel M. Abrams;Beom Jun Kim;Mason A. Porter;

Sang Hoon Lee

Sungkyunkwan University

2013-11-12

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2013/11/12/000257.source.xml

The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data--including banknote flows, mobile phone records, and transportation data--have led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present such an analysis: we demonstrate that the data record from Korean family books (called \"jokbo\") can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the \"ergodicity\" of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration patterns in Korea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.

10.1103/PhysRevX.4.041009

biorxiv

10.1101/000257

Matchmaker, Matchmaker, Make Me a Match: Migration of Populations via Marriages in the Past

Sang Hoon Lee;Robyn Ffrancon;Daniel M. Abrams;Beom Jun Kim;Mason A. Porter;

Sang Hoon Lee

Sungkyunkwan University

2014-05-27

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/05/27/000257.source.xml

The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data--including banknote flows, mobile phone records, and transportation data--have led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present such an analysis: we demonstrate that the data record from Korean family books (called \"jokbo\") can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the \"ergodicity\" of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration patterns in Korea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.

10.1103/PhysRevX.4.041009

biorxiv

10.1101/000257

Matchmaker, Matchmaker, Make Me a Match: Migration of Populations via Marriages in the Past

Sang Hoon Lee;Robyn Ffrancon;Daniel M. Abrams;Beom Jun Kim;Mason A. Porter;

Sang Hoon Lee

Sungkyunkwan University

2014-08-16

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/08/16/000257.source.xml

The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data--including banknote flows, mobile phone records, and transportation data--have led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present such an analysis: we demonstrate that the data record from Korean family books (called \"jokbo\") can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the \"ergodicity\" of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration patterns in Korea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.

10.1103/PhysRevX.4.041009

biorxiv

10.1101/000257

Matchmaker, Matchmaker, Make Me a Match: Migration of Populations via Marriages in the Past

Sang Hoon Lee;Robyn Ffrancon;Daniel M. Abrams;Beom Jun Kim;Mason A. Porter;

Sang Hoon Lee

Sungkyunkwan University

2014-10-16

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/10/16/000257.source.xml

The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data--including banknote flows, mobile phone records, and transportation data--have led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present such an analysis: we demonstrate that the data record from Korean family books (called \"jokbo\") can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the \"ergodicity\" of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration patterns in Korea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.

10.1103/PhysRevX.4.041009

biorxiv

10.1101/000414

The evolution of sex differences in disease genetics

William P Gilks;Jessica K Abbott;Edward H Morrow;

Jessica K Abbott

Lund University

2013-11-14

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2013/11/14/000414.source.xml

There are significant differences in the biology of males and females, ranging from biochemical pathways to behavioural responses, which are relevant to modern medicine. Broad-sense heritability estimates differ between the sexes for many common medical disorders, indicating that genetic architecture can be sex-dependent. Recent genome-wide association studies (GWAS) have successfully identified sex-specific and sex-biased effects, where in addition to sex-specific effects on gene expression, twenty-two medical traits have sex-specific or sex-biased loci. Sex-specific genetic architecture of complex traits is also extensively documented in model organisms using genome-wide linkage or association mapping, and in gene disruption studies. The evolutionary origins of sex-specific genetic architecture and sexual dimorphism lie in the fact that males and females share most of their genetic variation yet experience different selection pressures. At the extreme is sexual antagonism, where selection on an allele acts in opposite directions between the sexes. Sexual antagonism has been repeatedly identified via a number of experimental methods in a range of different taxa. Although the molecular basis remains to be identified, mathematical models predict the maintenance of deleterious variants that experience selection in a sex-dependent manner. There are multiple mechanisms by which sexual antagonism and alleles under sex-differential selection could contribute toward the genetics of common, complex disorders. The evidence we review clearly indicates that further research into sex-dependent selection and the sex-specific genetic architecture of diseases would be rewarding. This would be aided by studies of laboratory and wild animal populations, and by modelling sex-specific effects in genome-wide association data with joint, gene-by-sex interaction tests. We predict that even sexually monomorphic diseases may harbour cryptic sex-specific genetic architecture. Furthermore, empirical evidence suggests that investigating sex-dependent epistasis may be especially rewarding. Finally, the prevalent nature of sex-specific genetic architecture in disease offers scope for the development of more effective, sex-specific therapies.\n\nFundingThis work was supported by the European Research Council (WPG and EHM; Starting Grant #280632), a Royal Society University Research Fellowship (EHM), the Swedish Research Council (JKA), and the Volkswagen Foundation (JKA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting interestsThe authors declare that they have no competing financial interests.

10.1016/j.tig.2014.08.006

biorxiv

10.1101/000687

Human genetics and clinical aspects of neurodevelopmental disorders

Gholson J Lyon;Jason O'Rawe;

Gholson J Lyon

CSHL

2013-11-18

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2013/11/18/000687.source.xml

Introduction Introduction Clinical classifications and the... De novo mutations, germline... Rare and compensatory mutations Current ability / approaches Prenatal diagnosis,... Implications for acceptance,... Conclusions References \"our incomplete studies do not permit actual classification; but it is better to leave things by themselves rather than to force them into classes which have their foundation only on paper\" -- Edouard Seguin (Seguin, 1866)\n\n\"The fundamental mistake which vitiates all work based upon Mendels method is the neglect of ancestry, and the attempt to regard the whole effect upon offspring, produced by a particular parent, as due to the existence in the parent of particular structural c ...

biorxiv

10.1101/000687

Human genetics and clinical aspects of neurodevelopmental disorders

Gholson J Lyon;Jason O'Rawe;

Gholson J Lyon

CSHL

2014-02-20

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2014/02/20/000687.source.xml

Introduction Introduction Clinical classifications and the... De novo mutations, germline... Rare and compensatory mutations Current ability / approaches Prenatal diagnosis,... Implications for acceptance,... Conclusions References \"our incomplete studies do not permit actual classification; but it is better to leave things by themselves rather than to force them into classes which have their foundation only on paper\" -- Edouard Seguin (Seguin, 1866)\n\n\"The fundamental mistake which vitiates all work based upon Mendels method is the neglect of ancestry, and the attempt to regard the whole effect upon offspring, produced by a particular parent, as due to the existence in the parent of particular structural c ...

biorxiv

10.1101/000687

Human genetics and clinical aspects of neurodevelopmental disorders

Gholson J Lyon;Jason O'Rawe;

Gholson J Lyon

CSHL

2014-06-22

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2014/06/22/000687.source.xml

Introduction Introduction Clinical classifications and the... De novo mutations, germline... Rare and compensatory mutations Current ability / approaches Prenatal diagnosis,... Implications for acceptance,... Conclusions References \"our incomplete studies do not permit actual classification; but it is better to leave things by themselves rather than to force them into classes which have their foundation only on paper\" -- Edouard Seguin (Seguin, 1866)\n\n\"The fundamental mistake which vitiates all work based upon Mendels method is the neglect of ancestry, and the attempt to regard the whole effect upon offspring, produced by a particular parent, as due to the existence in the parent of particular structural c ...

biorxiv

10.1101/000687

Human genetics and clinical aspects of neurodevelopmental disorders

Gholson J Lyon;Jason O'Rawe;

Gholson J Lyon

CSHL

2014-10-06

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2014/10/06/000687.source.xml

Introduction Introduction Clinical classifications and the... De novo mutations, germline... Rare and compensatory mutations Current ability / approaches Prenatal diagnosis,... Implications for acceptance,... Conclusions References \"our incomplete studies do not permit actual classification; but it is better to leave things by themselves rather than to force them into classes which have their foundation only on paper\" -- Edouard Seguin (Seguin, 1866)\n\n\"The fundamental mistake which vitiates all work based upon Mendels method is the neglect of ancestry, and the attempt to regard the whole effect upon offspring, produced by a particular parent, as due to the existence in the parent of particular structural c ...

biorxiv

10.1101/001073

Variational Inference of Population Structure in Large SNP Datasets

Anil Raj;Matthew Stephens;Jonathan K Pritchard;

Anil Raj

Stanford University

2013-12-02

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2013/12/02/001073.source.xml

Tools for estimating population structure from genetic data are now used in a wide variety of applications in population genetics. However, inferring population structure in large modern data sets imposes severe computational challenges. Here, we develop efficient algorithms for approximate inference of the model underlying the STRUCTURE program using a variational Bayesian framework. Variational methods pose the problem of computing relevant posterior distributions as an optimization problem, allowing us to build on recent advances in optimization theory to develop fast inference tools. In addition, we propose useful heuristic scores to identify the number of populations represented in a dataset and a new hierarchical prior to detect weak population structure in the data. We test the variational algorithms on simulated data, and illustrate using genotype data from the CEPH-Human Genome Diversity Panel. The variational algorithms are almost two orders of magnitude faster than STRUCTURE and achieve accuracies comparable to those of ADMIXTURE. Furthermore, our results show that the heuristic scores for choosing model complexity provide a reasonable range of values for the number of populations represented in the data, with minimal bias towards detecting structure when it is very weak. Our algorithm, fastSTRUCTURE, is freely available online at http://pritchardlab.stanford.edu/structure.html.

10.1534/genetics.114.164350

biorxiv

10.1101/001099

OTX2 Dosage Sensitivity is Implicated in Hemifacial Microsomia

Dina Zielinski;Barak Markus;Mona Sheikh;Melissa Gymrek;Clement Chu;Marta Zaks;Balaji Srinivasan;Jodi D. Hoffman;Dror Aizenbud;Yaniv Erlich;

Yaniv Erlich

Whitehead Institute

2013-12-03

New Results

cc_by

Genetics

https://www.biorxiv.org/content/early/2013/12/03/001099.source.xml

Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. Here, we investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. We performed whole-exome sequencing and a genome-wide survey of segmental variations. Analysis of the exome sequencing results indicated the absence of a pathogenic coding point mutation. Inspection of segmental variations identified a 1.3Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is concordant with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of our study. Our findings highlight dosage sensitivity of OTX2 in human craniofacial development and suggest a possible shared etiology between a subtype of hemifacial microsomia and medulloblastoma.

10.1371/journal.pone.0096788

biorxiv

10.1101/001354

A Tale of Two Hypotheses: Genetics and the Ethnogenesis of Ashkenazi Jewry

Aram Yardumian;

Aram Yardumian

University of Pennsylvania

2013-12-12

Contradictory Results

cc_no

Genetics

https://www.biorxiv.org/content/early/2013/12/12/001354.source.xml

The debate over the ethnogenesis of Ashkenazi Jewry is longstanding, and has been hampered by a lack of Jewish historiographical work between the Biblical and the early Modern eras. Most historians, as well as geneticists, situate them as the descendants of Israelite tribes whose presence in Europe is owed to deportations during the Roman conquest of Palestine, as well as migration from Babylonia, and eventual settlement along the Rhine. By contrast, a few historians and other writers, most famously Arthur Koestler, have looked to migrations following the decline of the little-understood Medieval Jewish kingdom of Khazaria as the main source for Ashkenazi Jewry. A recent study of genetic variation in southeastern European populations (Elhaik 2012) also proposed a Khazarian origin for Ashkenazi Jews, eliciting considerable criticism from other scholars investigating Jewish ancestry who favor a Near Eastern origin of Ashkenazi populations. This paper re-examines the genetic data and analytical approaches used in these studies of Jewish ancestry, and situates them in the context of historical, linguistic, and archaeological evidence from the Caucasus, Europe and the Near East. Based on this reanalysis, it appears not only that the Khazar Hypothesis per se is without serious merit, but also the veracity of the Rhineland Hypothesis may also be questionable.

biorxiv

10.1101/001453

Selection signatures in worldwide Sheep populations

Maria-Ines Fariello;Bertrand Servin;Gwenola Tosser-Klopp;Rachelle Rupp;Carole Moreno;International Sheep Genomics Consortium n.a.;Magali San Cristobal;simon boitard;

simon boitard

INRA

2013-12-17

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2013/12/17/001453.source.xml

The diversity of populations in domestic species offer great opportunities to study genome response to selection. The recently published Sheep Hapmap dataset is a great example of characterization of the world wide genetic diversity in the Sheep. In this study, we re-analyzed the Sheep Hapmap dataset to identify selection signatures in worldwide Sheep populations. Compared to previous analyses, we make use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of Linkage Disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows to pinpoint several new selection signatures in the sheep genome and to distinguish those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the one previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments.

10.1371/journal.pone.0103813

biorxiv

10.1101/001453

Selection signatures in worldwide Sheep populations

Maria-Ines Fariello;Bertrand Servin;Gwenola Tosser-Klopp;Rachelle Rupp;Carole Moreno;International Sheep Genomics Consortium n.a.;Magali San Cristobal;simon boitard;

simon boitard

INRA

2014-04-11

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/04/11/001453.source.xml

The diversity of populations in domestic species offer great opportunities to study genome response to selection. The recently published Sheep Hapmap dataset is a great example of characterization of the world wide genetic diversity in the Sheep. In this study, we re-analyzed the Sheep Hapmap dataset to identify selection signatures in worldwide Sheep populations. Compared to previous analyses, we make use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of Linkage Disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows to pinpoint several new selection signatures in the sheep genome and to distinguish those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the one previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments.

10.1371/journal.pone.0103813

biorxiv

10.1101/001552

Ancient human genomes suggest three ancestral populations for present-day Europeans

Iosif Lazaridis;Nick Patterson;Alissa Mittnik;Gabriel Renaud;Swapan Mallick;Karola Kirsanow;Peter H. Sudmant;Joshua G. Schraiber;Sergi Castellano;Mark Lipson;Bonnie Berger;Christos Economou;Ruth Bollongino;Qiaomei Fu;Kirsten Bos;Susanne Nordenfelt;Heng Li;Cesare de Filippo;Kay Prüfer;Susanna Sawyer;Cosimo Posth;Wolfgang Haak;Fredrik Hallgren;Elin Fornander;Nadin Rohland;Dominique Delsate;Michael Francken;Jean-Michel Guinet;Joachim Wahl;George Ayodo;Hamza A. Babiker;Graciela Baillet;Elena Balanovska;Oleg Balanovsky;Ramiro Barrantes;Gabriel Bedoya;Haim Ben-Ami;Judit Bene;Fouad Berrada;Claudio M.

Johannes Krause

Institute for Archaeological Sciences, University of Tübingen

2013-12-23

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2013/12/23/001552.source.xml

We sequenced genomes from a [~]7,000 year old early farmer from Stuttgart in Germany, an [~]8,000 year old hunter-gatherer from Luxembourg, and seven [~]8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had [~]44% ancestry from a \"Basal Eurasian\" lineage that split prior to the diversification of all other non-African lineages.

10.1038/nature13673

biorxiv

10.1101/001552

Ancient human genomes suggest three ancestral populations for present-day Europeans

Iosif Lazaridis;Nick Patterson;Alissa Mittnik;Gabriel Renaud;Swapan Mallick;Karola Kirsanow;Peter H. Sudmant;Joshua G. Schraiber;Sergi Castellano;Mark Lipson;Bonnie Berger;Christos Economou;Ruth Bollongino;Qiaomei Fu;Kirsten Bos;Susanne Nordenfelt;Heng Li;Cesare de Filippo;Kay Prüfer;Susanna Sawyer;Cosimo Posth;Wolfgang Haak;Fredrik Hallgren;Elin Fornander;Nadin Rohland;Dominique Delsate;Michael Francken;Jean-Michel Guinet;Joachim Wahl;George Ayodo;Hamza A. Babiker;Graciela Baillet;Elena Balanovska;Oleg Balanovsky;Ramiro Barrantes;Gabriel Bedoya;Haim Ben-Ami;Judit Bene;Fouad Berrada;Claudio M.

Johannes Krause

Institute for Archaeological Sciences, University of Tübingen

2014-04-02

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/04/02/001552.source.xml

We sequenced genomes from a [~]7,000 year old early farmer from Stuttgart in Germany, an [~]8,000 year old hunter-gatherer from Luxembourg, and seven [~]8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had [~]44% ancestry from a \"Basal Eurasian\" lineage that split prior to the diversification of all other non-African lineages.

10.1038/nature13673

biorxiv

10.1101/001552

Ancient human genomes suggest three ancestral populations for present-day Europeans

Iosif Lazaridis;Nick Patterson;Alissa Mittnik;Gabriel Renaud;Swapan Mallick;Karola Kirsanow;Peter H. Sudmant;Joshua G. Schraiber;Sergi Castellano;Mark Lipson;Bonnie Berger;Christos Economou;Ruth Bollongino;Qiaomei Fu;Kirsten Bos;Susanne Nordenfelt;Heng Li;Cesare de Filippo;Kay Prüfer;Susanna Sawyer;Cosimo Posth;Wolfgang Haak;Fredrik Hallgren;Elin Fornander;Nadin Rohland;Dominique Delsate;Michael Francken;Jean-Michel Guinet;Joachim Wahl;George Ayodo;Hamza A. Babiker;Graciela Baillet;Elena Balanovska;Oleg Balanovsky;Ramiro Barrantes;Gabriel Bedoya;Haim Ben-Ami;Judit Bene;Fouad Berrada;Claudio M.

Johannes Krause

Institute for Archaeological Sciences, University of Tübingen

2014-04-02

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/04/02/001552.source.xml

We sequenced genomes from a [~]7,000 year old early farmer from Stuttgart in Germany, an [~]8,000 year old hunter-gatherer from Luxembourg, and seven [~]8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had [~]44% ancestry from a \"Basal Eurasian\" lineage that split prior to the diversification of all other non-African lineages.

10.1038/nature13673

biorxiv

10.1101/001552

Ancient human genomes suggest three ancestral populations for present-day Europeans

Iosif Lazaridis;Nick Patterson;Alissa Mittnik;Gabriel Renaud;Swapan Mallick;Karola Kirsanow;Peter H. Sudmant;Joshua G. Schraiber;Sergi Castellano;Mark Lipson;Bonnie Berger;Christos Economou;Ruth Bollongino;Qiaomei Fu;Kirsten Bos;Susanne Nordenfelt;Heng Li;Cesare de Filippo;Kay Prüfer;Susanna Sawyer;Cosimo Posth;Wolfgang Haak;Fredrik Hallgren;Elin Fornander;Nadin Rohland;Dominique Delsate;Michael Francken;Jean-Michel Guinet;Joachim Wahl;George Ayodo;Hamza A. Babiker;Graciela Baillet;Elena Balanovska;Oleg Balanovsky;Ramiro Barrantes;Gabriel Bedoya;Haim Ben-Ami;Judit Bene;Fouad Berrada;Claudio M.

Johannes Krause

Institute for Archaeological Sciences, University of Tübingen

2014-04-05

New Results

cc_by_nc_nd

Genetics

https://www.biorxiv.org/content/early/2014/04/05/001552.source.xml

We sequenced genomes from a [~]7,000 year old early farmer from Stuttgart in Germany, an [~]8,000 year old hunter-gatherer from Luxembourg, and seven [~]8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had [~]44% ancestry from a \"Basal Eurasian\" lineage that split prior to the diversification of all other non-African lineages.

10.1038/nature13673

biorxiv

10.1101/001347

Evaluating the use of ABBA-BABA statistics to locate introgressed loci

Simon H. Martin;John W. Davey;Chris D. Jiggins;

Simon H. Martin

University of Cambridge

2013-12-11

New Results

cc_by

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/11/001347.source.xml

Several methods have been proposed to test for introgression across genomes. One method tests for a genome-wide excess of shared derived alleles between taxa using Pattersons D statistic, but does not establish which loci show such an excess or whether the excess is due to introgression or ancestral population structure. Several recent studies have extended the use of D by applying the statistic to small genomic regions, rather than genome-wide. Here, we use simulations and whole genome data from Heliconius butterflies to investigate the behavior of D in small genomic regions. We find that D is unreliable in this situation as it gives inflated values when effective population size is low, causing D outliers to cluster in genomic regions of reduced diversity. As an alternative, we propose a related statistic [Formula] a modified version of a statistic originally developed to estimate the genome-wide fraction of admixture. [Formula] is not subject to the same biases as D, and is better at identifying introgressed loci. Finally, we show that both D and [Formula] outliers tend to cluster in regions of low absolute divergence (dXY), which can confound a recently proposed test for differentiating introgression from shared ancestral variation at individual loci.

10.1093/molbev/msu269

biorxiv

10.1101/001347

Evaluating the use of ABBA-BABA statistics to locate introgressed loci

Simon H. Martin;John W. Davey;Chris D. Jiggins;

Simon H. Martin

University of Cambridge

2014-06-02

New Results

cc_by

Evolutionary Biology

https://www.biorxiv.org/content/early/2014/06/02/001347.source.xml

Several methods have been proposed to test for introgression across genomes. One method tests for a genome-wide excess of shared derived alleles between taxa using Pattersons D statistic, but does not establish which loci show such an excess or whether the excess is due to introgression or ancestral population structure. Several recent studies have extended the use of D by applying the statistic to small genomic regions, rather than genome-wide. Here, we use simulations and whole genome data from Heliconius butterflies to investigate the behavior of D in small genomic regions. We find that D is unreliable in this situation as it gives inflated values when effective population size is low, causing D outliers to cluster in genomic regions of reduced diversity. As an alternative, we propose a related statistic [Formula] a modified version of a statistic originally developed to estimate the genome-wide fraction of admixture. [Formula] is not subject to the same biases as D, and is better at identifying introgressed loci. Finally, we show that both D and [Formula] outliers tend to cluster in regions of low absolute divergence (dXY), which can confound a recently proposed test for differentiating introgression from shared ancestral variation at individual loci.

10.1093/molbev/msu269

biorxiv

10.1101/001347

Evaluating the use of ABBA-BABA statistics to locate introgressed loci

Simon H. Martin;John W. Davey;Chris D. Jiggins;

Simon H. Martin

University of Cambridge

2014-08-20

New Results

cc_by

Evolutionary Biology

https://www.biorxiv.org/content/early/2014/08/20/001347.source.xml

Several methods have been proposed to test for introgression across genomes. One method tests for a genome-wide excess of shared derived alleles between taxa using Pattersons D statistic, but does not establish which loci show such an excess or whether the excess is due to introgression or ancestral population structure. Several recent studies have extended the use of D by applying the statistic to small genomic regions, rather than genome-wide. Here, we use simulations and whole genome data from Heliconius butterflies to investigate the behavior of D in small genomic regions. We find that D is unreliable in this situation as it gives inflated values when effective population size is low, causing D outliers to cluster in genomic regions of reduced diversity. As an alternative, we propose a related statistic [Formula] a modified version of a statistic originally developed to estimate the genome-wide fraction of admixture. [Formula] is not subject to the same biases as D, and is better at identifying introgressed loci. Finally, we show that both D and [Formula] outliers tend to cluster in regions of low absolute divergence (dXY), which can confound a recently proposed test for differentiating introgression from shared ancestral variation at individual loci.

10.1093/molbev/msu269

biorxiv

10.1101/001404

The importance of population growth and regulation in human life history evolution

Ryan Baldini;

Ryan Baldini

UC Davis

2013-12-14

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/14/001404.source.xml

Explaining the evolution of human life history characteristics remains an outstanding problem to evolutionary anthropologists. Progress is hindered by common misunderstandings of how selection works in age-structured populations. I review two important results of life history theory related to demography. First, different life history strategies evolve under density-independent and density-dependent population growth. Second, and more poorly appreciated, different kinds of density-dependence also select for different life history strategies; assuming zero population growth alone is insufficient to determine the optimal strategy. I show that these facts are more than methodological niceties by reanalyzing the model by Kaplan et al. (2000) and showing that the results depend strongly on the form of population regulation assumed. This analysis suggests that progress in human life history theory requires better understanding of the demography of our ancestors. I close with a discussion of empirical implications.

10.1371/journal.pone.0119789

biorxiv

10.1101/001289

An Adaptive Threshold in Mammalian Neocortical Evolution

Eric Lewitus;Iva Kelava;Alex T Kalinka;Pavel Tomancak;Wieland B Huttner;

Wieland B Huttner

Max Planck Institute of Molecular Cell Biology and Genetics

2013-12-13

New Results

cc_no

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/13/001289.source.xml

Expansion of the neocortex is a hallmark of human evolution. However, it remains an open question what adaptive mechanisms facilitated its expansion. Here we show, using gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We provide evidence that the evolution of a highly folded neocortex, as observed in humans, requires the traversal of a threshold of [~]109 neurons, and that species above and below the threshold exhibit a bimodal distribution of physiological and life-history traits, establishing two phenotypic groups. We identify, using discrete mathematical models, proliferative divisions of pro-genitors in the basal compartment of the developing neocortex as evolutionarily necessary and sufficient for generating a fourteen-fold increase in daily prenatal neuron production and thus traversal of the neuronal threshold. Finally, using RNA-seq data from fetal human neocortical germinal zones, we show a genomic correlate to the neuron threshold in the differential conservation of long intergenic non-coding RNA. (see arXiv:1304.5412)

10.1371/journal.pbio.1002000

biorxiv

10.1101/001289

An Adaptive Threshold in Mammalian Neocortical Evolution

Eric Lewitus;Iva Kelava;Alex T Kalinka;Pavel Tomancak;Wieland B Huttner;

Wieland B Huttner

Max Planck Institute of Molecular Cell Biology and Genetics

2013-12-16

New Results

cc_no

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/16/001289.source.xml

Expansion of the neocortex is a hallmark of human evolution. However, it remains an open question what adaptive mechanisms facilitated its expansion. Here we show, using gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We provide evidence that the evolution of a highly folded neocortex, as observed in humans, requires the traversal of a threshold of [~]109 neurons, and that species above and below the threshold exhibit a bimodal distribution of physiological and life-history traits, establishing two phenotypic groups. We identify, using discrete mathematical models, proliferative divisions of pro-genitors in the basal compartment of the developing neocortex as evolutionarily necessary and sufficient for generating a fourteen-fold increase in daily prenatal neuron production and thus traversal of the neuronal threshold. Finally, using RNA-seq data from fetal human neocortical germinal zones, we show a genomic correlate to the neuron threshold in the differential conservation of long intergenic non-coding RNA. (see arXiv:1304.5412)

10.1371/journal.pbio.1002000

biorxiv

10.1101/001446

Direct Reciprocity Under Uncertainty Does Not Explain One-Shot Cooperation, But It Can Explain Norm Psychology

Matthew Zefferman;

Matthew R Zefferman

National Institute for Mathematical and Biological Synthesis

2013-12-17

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/17/001446.source.xml

Humans in many societies cooperate in economic experiments at much higher levels than would be expected if their goal was maximizing economic returns even when interactions are anonymous and one-shot. This is a puzzle because paying a cost to benefit another player in one-shot interactions has no direct benefit to the cooperator. This paper explores the logic of two competing evolutionary hypotheses to explain this behavior. The \"norm psychology\" hypothesis holds that a players choice of strategy is heavily influenced by socially-learned cultural norms. Its premise is that over the course of human evolutionary history, cultural norms varied considerably across human societies and through a process of gene-culture co-evolution, humans evolved mechanisms to learn and adopt the norms of their particular society. The \"evolutionary mismatch\" hypothesis holds that pro-social preferences evolved genetically in our hunter-gatherer past where one-shot anonymous interactions were rare and these evolved \"protocols\" for cooperation are misapplied in modern, laboratory, conditions. I compare these hypotheses by adopting a well-known model of the mismatch hypothesis. I show that the cooperation generated by the model is based on a flawed assumption - that the best thing to do is cooperate in a repeated game. I show that repeated games generate a great diversity of behavioral equilibria, in support of the norm psychology hypothesiss premise. When interaction is repeated, adopting local norms is a more evolutionarily successful strategy than automatically cooperating. If various groups are at different behavioral equilibria, then cultural selection between groups tends to select for cooperative behavior.

biorxiv

10.1101/001487

Hawkish but helpful: When cultural group selection favors within-group aggression

Ben Hanowell;

Ben Hanowell

Department of Anthropology, University of Washington

2013-12-20

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/20/001487.source.xml

The origin of cooperation is a central problem in evolutionary biology and social science. Cultural group selection and parochial altruism are popular but controversial evolutionary explanations for large-scale cooperation. Proponents of the cultural group selection hypothesis argue that the human tendency to conform--a consequence of our reliance on social learning--maintained sufficient between-group variation to allow group selection (which favors altruism) to overpower individual selection (which favors selfishness), whereupon large-scale altruism could emerge. Proponents of the parochial altruism hypothesis argue that altruism could emerge in tandem with hostility toward other groups if the combination of the two traits increased success in inter-group contests. Proponents of both hypotheses assume that cooperation is altruistic and that within-group conflict is antithetical to cooperation, implying that group selection for cooperation reduces within-group conflict. Yet within-group conflict need not be antithetical to cooperation. This essay uses a mathematical model to show that selection between groups can lead to greater within-group aggression if within-group aggression enhances the value of individually costly public goods contributions. This model may help to explain cross-cultural associations between warfare, socialization for aggression, aggressive sports, and interpersonal violence among humans. It may also apply to other forms of inter-group conflict among humans. Finally, the model suggests that group selection can lead to disharmony within groups, a caveat to the use of group selection models to inform social policy.

biorxiv

10.1101/001529

Revisiting the effect of population size on cumulative cultural evolution

Ryan Baldini;

Ryan Baldini

UC Davis

2013-12-21

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/21/001529.source.xml

Henrich (2004) argued that larger populations can better maintain complex technologies because they contain more highly skilled people whom others can imitate. His original model, however, did not distinguish the effects of population size from population density or network size; a learners social network included the entire population. Does population size remain important when populations are subdivided and networks are realistically small? I use a mathematical model to show that population size has little effect on equilibrium levels of mean skill under a wide range of conditions. The effects of network size and transmission error rate usually overshadow that of population size. Population size can, however, affect the rate at which a population approaches equilibrium, by increasing the rate at which innovations arise. This effect is small unless innovation is very rare. Whether population size predicts technological complexity in the real world, then, depends on whether technological evolution is innovation-limited and short of equilibrium. The effect of population \"connectedness,\" via migration or trade, is similar. I discuss the results of this analysis in light of the current empirical debate.

10.1163/15685373-12342153

biorxiv

10.1101/001529

Revisiting the effect of population size on cumulative cultural evolution

Ryan Baldini;

Ryan Baldini

UC Davis

2013-12-31

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/31/001529.source.xml

Henrich (2004) argued that larger populations can better maintain complex technologies because they contain more highly skilled people whom others can imitate. His original model, however, did not distinguish the effects of population size from population density or network size; a learners social network included the entire population. Does population size remain important when populations are subdivided and networks are realistically small? I use a mathematical model to show that population size has little effect on equilibrium levels of mean skill under a wide range of conditions. The effects of network size and transmission error rate usually overshadow that of population size. Population size can, however, affect the rate at which a population approaches equilibrium, by increasing the rate at which innovations arise. This effect is small unless innovation is very rare. Whether population size predicts technological complexity in the real world, then, depends on whether technological evolution is innovation-limited and short of equilibrium. The effect of population \"connectedness,\" via migration or trade, is similar. I discuss the results of this analysis in light of the current empirical debate.

10.1163/15685373-12342153

biorxiv

10.1101/001172

Species Delimitation using Genome-Wide SNP Data

Adam Leache;Matthew Fujita;Vladimir Minin;Remco Bouckaert;

Adam Leache

University of Washington

2013-12-05

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2013/12/05/001172.source.xml

The multi-species coalescent has provided important progress for evolutionary inferences, including increasing the statistical rigor and objectivity of comparisons among competing species delimitation models. However, Bayesian species delimitation methods typically require brute force integration over gene trees via Markov chain Monte Carlo (MCMC), which introduces a large computation burden and precludes their application to genomic-scale data. Here we combine a recently introduced dynamic programming algorithm for estimating species trees that bypasses MCMC integration over gene trees with sophisticated methods for estimating marginal likelihoods, needed for Bayesian model selection, to provide a rigorous and computationally tractable technique for genome-wide species delimitation. We provide a critical yet simple correction that brings the likelihoods of different species trees, and more importantly their corresponding marginal likelihoods, to the same common denominator, which enables direct and accurate comparisons of competing species delimitation models using Bayes factors. We test this approach, which we call Bayes factor delimitation (*with genomic data; BFD*), using common species delimitation scenarios with computer simulations. Varying the numbers of loci and the number of samples suggest that the approach can distinguish the true model even with few loci and limited samples per species. Misspecification of the prior for population size{theta} has little impact on support for the true model. We apply the approach to West African forest geckos (Hemidactylus fasciatus complex) using genome-wide SNP data data. This new Bayesian method for species delimitation builds on a growing trend for objective species delimitation methods with explicit model assumptions that are easily tested.

10.1093/sysbio/syu018

biorxiv

10.1101/001172

Species Delimitation using Genome-Wide SNP Data

Adam Leache;Matthew Fujita;Vladimir Minin;Remco Bouckaert;

Adam Leache

University of Washington

2014-01-04

New Results

cc_by_nc_nd

Evolutionary Biology

https://www.biorxiv.org/content/early/2014/01/04/001172.source.xml

The multi-species coalescent has provided important progress for evolutionary inferences, including increasing the statistical rigor and objectivity of comparisons among competing species delimitation models. However, Bayesian species delimitation methods typically require brute force integration over gene trees via Markov chain Monte Carlo (MCMC), which introduces a large computation burden and precludes their application to genomic-scale data. Here we combine a recently introduced dynamic programming algorithm for estimating species trees that bypasses MCMC integration over gene trees with sophisticated methods for estimating marginal likelihoods, needed for Bayesian model selection, to provide a rigorous and computationally tractable technique for genome-wide species delimitation. We provide a critical yet simple correction that brings the likelihoods of different species trees, and more importantly their corresponding marginal likelihoods, to the same common denominator, which enables direct and accurate comparisons of competing species delimitation models using Bayes factors. We test this approach, which we call Bayes factor delimitation (*with genomic data; BFD*), using common species delimitation scenarios with computer simulations. Varying the numbers of loci and the number of samples suggest that the approach can distinguish the true model even with few loci and limited samples per species. Misspecification of the prior for population size{theta} has little impact on support for the true model. We apply the approach to West African forest geckos (Hemidactylus fasciatus complex) using genome-wide SNP data data. This new Bayesian method for species delimitation builds on a growing trend for objective species delimitation methods with explicit model assumptions that are easily tested.

10.1093/sysbio/syu018

biorxiv

10.1101/000711

Sap flow through petioles and petioles reveals leaf-level responses to light and vapor pressure deficit in the tropical tree Tabebuia rosea (Bignoniaceae)

Adam Roddy;Klaus Winter;Todd Dawson;

Adam Roddy

University of California, Berkeley

2013-11-19

New Results

cc_by

Ecology

https://www.biorxiv.org/content/early/2013/11/19/000711.source.xml

Continuous measurements of sap flow have been widely used to measure water flux through tree stems and branches. However, these measurements lack the resolution necessary for determining fine-scale, leaf-level responses to environmental variables. We used the heat ratio method to measure sap flow rates through leaf petioles and leaflet petiolules of saplings of the tropical tree Tabebuia rosea (Bignoniaceae) to determine how leaf and leaflet sap flow responds to variation in light and vapor pressure deficit (VPD). We found that in the morning sap flow rates to east-facing leaves increased 26 minutes before adjacent west-facing leaves. Although leaves had higher integrated sap flow than their largest leaflet, this difference was not proportional to the difference in leaf area, which could be due to lower conduit area in petiolules than in petioles. In contrast to measurements on main stems, integrated daily sap flow was negatively correlated with daily mean VPD. Furthermore, leaves exhibited previously undescribed patterns of hysteresis in the sap flow-VPD and sap flow-PAR relationships. When hysteresis in the sap flow-PAR relationship was clockwise, the sap flow-VPD relationship was also clockwise; however, when hysteresis in the sap flow-PAR relationship was counterclockwise, the sap flow-VPD relationship displayed an intersected loop. These pattern differences highlight how substantially leaf-level processes may vary within a canopy and how leaf-level processes may not scale predictably to the stem level.

biorxiv

10.1101/000760

Linking indices for biodiversity monitoring to extinction risk theory

Michael A. McCarthy;Alana L. Moore;Jochen Krauss;John W Morgan;Christopher F. Clements;

Michael A. McCarthy

The University of Melbourne

2013-11-21

New Results

cc_no

Ecology

https://www.biorxiv.org/content/early/2013/11/21/000760.source.xml

Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. Here we develop three biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. The first index is based on the geometric mean abundance of species. A second uses a more general power mean. A third integrates both the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants, and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggests that the average extinction probability of birds has increased approximately 1% from 1970 to 2009.

10.1111/cobi.12308

biorxiv

10.1101/000760

Linking indices for biodiversity monitoring to extinction risk theory

Michael A. McCarthy;Alana L. Moore;Jochen Krauss;John W Morgan;Christopher F. Clements;

Michael A. McCarthy

The University of Melbourne

2014-02-07

New Results

cc_no

Ecology

https://www.biorxiv.org/content/early/2014/02/07/000760.source.xml

Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. Here we develop three biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. The first index is based on the geometric mean abundance of species. A second uses a more general power mean. A third integrates both the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants, and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggests that the average extinction probability of birds has increased approximately 1% from 1970 to 2009.

10.1111/cobi.12308

biorxiv

10.1101/000893

The Effectiveness of China’s National Forest Protection Program and National-level Nature Reserves, 2000 to 2010: PREPRINT

Guopeng Ren;Stephen S. Young;Lin Wang;Wei Wang;Yongcheng Long;Ruidong Wu;Junsheng Li;Jianguo Zhu;Douglas W. Yu;

Douglas W. Yu

Kunming Institute of Zoology

2013-11-25

New Results

cc_no

Ecology

https://www.biorxiv.org/content/early/2013/11/25/000893.source.xml

There is profound interest in knowing the degree to which Chinas institutions are capable of protecting its natural forests and biodiversity in the face of economic and political change. Chinas two most important forest protection policies are its National Forest Protection Program (NFPP) and its National-level Nature Reserves (NNRs). The NFPP was implemented in 17 provinces starting in the year 2000 in response to deforestation-caused flooding. We used MODIS data (MOD13Q1) to estimate forest cover and forest loss across mainland China, and we report that 1.765 million km2 or 18.7% of mainland China was covered in forest (12.3%, canopy cover > 70%) and woodland (6.4%, 40% [&le;] canopy cover < 70%) in 2000. By 2010, a total of 480,203 km2 of forest + woodland was lost, amounting to an annual deforestation rate of 2.7%. The forest-only loss was 127,473 km2, or 1.05% annually. The three most rapidly deforested provinces were outside NFPP jurisdiction, in the southeast. Within the NFPP provinces, the annual forest + woodland loss rate was 2.26%, and the forest-only rate was 0.62%. Because these loss rates are likely overestimates, China appears to have achieved, and even exceeded, its NFPP target of reducing deforestation to 1.1% annually in the target provinces. We also assemble the first-ever polygon dataset for Chinas forested NNRs (n = 237), which covered 74,030 km2 in 2000. Conventional unmatched and covariate-matching analyses both find that about two-thirds of Chinas NNRs exhibit effectiveness in protecting forest cover and that within-NNR deforestation rates are higher in provinces that have higher overall deforestation.

10.1111/cobi.12561

biorxiv

10.1101/001032

Mechanism of β-Aminobutyric Acid-Induced Resistance in Wheat to the Grain Aphid, Sitobion avenae

He-He Cao;Meng Zhang;Hui Zhao;Yi Zhang;Xing-Xing Wang;Shan-Shan Guo;Zhan-Feng Zhang;Tong-Xian Liu;

He-He Cao

Northwest A&F University

2013-12-02

New Results

cc_by_nc_nd

Ecology

https://www.biorxiv.org/content/early/2013/12/02/001032.source.xml

The non-protein amino acid {beta}-aminobutyric acid (BABA) could induce plant resistance to a broad spectrum of biotic and abiotic stresses. However, BABA-induced plant resistance to insects is less well-studied, especially its underlying mechanism. In this research, we applied BABA to wheat seedlings and tested its effects on Sitobion avenae. When applied as a soil drench, BABA significantly reduced weight of S. avenae, whereas foliar spray and seed treatment had no such effects. BABA-mediated suppression of S. avenae growth is dose dependent and could last at least for 7 days. The aminobutyric acid concentration in phloem sap of BABA-treated plants accumulated to high levels and increased with BABA concentrations applied. Moreover, after 10 days of treatment, the aminobutyric acid content in BABA-treated plants was still higher than that in control treatment. S. avenae could not discriminate artificial diet containing BABA from standard diet, indicating that BABA itself is not a deterrent to this aphid. Also S. avenae did not show preference for control plants or BABA-treated plants. Consistent with choice test results, S. avenae had similar feeding activities on control and BABA-treated plants, suggesting that BABA did not induce antifeedants in wheat seedlings. In addition, aminobutyric acid concentration in S. avenae feeding on BABA-treated plants was significantly higher than those feeding on control palnts. S. avenae growth rate was reduced on artificial diet containing BABA, indicating direct toxic effects of BABA to this aphid. These results suggest that BABA application could enhance wheat plant resistance to S. avenae and the mechanism is possibly due to direct toxicity of high BABA contents in plant phloem.

10.1371/journal.pone.0091768

biorxiv

10.1101/001263

Climate change triggers morphological and life-history evolution in response to predators

Edmund Hart;Nicholas Gotelli;

Edmund Hart

National Ecological Observatory Network

2013-12-10

New Results

cc_by_nc_nd

Ecology

https://www.biorxiv.org/content/early/2013/12/10/001263.source.xml

Although climate change is expected to reorganize entire communities, this restructuring might reflect either direct ecological or evolutionary responses to abiotic conditions or indirect effects mediated through altered species interactions. We tested the hypothesis that changes in trophic interaction strength due to altered predator abundance have a cascading evolutionary response in a prey species (Daphnia pulex). Using a multiyear / multigenerational field experiment, we manipulated 12 open aquatic mesocosms to simulate hydrological conditions under climate change. After a three-year press manipulation, we collected Daphnia pulex from each pond and raised them in a common garden. Using quantitative genetic methods, we measured a series of quantitative traits every other day on 108 individuals for eight weeks. There was a significant decrease in tail spine length and population growth rate in groups exposed to the most extreme future climate scenarios. Structural equation models demonstrated that trait changes were best explained as an indirect effect of climate change treatments mediated through changes in predator abundance. Our results suggest climate change can trigger a cascade of ecological and evolutionary forces by reducing predator density, which in turn acts as a selective force leading to evolutionary change in prey morphology and life history.

biorxiv

10.1101/001255

Broad-scale spatial patterns of canopy cover and pond morphology affect the structure of a Neotropical amphibian metacommunity

Diogo B. Provete;Thiago Gonçalves-Souza;Michel Garey;Itamar A. Martins;Denise Rossa-Feres;

Diogo B. Provete

Universidade Federal de Goiás

2013-12-10

New Results

cc_by_nc_nd

Ecology

https://www.biorxiv.org/content/early/2013/12/10/001255.source.xml

Spatial and environmental processes influence species composition at distinct scales. Previous studies suggested that the landscape-scale distribution of larval anurans is influenced by environmental gradients related to adult breeding site selection, such as pond canopy cover, but not water chemistry. However, the combined effects of spatial, pond morphology, and water chemistry variables on metacommunity structure of larval anurans have not been analyzed. We used a partial redundancy analysis with variation partitioning to analyze the relative influence of pond morphology (e.g., depth, area, and aquatic vegetation), water chemistry, and spatial variables on a tadpole metacommunity from southeastern Brazil. We predict that the metacommunity will be spatially structured at broad spatial scales, while environmental variables, mainly related to adult habitat selection, would play a larger role at fine spatial scales. We found that broad-scale spatial patterns of pond canopy cover and pond morphology strongly influenced metacommunity structure. Additionally, species composition was spatially autocorrelated at short distances. We suggest that the reproductive behavior of adult anurans is driving tadpole metacommunity dynamics, since pond morphology, but not water chemistry affects breeding site selection by adults. Our results contribute to the understanding of amphibian species diversity in tropical environments.

10.1007/s10750-014-1870-0

biorxiv

10.1101/001255

Broad-scale spatial patterns of canopy cover and pond morphology affect the structure of a Neotropical amphibian metacommunity

Diogo B. Provete;Thiago Gonçalves-Souza;Michel Garey;Itamar A. Martins;Denise Rossa-Feres;

Diogo B. Provete

Universidade Federal de Goiás

2014-04-09

New Results

cc_by_nc_nd

Ecology

https://www.biorxiv.org/content/early/2014/04/09/001255.source.xml

Spatial and environmental processes influence species composition at distinct scales. Previous studies suggested that the landscape-scale distribution of larval anurans is influenced by environmental gradients related to adult breeding site selection, such as pond canopy cover, but not water chemistry. However, the combined effects of spatial, pond morphology, and water chemistry variables on metacommunity structure of larval anurans have not been analyzed. We used a partial redundancy analysis with variation partitioning to analyze the relative influence of pond morphology (e.g., depth, area, and aquatic vegetation), water chemistry, and spatial variables on a tadpole metacommunity from southeastern Brazil. We predict that the metacommunity will be spatially structured at broad spatial scales, while environmental variables, mainly related to adult habitat selection, would play a larger role at fine spatial scales. We found that broad-scale spatial patterns of pond canopy cover and pond morphology strongly influenced metacommunity structure. Additionally, species composition was spatially autocorrelated at short distances. We suggest that the reproductive behavior of adult anurans is driving tadpole metacommunity dynamics, since pond morphology, but not water chemistry affects breeding site selection by adults. Our results contribute to the understanding of amphibian species diversity in tropical environments.

10.1007/s10750-014-1870-0

biorxiv

10.1101/001537

Assessing the Use of Antiviral Treatment to Control Influenza

Sarah C Kramer;Shweta Bansal;

Shweta Bansal

Georgetown University; National Institutes of Health

2013-12-26

New Results

cc_no

Ecology

https://www.biorxiv.org/content/early/2013/12/26/001537.source.xml

Vaccines are the cornerstone of influenza control policy, but can suffer from several drawbacks. Seasonal influenza vaccines are prone to production problems and low efficacies, while pandemic vaccines are unlikely to be available in time to slow a rapidly spreading global outbreak. Antiviral therapy was found to be beneficial during the influenza A(H1N1)pdm09 pandemic even with limited use; however, antiviral use has decreased further since then. We seek to determine the role antiviral therapy can play in pandemic and seasonal influenza control on the population level, and to find optimized strategies for more efficient use of treatment. Using an age-structured contact network model for an urban population, we find that while a conservative antiviral therapy strategy cannot replace a robust influenza vaccine, it can play a role in reducing attack rates and eliminating outbreaks.

10.1017/S0950268814002520

biorxiv

10.1101/001610

Black rhinoceros demography should be stage, not age, based.

Peter R Law;Wayne L Linklater;

Peter R Law

na

2013-12-30

New Results

cc_by_nc_nd

Ecology

https://www.biorxiv.org/content/early/2013/12/30/001610.source.xml

Biologically meaningful and standardized definitions of life stages are essential for demographic studies, especially for endangered and intensively managed species such as rhinoceros. Focusing on the black rhinoceros Diceros bicornis, we argue that standardized biological definitions of calf, subadult, and adult, rather than age classes, provide the appropriate basis for black rhinoceros demography. Age classes do not correlate well with the risks of mortality nor characterize, at least for females, the attainment of reproductive maturity. Black rhinoceros demography based on age classes, typical of existing literature, obscures the significance of studies of mortality and fecundity. Comparison of studies also requires standardized definitions. We propose biologically meaningful definitions of life stages appropriate for the demography of the black rhinoceros and encourage the community of rhinoceros researchers to reach consensus on standardized, demographically appropriate definitions for adoption for each rhinoceros species.

10.1111/aje.12148

biorxiv

10.1101/001677

Beyond species: why ecological interaction networks vary through space and time

Timothée Poisot;Daniel B Stouffer;Dominique Gravel;

Timothée Poisot

Université du Québec à Rimouski

2014-01-03

New Results

cc_by_nd

Ecology

https://www.biorxiv.org/content/early/2014/01/03/001677.source.xml

Community ecology is tasked with the considerable challenge of predicting the structure, and properties, of emerging ecosystems. It requires the ability to understand how and why species interact, as this will allow the development of mechanism-based predictive models, and as such to better characterize how ecological mechanisms act locally on the existence of interspecific interactions. Here we argue that the current conceptualization of species interaction networks is ill-suited for this task. Instead, we propose that future research must start to account for the intrinsic variability of species interactions, then scale up from here onto complex networks. This can be accomplished simply by recognizing that there exists intra-specific variability, in traits or properties related to the establishment of species interactions. By shifting the scale towards population-based processes, we show that this new approach will improve our predictive ability and mechanistic understanding of how species interact over large spatial or temporal scales.

10.1111/oik.01719

biorxiv

10.1101/001677

Beyond species: why ecological interaction networks vary through space and time

Timothée Poisot;Daniel B Stouffer;Dominique Gravel;

Timothée Poisot

Université du Québec à Rimouski

2014-01-04

New Results

cc_by_nd

Ecology

https://www.biorxiv.org/content/early/2014/01/04/001677.source.xml

Community ecology is tasked with the considerable challenge of predicting the structure, and properties, of emerging ecosystems. It requires the ability to understand how and why species interact, as this will allow the development of mechanism-based predictive models, and as such to better characterize how ecological mechanisms act locally on the existence of interspecific interactions. Here we argue that the current conceptualization of species interaction networks is ill-suited for this task. Instead, we propose that future research must start to account for the intrinsic variability of species interactions, then scale up from here onto complex networks. This can be accomplished simply by recognizing that there exists intra-specific variability, in traits or properties related to the establishment of species interactions. By shifting the scale towards population-based processes, we show that this new approach will improve our predictive ability and mechanistic understanding of how species interact over large spatial or temporal scales.

10.1111/oik.01719

biorxiv

10.1101/001677

Beyond species: why ecological interaction networks vary through space and time

Timothée Poisot;Daniel B Stouffer;Dominique Gravel;

Timothée Poisot

Université du Québec à Rimouski

2014-04-11

New Results

cc_by_nd

Ecology

https://www.biorxiv.org/content/early/2014/04/11/001677.source.xml

Community ecology is tasked with the considerable challenge of predicting the structure, and properties, of emerging ecosystems. It requires the ability to understand how and why species interact, as this will allow the development of mechanism-based predictive models, and as such to better characterize how ecological mechanisms act locally on the existence of interspecific interactions. Here we argue that the current conceptualization of species interaction networks is ill-suited for this task. Instead, we propose that future research must start to account for the intrinsic variability of species interactions, then scale up from here onto complex networks. This can be accomplished simply by recognizing that there exists intra-specific variability, in traits or properties related to the establishment of species interactions. By shifting the scale towards population-based processes, we show that this new approach will improve our predictive ability and mechanistic understanding of how species interact over large spatial or temporal scales.

10.1111/oik.01719

biorxiv

10.1101/001677

Beyond species: why ecological interaction networks vary through space and time

Timothée Poisot;Daniel B Stouffer;Dominique Gravel;

Timothée Poisot

Université du Québec à Rimouski

2014-07-21

New Results

cc_by

Ecology

https://www.biorxiv.org/content/early/2014/07/21/001677.source.xml

Community ecology is tasked with the considerable challenge of predicting the structure, and properties, of emerging ecosystems. It requires the ability to understand how and why species interact, as this will allow the development of mechanism-based predictive models, and as such to better characterize how ecological mechanisms act locally on the existence of interspecific interactions. Here we argue that the current conceptualization of species interaction networks is ill-suited for this task. Instead, we propose that future research must start to account for the intrinsic variability of species interactions, then scale up from here onto complex networks. This can be accomplished simply by recognizing that there exists intra-specific variability, in traits or properties related to the establishment of species interactions. By shifting the scale towards population-based processes, we show that this new approach will improve our predictive ability and mechanistic understanding of how species interact over large spatial or temporal scales.

10.1111/oik.01719

biorxiv

10.1101/000307

Drosophila embryogenesis scales uniformly across temperature and developmentally diverse species

Steven Gregory Kuntz;Michael B Eisen;

Steven Gregory Kuntz

University of California, Berkeley

2013-11-12

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2013/11/12/000307.source.xml

Temperature affects both the timing and outcome of animal development, but the detailed effects of temperature on the progress of early development have been poorly characterized. To determine the impact of temperature on the order and timing of events during Drosophila melanogaster embryogenesis, we used time-lapse imaging to track the progress of embryos from shortly after egg laying through hatching at seven precisely maintained temperatures between 17.5{degrees}C and 32.5{degrees}C. We employed a combination of automated and manual annotation to determine when 36 milestones occurred in each embryo. D. melanogaster embryogenesis takes 33 hours at 17.5{degrees}C, and accelerates with increasing temperature to a low of 16 hours at 27.5{degrees}C, above which embryogenesis slows slightly. Remarkably, while the total time of embryogenesis varies over two fold, the relative timing of events from cellularization through hatching is constant across temperatures. To further explore the relationship between temperature and embryogenesis, we expanded our analysis to cover ten additional Drosophila species of varying climatic origins. Six of these species, like D. melanogaster, are of tropical origin, and embryogenesis time at different temperatures was similar for them all. D. mojavensis, a sub-tropical fly, develops slower than the tropical species at lower temperatures, while D. virilis, a temperate fly, exhibits slower development at all temperatures. The alpine sister species D. persimilis and D. pseudoobscura develop as rapidly as tropical flies at cooler temperatures, but exhibit diminished acceleration above 22.5{degrees}C and have drastically slowed development by 30{degrees}C. Despite ranging from 13 hours for D. erecta at 30{degrees}C to 46 hours for D. virilis at 17.5{degrees}C, the relative timing of events from cellularization through hatching is constant across all of the species and temperatures examined here, suggesting the existence of a previously unrecognized timer controlling the progress of embryogenesis that has been tuned by natural selection in response to the thermal environment in which each species lives.\n\nAuthor SummaryTemperature profoundly impacts the rate of development of \"cold-blooded\" animals, which proceeds far faster when it is warm. There is, however, no universal relationship. Closely related species can develop at markedly different speeds at the same temperature, likely resulting from environmental adaptation. This creates a major challenge when comparing development among species, as it is unclear whether they should be compared at the same temperature or under different conditions to maintain the same developmental rate. Facing this challenge while working with flies (Drosophila species), we found there was little data to inform this decision. So, using time-lapse imaging, precise temperature-control, and computational and manual video-analysis, we tracked the complex process of embryogenesis in 11 species at seven different temperatures. There was over a three-fold difference in developmental rate between the fastest species at its fastest temperature and the slowest species at its slowest temperature. However, our finding that the timing of events within development all scaled uniformly across species and temperatures astonished us. This is good news for developmental biologists, since we can induce species to develop nearly identically by growing them at different temperatures. But it also means flies must possess some unknown clock-like molecular mechanism driving embryogenesis forward.

10.1371/journal.pgen.1004293

biorxiv

10.1101/000570

Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway

Helena Khaliullina;Mesut Bilgin;Julio L. Sampaio;Andrej Shevchenko;Suzanne Eaton;

Suzanne Eaton

Max-Planck-Institute of Molecular Cell Biology and Genetics

2013-11-18

New Results

cc_no

Developmental Biology

https://www.biorxiv.org/content/early/2013/11/18/000570.source.xml

Hedgehog proteins are lipid-modified secreted signaling molecules that regulate tissue development and homeostasis. Lipids contained in circulating lipoproteins repress the Hedgehog signaling pathway in the absence of Hedgehog ligand, but the identity of these lipids is unknown. Here, using biochemical fractionation and lipid mass spectrometry, we identify these inhibitory lipids as endocannabinoids. Endocannabinoids are present in lipoproteins of both flies and humans, and repress the pathway in both mammalian signaling assays and Drosophila wing imaginal discs. In Drosophila, endocannabinoids are required in vivo to keep the levels of Smoothened and full-length Cubitus interruptus (Ci155) low in the absence of Hedgehog. Furthermore, elevating their endogenous levels inhibits Hedgehog-dependent accumulation of Smoothened and Ci155. Interestingly, cannabis-derived phytocannabinoids are also potent pathway inhibitors in flies and mammals. These findings constitute a novel link between organismal metabolism and local Hedgehog signaling, and suggest previously unsuspected mechanisms for the broad physiological activities of cannabinoids.

biorxiv

10.1101/000653

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

David A Turner;Jamie Trott;Penelope Hayward;Pau Rué;Alfonso Martinez Arias;

Alfonso Martinez Arias

Department of Genetics. University of Cambridge. Cambridge CB2 3EH. UK.

2013-11-18

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2013/11/18/000653.source.xml

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst, retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analyzed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a \"race for fates\" at the level of single cells in which the neuroectodermal fate has an advantage.

10.1242/bio.20148409

biorxiv

10.1101/000653

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

David A Turner;Jamie Trott;Penelope Hayward;Pau Rué;Alfonso Martinez Arias;

Alfonso Martinez Arias

Department of Genetics. University of Cambridge. Cambridge CB2 3EH. UK.

2013-11-21

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2013/11/21/000653.source.xml

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst, retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analyzed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a \"race for fates\" at the level of single cells in which the neuroectodermal fate has an advantage.

10.1242/bio.20148409

biorxiv

10.1101/000653

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

David A Turner;Jamie Trott;Penelope Hayward;Pau Rué;Alfonso Martinez Arias;

Alfonso Martinez Arias

Department of Genetics. University of Cambridge. Cambridge CB2 3EH. UK.

2014-01-30

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2014/01/30/000653.source.xml

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst, retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analyzed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a \"race for fates\" at the level of single cells in which the neuroectodermal fate has an advantage.

10.1242/bio.20148409

biorxiv

10.1101/000653

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

David A Turner;Jamie Trott;Penelope Hayward;Pau Rué;Alfonso Martinez Arias;

Alfonso Martinez Arias

Department of Genetics. University of Cambridge. Cambridge CB2 3EH. UK.

2014-01-30

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2014/01/30/000653.source.xml

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst, retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analyzed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a \"race for fates\" at the level of single cells in which the neuroectodermal fate has an advantage.

10.1242/bio.20148409

biorxiv

10.1101/000653

An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

David A Turner;Jamie Trott;Penelope Hayward;Pau Rué;Alfonso Martinez Arias;

Alfonso Martinez Arias

Department of Genetics. University of Cambridge. Cambridge CB2 3EH. UK.

2014-06-30

New Results

cc_by

Developmental Biology

https://www.biorxiv.org/content/early/2014/06/30/000653.source.xml

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst, retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analyzed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a \"race for fates\" at the level of single cells in which the neuroectodermal fate has an advantage.

10.1242/bio.20148409

biorxiv

10.1101/001685

Stem cells in Nanomia bijuga (Siphonophora), a colonial animal with localized growth zones

Stefan Siebert;Freya E. Goetz;Samuel H. Church;Pathikrit Bhattacharyya;Felipe Zapata;Steven H.D. Haddock;Casey W. Dunn;

Stefan Siebert

Brown University

2014-01-06

New Results

cc_by_nc_nd

Developmental Biology

https://www.biorxiv.org/content/early/2014/01/06/001685.source.xml

BackgroundSiphonophores (Hydrozoa) have unparalleled colony-level complexity, precision of colony organization, and functional specialization between zooids (i.e., the units that make up colonies) Previous work has shown that, unlike other colonial animals, most growth in siphonophores is restricted to one or two well-defined growth zones that are the sites of both elongation and zooid budding. It remained unknown, however, how this unique colony growth and development is realized at the cellular level.\n\nResultsTo understand the colony-level growth and development of siphonophores at the cellular level, we characterize the distribution of proliferating cells and interstitial stem cells (i-cells) in the siphonophore Nanomia bijuga. Within the colony we find that i-cells are present at the tip of the horn, the structure within the growth zone that gives rise to new zooids. They persist in the youngest zooid buds, but as each zooid matures i-cells become progressively restricted to specific regions within the zooids until they are mostly absent from the oldest zooids. I-cell marker-gene expression remained in gametogenic regions. I-cells are not found in the stem between maturing zooids. Domains of high cell proliferation include regions where i-cells can be found, but also include some areas without i-cells such as the stem within the growth zones. Cell proliferation in regions devoid of marker gene expression indicates the presence of mitotically active epithelial cell lineages and, potentially, progenitor cell populations.\n\nConclusionsRestriction of stem cells to particular regions in the colony may play a major role in facilitating the precision of siphonophore growth, and also lead to a reduced developmental plasticity in other, typically older, parts of the colony. This helps explain why siphonophore colonies have such precise colony-level organization.

10.1186/s13227-015-0018-2

biorxiv

10.1101/001685

Stem cells in Nanomia bijuga (Siphonophora), a colonial animal with localized growth zones

Stefan Siebert;Freya E. Goetz;Samuel H. Church;Pathikrit Bhattacharyya;Felipe Zapata;Steven H.D. Haddock;Casey W. Dunn;

Stefan Siebert

Brown University

2015-03-16

New Results

cc_by_nc_nd

Developmental Biology

https://www.biorxiv.org/content/early/2015/03/16/001685.source.xml

BackgroundSiphonophores (Hydrozoa) have unparalleled colony-level complexity, precision of colony organization, and functional specialization between zooids (i.e., the units that make up colonies) Previous work has shown that, unlike other colonial animals, most growth in siphonophores is restricted to one or two well-defined growth zones that are the sites of both elongation and zooid budding. It remained unknown, however, how this unique colony growth and development is realized at the cellular level.\n\nResultsTo understand the colony-level growth and development of siphonophores at the cellular level, we characterize the distribution of proliferating cells and interstitial stem cells (i-cells) in the siphonophore Nanomia bijuga. Within the colony we find that i-cells are present at the tip of the horn, the structure within the growth zone that gives rise to new zooids. They persist in the youngest zooid buds, but as each zooid matures i-cells become progressively restricted to specific regions within the zooids until they are mostly absent from the oldest zooids. I-cell marker-gene expression remained in gametogenic regions. I-cells are not found in the stem between maturing zooids. Domains of high cell proliferation include regions where i-cells can be found, but also include some areas without i-cells such as the stem within the growth zones. Cell proliferation in regions devoid of marker gene expression indicates the presence of mitotically active epithelial cell lineages and, potentially, progenitor cell populations.\n\nConclusionsRestriction of stem cells to particular regions in the colony may play a major role in facilitating the precision of siphonophore growth, and also lead to a reduced developmental plasticity in other, typically older, parts of the colony. This helps explain why siphonophore colonies have such precise colony-level organization.

10.1186/s13227-015-0018-2

biorxiv

10.1101/000836

Journey to the Center of the Mitochondria Guided by the Tail Anchor of Protein Tyrosine Phosphatase 1B

Julia Fueller;Mikhail Egorov;Kirstin A. Walther;Ola Sabet;Jana Mallah;Markus Grabenbauer;Ali Kinkhabwala;

Ali Kinkhabwala

Max Planck Institute of Molecular Physiology

2013-11-22

New Results

cc_by

Cell Biology

https://www.biorxiv.org/content/early/2013/11/22/000836.source.xml

The canonical protein tyrosine phosphatase PTP1B has traditionally been considered to exclusively reside on the endoplasmic reticulum (ER). Using confocal microscopy, we show that endogenous PTP1B actually exhibits a higher local concentration at the mitochondria in all mammalian cell lines that we tested. Fluorescently labeled chimeras containing full-length PTP1B or only its 35 amino acid tail anchor localized identically, demonstrating the complete dependence of PTP1Bs subcellular partitioning on its tail anchor. Correlative light and electron microscopy using GFP-driven photo-oxidation of DAB revealed that PTP1Bs tail anchor localizes it to the mitochondrial interior and to mitochondrial-associated membrane (MAM) sites along the ER. Heterologous expression of the tail anchor of PTP1B in the yeast S. cerevisiae surprisingly led to its exclusive localization to the ER/vacuole with no presence at the mitochondria. Studies with various yeast mutants of conserved membrane insertion pathways revealed a role for the GET/TRC40 pathway in ER insertion, but also emphasized the likely dominant role of spontaneous insertion. Further studies of modified tail isoforms in both yeast and mammalian cells revealed a remarkable sensitivity of subcellular partitioning to slight changes in transmembrane domain (TMD) length, C-terminal charge, and hydropathy. For example, addition of a single positive charge to the tail anchor was sufficient to completely shift the tail anchor to the mitochondria in mammalian cells and to largely shift it there in yeast cells, and a point mutation that increased TMD hydropathy was sufficient to localize the tail anchor exclusively to the ER in mammalian cells. Striking differences in the subcellular partitioning of a given tail anchor isoform in mammalian versus yeast cells most likely point to fundamental differences in the lipid composition of specific organelles (e.g. affecting membrane charge or thickness) in higher versus lower eukaryotes. Fluorescence lifetime imaging microscopy (FLIM) detection of the Forster Resonance Energy Transfer (FRET)-based interaction of the catalytic domain of PTP1B with the epidermal growth factor receptor (EGFR/ErbB1) at the mitochondria revealed a strong interaction on the cytosolic face of the outer mitochondrial membrane (OMM), suggesting the presence of a significant pool of PTP1B there and a novel role for PTP1B in the regulation of mitochondrial ErbB1 activity. In summary, in addition to its well-established general localization along the ER, our results reveal that PTP1B specifically accumulates at MAM sites along the ER and localizes as well to the OMM and mitochondrial matrix. Further elucidation of PTP1Bs roles in these different locations (including the identification of its targets) will likely be critical for understanding its complex regulation of general cellular responses, cell proliferation, and diseased states.

biorxiv

10.1101/001602

p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition

Senthil K Radhakrishnan;Willem den Besten;Raymond J Deshaies;

Raymond J Deshaies

California Institute of Technology

2013-12-29

New Results

cc_no

Cell Biology

https://www.biorxiv.org/content/early/2013/12/29/001602.source.xml

Proteasome inhibition elicits an evolutionarily conserved response wherein proteasome subunit mRNAs are upregulated, resulting in recovery of proteasome activity. We previously demonstrated that the transcription factor Nrf1 mediates this homeostatic response in mammalian cells. We show here that Nrf1 is initially translocated into the lumen of the ER, but is rapidly and efficiently retrotranslocated to the cytosolic side of the membrane in a manner that depends on p97/VCP. Normally, retrotranslocated Nrf1 is degraded by the proteasome and active species do not accumulate. However, in cells with compromised proteasomes, retrotranslocated Nrf1 escapes degradation and is cleaved N-terminal to Leu-104 to yield a fragment that is no longer tethered to the ER-membrane. Importantly, this cleavage event is essential for Nrf1-dependent activation of proteasome gene expression upon proteasome inhibition. Our data uncover an unexpected role for p97 in activation of a transcription factor by relocalizing it from the ER lumen to the cytosol.

10.7554/eLife.01856.001

biorxiv

10.1101/001602

p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition

Senthil K Radhakrishnan;Willem den Besten;Raymond J Deshaies;

Raymond J Deshaies

California Institute of Technology

2013-12-30

New Results

cc_no

Cell Biology

https://www.biorxiv.org/content/early/2013/12/30/001602.source.xml

Proteasome inhibition elicits an evolutionarily conserved response wherein proteasome subunit mRNAs are upregulated, resulting in recovery of proteasome activity. We previously demonstrated that the transcription factor Nrf1 mediates this homeostatic response in mammalian cells. We show here that Nrf1 is initially translocated into the lumen of the ER, but is rapidly and efficiently retrotranslocated to the cytosolic side of the membrane in a manner that depends on p97/VCP. Normally, retrotranslocated Nrf1 is degraded by the proteasome and active species do not accumulate. However, in cells with compromised proteasomes, retrotranslocated Nrf1 escapes degradation and is cleaved N-terminal to Leu-104 to yield a fragment that is no longer tethered to the ER-membrane. Importantly, this cleavage event is essential for Nrf1-dependent activation of proteasome gene expression upon proteasome inhibition. Our data uncover an unexpected role for p97 in activation of a transcription factor by relocalizing it from the ER lumen to the cytosol.

10.7554/eLife.01856.001

biorxiv