Publications by authors named "Felix Breden"

60 Publications

Extreme Y chromosome polymorphism corresponds to five male reproductive morphs of a freshwater fish.

Nat Ecol Evol 2021 07 6;5(7):939-948. Epub 2021 May 6.

Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.

Loss of recombination between sex chromosomes often depletes Y chromosomes of functional content and genetic variation, which might limit their potential to generate adaptive diversity. Males of the freshwater fish Poecilia parae occur as one of five discrete morphs, all of which shoal together in natural populations where morph frequency has been stable for over 50 years. Each morph uses a different complex reproductive strategy and morphs differ dramatically in colour, body size and mating behaviour. Morph phenotype is passed perfectly from father to son, indicating there are five Y haplotypes segregating in the species, which encode the complex male morph characteristics. Here, we examine Y diversity in natural populations of P. parae. Using linked-read sequencing on multiple P. parae females and males of all five morphs, we find that the genetic architecture of the male morphs evolved on the Y chromosome after recombination suppression had occurred with the X. Comparing Y chromosomes between each of the morphs, we show that, although the Ys of the three minor morphs that differ in colour are highly similar, there are substantial amounts of unique genetic material and divergence between the Ys of the three major morphs that differ in reproductive strategy, body size and mating behaviour. Altogether, our results suggest that the Y chromosome is able to overcome the constraints of recombination loss to generate extreme diversity, resulting in five discrete Y chromosomes that control complex reproductive strategies.
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http://dx.doi.org/10.1038/s41559-021-01452-wDOI Listing
July 2021

The ADC API: A Web API for the Programmatic Query of the AIRR Data Commons.

Front Big Data 2020 17;3:22. Epub 2020 Jun 17.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States.

The Adaptive Immune Receptor Repertoire (AIRR) Community is a research-driven group that is establishing a clear set of community-accepted data and metadata standards; standards-based reference implementation tools; and policies and practices for infrastructure to support the deposit, curation, storage, and use of high-throughput sequencing data from B-cell and T-cell receptor repertoires (AIRR-seq data). The AIRR Data Commons is a distributed system of data repositories that utilizes a common data model, a common query language, and common interoperability formats for storage, query, and downloading of AIRR-seq data. Here is described the principal technical standards for the AIRR Data Commons consisting of the AIRR Data Model for repertoires and rearrangements, the AIRR Data Commons (ADC) API for programmatic query of data repositories, a reference implementation for ADC API services, and tools for querying and validating data repositories that support the ADC API. AIRR-seq data repositories can become part of the AIRR Data Commons by implementing the data model and API. The AIRR Data Commons allows AIRR-seq data to be reused for novel analyses and empowers researchers to discover new biological insights about the adaptive immune system.
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http://dx.doi.org/10.3389/fdata.2020.00022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931935PMC
June 2020

The adaptive immune receptor repertoire community as a model for FAIR stewardship of big immunology data.

Curr Opin Syst Biol 2020 Dec 10;24:71-77. Epub 2020 Oct 10.

Department of Biological Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.

Systems biology involves network-oriented, computational approaches to modeling biological systems through analysis of big biological data. To contribute maximally to scientific progress, big biological data should be FAIR: findable, accessible, interoperable, and reusable. Here, we describe high-throughput sequencing data that characterize the vast diversity of B- and T-cell clones comprising the adaptive immune receptor repertoire (AIRR-seq data) and its contribution to our understanding of COVID-19 (coronavirus disease 19). We describe the accomplishments of the AIRR community, a grass-roots network of interdisciplinary laboratory scientists, bioinformaticians, and policy wonks, in creating and publishing standards, software and repositories for AIRR-seq data based on the FAIR principles.
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http://dx.doi.org/10.1016/j.coisb.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547575PMC
December 2020

Divergence and Remarkable Diversity of the Y Chromosome in Guppies.

Mol Biol Evol 2021 01;38(2):619-633

Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.

The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared with their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female preference for rare Y-linked color variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence.
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http://dx.doi.org/10.1093/molbev/msaa257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826173PMC
January 2021

Extreme heterogeneity in sex chromosome differentiation and dosage compensation in livebearers.

Proc Natl Acad Sci U S A 2019 09 4;116(38):19031-19036. Epub 2019 Sep 4.

Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.

Once recombination is halted between the X and Y chromosomes, sex chromosomes begin to differentiate and transition to heteromorphism. While there is a remarkable variation across clades in the degree of sex chromosome divergence, far less is known about the variation in sex chromosome differentiation within clades. Here, we combined whole-genome and transcriptome sequencing data to characterize the structure and conservation of sex chromosome systems across Poeciliidae, the livebearing clade that includes guppies. We found that the XY system is much older than previously thought, being shared not only with its sister species, , but also with , which diverged roughly 20 million years ago. Despite the shared ancestry, we uncovered an extreme heterogeneity across these species in the proportion of the sex chromosome with suppressed recombination, and the degree of Y chromosome decay. The sex chromosomes in and are largely homomorphic, with recombination in the former persisting over a substantial fraction. However, the sex chromosomes in are completely nonrecombining and strikingly heteromorphic. Remarkably, the profound degradation of the ancestral Y chromosome in is counterbalanced by the evolution of functional chromosome-wide dosage compensation in this species, which has not been previously observed in teleost fish. Our results offer important insight into the initial stages of sex chromosome evolution and dosage compensation.
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http://dx.doi.org/10.1073/pnas.1905298116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754558PMC
September 2019

On the power to detect rare recombination events.

Proc Natl Acad Sci U S A 2019 06 18;116(26):12607-12608. Epub 2019 Jun 18.

Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.

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http://dx.doi.org/10.1073/pnas.1905555116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601268PMC
June 2019

Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming.

Front Immunol 2019 18;10:435. Epub 2019 Mar 18.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT, the international ImMunoGeneTics information system (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.
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http://dx.doi.org/10.3389/fimmu.2019.00435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431624PMC
September 2020

Reviewing guppy color vision: integrating the molecular and physiological variation in visual tuning of a classic system for sensory drive.

Curr Zool 2018 Aug 9;64(4):535-545. Epub 2018 Jun 9.

Department of Biology, University of Maryland, College Park, College Park, MD, USA.

Sensory drive predicts coevolution of mate choice signals with the sensory systems detecting those signals. Guppies are a classic model for sensory drive as mate preferences based on coloration differ across individuals and populations. A large body of work has identified variation in color vision, yet we lack a direct tie between how such variation in color vision influences variation in color preference. Here we bring together studies that have investigated guppy vision over the past 40 years to: (1) highlight our current understanding of where variation occurs in the guppy color vision pathway and (2) suggest future avenues of research into sources of visual system variation that could influence guppy color preference. This will allow researchers to design careful studies that couple measures of color preference with measures of visual system variation from the same individual or population. Such studies will finally provide important answers as to what sets the direction and speed of mate preference evolution via sensory drive.
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http://dx.doi.org/10.1093/cz/zoy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084590PMC
August 2018

iReceptor: A platform for querying and analyzing antibody/B-cell and T-cell receptor repertoire data across federated repositories.

Immunol Rev 2018 07;284(1):24-41

The IRMACS Centre, Simon Fraser University, Burnaby, BC, Canada.

Next-generation sequencing allows the characterization of the adaptive immune receptor repertoire (AIRR) in exquisite detail. These large-scale AIRR-seq data sets have rapidly become critical to vaccine development, understanding the immune response in autoimmune and infectious disease, and monitoring novel therapeutics against cancer. However, at present there is no easy way to compare these AIRR-seq data sets across studies and institutions. The ability to combine and compare information for different disease conditions will greatly enhance the value of AIRR-seq data for improving biomedical research and patient care. The iReceptor Data Integration Platform (gateway.ireceptor.org) provides one implementation of the AIRR Data Commons envisioned by the AIRR Community (airr-community.org), an initiative that is developing protocols to facilitate sharing and comparing AIRR-seq data. The iReceptor Scientific Gateway links distributed (federated) AIRR-seq repositories, allowing sequence searches or metadata queries across multiple studies at multiple institutions, returning sets of sequences fulfilling specific criteria. We present a review of the development of iReceptor, and how it fits in with the general trend toward sharing genomic and health data, and the development of standards for describing and reporting AIRR-seq data. Researchers interested in integrating their repositories of AIRR-seq data into the iReceptor Platform are invited to contact [email protected]
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http://dx.doi.org/10.1111/imr.12666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344122PMC
July 2018

Reproducibility and Reuse of Adaptive Immune Receptor Repertoire Data.

Front Immunol 2017 1;8:1418. Epub 2017 Nov 1.

Department of Microbiology, Boston University School of Medicine, Boston, MA, United States.

High-throughput sequencing (HTS) of immunoglobulin (B-cell receptor, antibody) and T-cell receptor repertoires has increased dramatically since the technique was introduced in 2009 (1-3). This experimental approach explores the maturation of the adaptive immune system and its response to antigens, pathogens, and disease conditions in exquisite detail. It holds significant promise for diagnostic and therapy-guiding applications. New technology often spreads rapidly, sometimes more rapidly than the understanding of how to make the products of that technology reliable, reproducible, or usable by others. As complex technologies have developed, scientific communities have come together to adopt common standards, protocols, and policies for generating and sharing data sets, such as the MIAME protocols developed for microarray experiments. The Adaptive Immune Receptor Repertoire (AIRR) Community formed in 2015 to address similar issues for HTS data of immune repertoires. The purpose of this perspective is to provide an overview of the AIRR Community's founding principles and present the progress that the AIRR Community has made in developing standards of practice and data sharing protocols. Finally, and most important, we invite all interested parties to join this effort to facilitate sharing and use of these powerful data sets ([email protected]).
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http://dx.doi.org/10.3389/fimmu.2017.01418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671925PMC
November 2017

Genomic Environment Impacts Color Vision Evolution in a Family with Visually Based Sexual Selection.

Genome Biol Evol 2017 Nov;9(11):3100-3107

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.

Many models of evolution by sexual selection predict a coevolution of sensory systems and mate preferences, but the genomic architecture (number and arrangement of contributing loci) underlying these characters could constrain this coevolution. Here, we examine how the genomic organization and evolution of the opsin genes (responsible for tuning color vision) can influence the evolutionary trajectory of sexually selected traits across 15 species in the family Poeciliidae, which includes classic systems for studies of color-mediated sexual selection such as guppies, swordtails, and mollies. Although male coloration patterns and the importance of this coloration in female mate choice vary widely within and among genera, sequencing revealed low variability at amino acid sites that tune Long Wavelength-Sensitive (LWS) opsins in this speciose family. Although most opsin genes in these species appear to have evolved along traditional mutation-selection dynamics, we identified high rates of gene conversion between two of the LWS loci (LWS-1 and LWS-3), likely due to the inverted tandem repeat nature of these genes. Yet members of the subgenus Lebistes appear to resist LWS gene conversion. The LWS opsins are responsible for detecting and discriminating red and orange coloration-a key sexually selected trait in members of the subgenus Lebistes. Taken together these results suggest selection is acting against the homogenizing effects of gene conversion to maintain LWS-1/LWS-3 differences within this subgenus.
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http://dx.doi.org/10.1093/gbe/evx228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714168PMC
November 2017

Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation.

Nat Commun 2017 01 31;8:14251. Epub 2017 Jan 31.

Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.

Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution.
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http://dx.doi.org/10.1038/ncomms14251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290318PMC
January 2017

Using High-Throughput Sequencing to Characterize the Development of the Antibody Repertoire During Infections: A Case Study of HIV-1.

Adv Exp Med Biol 2017 ;1053:245-263

Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.

High throughput sequencing (HTS) approaches have only recently been applied to describing the antibody/B-cell repertoire in fine detail, but these data sets have already become critical to the design of vaccines and therapeutics, and monitoring of cancer immunotherapy. As a case study, we describe the potential and present limitations of HTS studies of the Ab repertoire during infection with HIV-1. Most of the present studies restrict their analyses to lineages of specific bnAbs. We discuss future initiatives to expand this type of analysis to more complete repertoires and to improve comparing and sharing of these Ab repertoire data across studies and institutions.
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http://dx.doi.org/10.1007/978-3-319-72077-7_12DOI Listing
August 2018

VDJML: a file format with tools for capturing the results of inferring immune receptor rearrangements.

BMC Bioinformatics 2016 Oct 6;17(Suppl 13):333. Epub 2016 Oct 6.

Department of Clinical Sciences, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9066, USA.

Background: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens. Characterization of immune repertoires is critical in both basic research and clinical contexts. Recent technological advances in repertoire profiling via high-throughput sequencing have resulted in an explosion of research activity in the field. This has been accompanied by a proliferation of software tools for analysis of repertoire sequencing data. Despite the widespread use of immune repertoire profiling and analysis software, there is currently no standardized format for output files from V(D)J analysis. Researchers utilize software such as IgBLAST and IMGT/High V-QUEST to perform V(D)J analysis and infer the structure of germline rearrangements. However, each of these software tools produces results in a different file format, and can annotate the same result using different labels. These differences make it challenging for users to perform additional downstream analyses.

Results: To help address this problem, we propose a standardized file format for representing V(D)J analysis results. The proposed format, VDJML, provides a common standardized format for different V(D)J analysis applications to facilitate downstream processing of the results in an application-agnostic manner. The VDJML file format specification is accompanied by a support library, written in C++ and Python, for reading and writing the VDJML file format.

Conclusions: The VDJML suite will allow users to streamline their V(D)J analysis and facilitate the sharing of scientific knowledge within the community. The VDJML suite and documentation are available from https://vdjserver.org/vdjml/ . We welcome participation from the community in developing the file format standard, as well as code contributions.
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http://dx.doi.org/10.1186/s12859-016-1214-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073965PMC
October 2016

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity.

Sci Rep 2016 Feb 16;6:20842. Epub 2016 Feb 16.

Department of Cancer Immunology &AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.

IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of "universal" influenza vaccine.
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http://dx.doi.org/10.1038/srep20842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754645PMC
February 2016

Poecilia picta, a Close Relative to the Guppy, Exhibits Red Male Coloration Polymorphism: A System for Phylogenetic Comparisons.

PLoS One 2015 3;10(11):e0142089. Epub 2015 Nov 3.

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.

Studies on the evolution of female preference and male color polymorphism frequently focus on single species since traits and preferences are thought to co-evolve. The guppy, Poecilia reticulata, has long been a premier model for such studies because female preferences and orange coloration are well known to covary, especially in upstream/downstream pairs of populations. However, focused single species studies lack the explanatory power of the comparative method, which requires detailed knowledge of multiple species with known evolutionary relationships. Here we describe a red color polymorphism in Poecilia picta, a close relative to guppies. We show that this polymorphism is restricted to males and is maintained in natural populations of mainland South America. Using tests of female preference we show female P. picta are not more attracted to red males, despite preferences for red/orange in closely related species, such as P. reticulata and P. parae. Male color patterns in these closely related species are different from P. picta in that they occur in discrete patches and are frequently Y chromosome-linked. P. reticulata have an almost infinite number of male patterns, while P. parae males occur in discrete morphs. We show the red male polymorphism in P. picta extends continuously throughout the body and is not a Y-linked trait despite the theoretical prediction that sexually-selected characters should often be linked to the heterogametic sex chromosome. The presence/absence of red male coloration of P. picta described here makes this an ideal system for phylogenetic comparisons that could reveal the evolutionary forces maintaining mate choice and color polymorphisms in this speciose group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142089PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631359PMC
June 2016

Color vision varies more among populations than among species of live-bearing fish from South America.

BMC Evol Biol 2015 Oct 16;15:225. Epub 2015 Oct 16.

Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, V5A 1S6, BC, Canada.

Background: Sensory Bias models for the evolution of mate preference place a great emphasis on the role of sensory system variation in mate preferences. However, the extent to which sensory systems vary across- versus within-species remains largely unknown. Here we assessed whether color vision varies in natural locations where guppies (Poecilia reticulata) and their two closest relatives, Poecilia parae and Poecilia picta, occur in extreme sympatry and school together. All three species base mate preferences on male coloration but differ in the colors preferred.

Results: Measuring opsin gene expression, we found that within sympatric locations these species have similar color vision and that color vision differed more across populations of conspecifics. In addition, all three species differ across populations in the frequency of the same opsin coding polymorphism that influences visual tuning.

Conclusions: Together, this shows sensory systems vary considerably across populations and supports the possibility that sensory system variation is involved in population divergence of mate preference.
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http://dx.doi.org/10.1186/s12862-015-0501-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609137PMC
October 2015

Developmental plasticity in vision and behavior may help guppies overcome increased turbidity.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2015 Dec 1;201(12):1125-35. Epub 2015 Oct 1.

Department of Environmental Science and Policy, University of California-Davis, One Shields Ave., Davis, CA, 95616, USA.

Increasing turbidity in streams and rivers near human activity is cause for environmental concern, as the ability of aquatic organisms to use visual information declines. To investigate how some organisms might be able to developmentally compensate for increasing turbidity, we reared guppies (Poecilia reticulata) in either clear or turbid water. We assessed the effects of developmental treatments on adult behavior and aspects of the visual system by testing fish from both developmental treatments in turbid and clear water. We found a strong interactive effect of rearing and assay conditions: fish reared in clear water tended to decrease activity in turbid water, whereas fish reared in turbid water tended to increase activity in turbid water. Guppies from all treatments decreased activity when exposed to a predator. To measure plasticity in the visual system, we quantified treatment differences in opsin gene expression of individuals. We detected a shift from mid-wave-sensitive opsins to long wave-sensitive opsins for guppies reared in turbid water. Since long-wavelength sensitivity is important in motion detection, this shift likely allows guppies to salvage motion-detecting abilities when visual information is obscured in turbid water. Our results demonstrate the importance of developmental plasticity in responses of organisms to rapidly changing environments.
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http://dx.doi.org/10.1007/s00359-015-1041-4DOI Listing
December 2015

Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences.

Philos Trans R Soc Lond B Biol Sci 2015 Jul;370(1673)

Department of Psychology, Arizona State University, Tempe, AZ, USA Center for Evolution and Cancer, University of California San Francisco, San Francisco, CA, USA Wissenschaftskolleg zu Berlin, Institute for Advanced Study, 14193 Berlin, Germany.

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction.
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http://dx.doi.org/10.1098/rstb.2014.0220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581025PMC
July 2015

Beauty in the eyes of the beholders: colour vision is tuned to mate preference in the Trinidadian guppy (Poecilia reticulata).

Mol Ecol 2015 Feb;24(3):596-609

Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.

A broad range of animals use visual signals to assess potential mates, and the theory of sensory exploitation suggests variation in visual systems drives mate preference variation due to sensory bias. Trinidadian guppies (Poecilia reticulata), a classic system for studies of the evolution of female mate choice, provide a unique opportunity to test this theory by looking for covariation in visual tuning, light environment and mate preferences. Female preference co-evolves with male coloration, such that guppy females from 'low-predation' environments have stronger preferences for males with more orange/red coloration than do females from 'high-predation' environments. Here, we show that colour vision also varies across populations, with 'low'-predation guppies investing more of their colour vision to detect red/orange coloration. In independently colonized watersheds, guppies expressed higher levels of both LWS-1 and LWS-3 (the most abundant LWS opsins) in 'low-predation' populations than 'high-predation' populations at a time that corresponds to differences in cone cell abundance. We also observed that the frequency of a coding polymorphism differed between high- and low-predation populations. Together, this shows that the variation underlying preference could be explained by simple changes in expression and coding of opsins, providing important candidate genes to investigate the genetic basis of female preference variation in this model system.
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http://dx.doi.org/10.1111/mec.13058DOI Listing
February 2015

Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity.

Genes Immun 2015 Jan-Feb;16(1):24-34. Epub 2014 Oct 23.

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.

Germline variation at immunoglobulin (IG) loci is critical for pathogen-mediated immunity, but establishing complete haplotype sequences in these regions has been problematic because of complex sequence architecture and diploid source DNA. We sequenced BAC clones from the effectively haploid human hydatidiform mole cell line, CHM1htert, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype generated here is 1.25 Mb of contiguous sequence, including four novel IGLV alleles, one novel IGLC allele, and an 11.9-kb insertion. The CH17 IGK haplotype consists of two 644 kb proximal and 466 kb distal contigs separated by a large gap of unknown size; these assemblies added 49 kb of unique sequence extending into this gap. Our analysis also resulted in the characterization of seven novel IGKV alleles and a 16.7-kb region exhibiting signatures of interlocus sequence exchange between distal and proximal IGKV gene clusters. Genetic diversity in IGK/IGL was compared with that of the IG heavy chain (IGH) locus within the same haploid genome, revealing threefold (IGK) and sixfold (IGL) higher diversity in the IGH locus, potentially associated with increased levels of segmental duplication and the telomeric location of IGH.
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http://dx.doi.org/10.1038/gene.2014.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304971PMC
August 2015

Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

MAbs 2014 May-Jun;6(3):577-618. Epub 2014 Mar 3.

University of Maryland; Baltimore, MD USA.

The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.
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http://dx.doi.org/10.4161/mabs.28421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011904PMC
May 2015

Population structure of guppies in north-eastern Venezuela, the area of putative incipient speciation.

BMC Evol Biol 2014 Feb 17;14(1):28. Epub 2014 Feb 17.

Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, Krakow 30-387, Poland.

Background: Geographic barriers to gene flow and divergence among populations in sexual traits are two important causes of genetic isolation which may lead to speciation. Genetic isolation may be facilitated if these two mechanisms act synergistically. The guppy from the Cumaná region (within the Cariaco drainage) of eastern Venezuela has been previously described as a case of incipient speciation driven by sexual selection, significantly differentiated in sexual colouration and body shape from the common guppy, Poecilia reticulata. The latter occurs widely in northern Venezuela, including the south-eastern side of Cordillera de la Costa, where it inhabits streams belonging to the San Juan drainage. Here, we present molecular and morphological analyses of differentiation among guppy populations in the Cariaco and San Juan drainages. Our analyses are based on a 953 bp long mtDNA fragment, a set of 15 microsatellites (519 fish from 20 populations), and four phenotypic traits.

Results: Both microsatellite and mtDNA data showed that guppies inhabiting the two drainages are characterised by a significant genetic differentiation, but a higher proportion of the genetic variance was distributed among populations within regions. Most guppies in the Cariaco drainage had mtDNA from a distinct lineage, but we also found evidence for widespread introgression of mtDNA from the San Juan drainage into the Cariaco drainage. Phenotypically, populations in the two regions differed significantly only in the number of black crescents. Phenotypic clustering did not support existence of two distinct groupings, but indicated a degree of distinctiveness of Central Cumaná (CC) population. However, CC population showed little differentiation at the neutral markers from the proximate populations within the Cariaco drainage.

Conclusions: Our findings are consistent with only partial genetic isolation between the two geographic regions and indicate that the geographic barrier of Cordillera de la Costa has not played an important role in strengthening the incomplete pre-zygotic reproductive barrier between Cumaná and common guppy. Significant phenotypic differentiation between genetically similar (in terms of neutral variation) populations suggests that mate choice can maintain divergence at sexually selected traits despite gene flow. However, neither genetic nor phenotypic clustering supported delineation of two species within the region.
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http://dx.doi.org/10.1186/1471-2148-14-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942120PMC
February 2014

Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation.

Am J Hum Genet 2013 Apr 28;92(4):530-46. Epub 2013 Mar 28.

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.

The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody heavy-chain biosynthesis, which is vital to the adaptive immune response. Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the locus have impeded attempts to reconcile its genomic organization based on traditional B-lymphocyte derived genetic material. As a result, sequence descriptions of germline variation within IGHV are lacking, haplotype inference using traditional linkage disequilibrium methods has been difficult, and the human genome reference assembly is missing several expressed IGHV genes. By using a hydatidiform mole BAC clone resource, we present the most complete haplotype of IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing an alternate assembly of ∼1 Mbp of high-quality finished sequence. From this we add 101 kbp of previously uncharacterized sequence, including functional IGHV genes, and characterize four large germline copy-number variants (CNVs). In addition to this germline reference, we identify and characterize eight CNV-containing haplotypes from a panel of nine diploid genomes of diverse ethnic origin, discovering previously unmapped IGHV genes and an additional 121 kbp of insertion sequence. We genotype four of these CNVs by using PCR in 425 individuals from nine human populations. We find that all four are highly polymorphic and show considerable evidence of stratification (Fst = 0.3-0.5), with the greatest differences observed between African and Asian populations. These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial arrays in most of the populations tested.
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http://dx.doi.org/10.1016/j.ajhg.2013.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617388PMC
April 2013

Hybridization leads to sensory repertoire expansion in a gynogenetic fish, the Amazon molly (poecilia formosa): a test of the hybrid-sensory expansion hypothesis.

Evolution 2013 Jan 7;67(1):120-30. Epub 2012 Sep 7.

Department of Biological Sciences, Simon Fraser University, Burnaby BC, V5A 1S6, Canada.

Expansions in sensory systems usually require processes such as gene duplication and divergence, and thus evolve slowly. We evaluate a novel mechanism leading to rapid sensory repertoire expansion: hybrid-sensory expansion (HSE). HSE occurs when two species with differently tuned sensory systems form a hybrid, bringing together alleles from each of the parental species. In one generation, a sensory repertoire is created that is the sum of the variance between parental species. The Amazon molly presents a unique opportunity to test the HSE hypothesis in a "frozen" hybrid. We compared opsin sequences of the Amazon molly, Poecilia formosa, to those of the parental species. Both parental species are homozygous at the RH2-1 locus and each of the four long wavelength sensitive loci, while P. formosa possess two different alleles at these loci; one matching each parental allele. Gene expression analysis showed P. formosa use the expanded opsin repertoire that was the result of HSE. Additionally, behavioral tests revealed P. formosa respond to colored stimuli in a manner similar or intermediate to the parental species P. mexicana and P. latipinna. Together these results strongly support the HSE hypothesis. Hybrid-sensory repertoire expansion is likely important in other hybrid species and in other sensory systems.
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http://dx.doi.org/10.1111/j.1558-5646.2012.01779.xDOI Listing
January 2013

Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs.

Sci Rep 2012 25;2:770. Epub 2012 Oct 25.

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.

Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.
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http://dx.doi.org/10.1038/srep00770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480808PMC
March 2013
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