Felix Breden

Simon Fraser University · Department of Biological Sciences

Reproductive isolation drives the formation of new species, and many genes contribute to this through Dobzhansky-Muller incompatibilities (DMIs). These incompatibilities occur when gene divergence affects loci encoding interacting products such as receptors and their ligands. We suggest here that the nature of vertebrate immunoglobulin (IG) genes m...

Differences in allele frequencies at autosomal genes between males and females in a population can result from two scenarios. First, unresolved sexual conflict over survival can produce allelic differentiation between the sexes. However, given the substantial mortality costs required to produce allelic differences between males and females at each...

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...

Immunogenomics studies have been largely limited to individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations. Inclusion of a greater diversity of individuals in immunogenomics studies will substantially enhance our understanding of human immunology.

Sexual conflict over survival produces two distinct population genetic signatures. Fluctuating selection in males and females produces balancing selection. Additionally, at conception, allele frequencies are the same in males and females. However, loci with alleles that benefit the survival of one sex at some survival cost to the other should diver...

With the recent advent of high-throughput sequencing technologies, and the associated new discoveries and developments, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. The majority of immunogenomics studies have been primarily conducted in cohorts of European ancestry, rest...

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...

Sex chromosomes form once recombination is halted between the X and Y chromosomes. This loss of recombination quickly depletes Y chromosomes of functional content and genetic variation, which is thought to severely limit their potential to generate adaptive diversity. We examined Y diversity in Poecilia parae , where males occur as one of five disc...

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...

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 fr...

Once recombination is halted between the X and Y chromosomes, sex chromosomes begin to differentiate and transition to hetero-morphism. 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...

Once recombination is halted between the X and Y chromosome, 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 variation in sex chromosome differentiation within clades. Here, we combined whole genome and tr...

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...

Sensory drive predicts co-evolution 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 variati...

Many models of evolution by sexual selection predict a co-evolution of sensory systems and mate preferences, but the genomic architecture (number and arrangement of contributing loci) underlying these characters could constrain this co-evolution. Here we examine how the genomic organization and evolution of the opsin genes (responsible for tuning c...

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 deta...

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...

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...

Despite the widespread use of immune repertoire profiling, there is currently no standardized format for output files from VDJ analysis. Researchers utilize software such as IgBlast and IMGT/High V-Quest to perform VDJ analysis and infer germline rearrangements. Each of these software tools produces results in a different file format, and can ident...

Scientific Reports 6 : Article number: 20842; 10.1038/srep20842 published online: 16 February 2016 ; updated: 29 April 2016 . In this Article, the Figure labels were omitted from Figure 5b.

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,...

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...

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/downstrea...

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 r...

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 de...

The cervical mucosa of women who are highly exposed to HIV-1, yet remain persistently seronegative (HEPS), presents a unique opportunity to study the dynamics of an immune compartment potentially capable of preventing HIV-1 infection. Herein, we provide a detailed characterization of the immunoglobulin repertoire of cervical and systemic B cells fr...

Germline variation at immunoglobulin gene (IG) loci is critical for pathogen-mediated immunity, but establishing complete reference sequences in these regions is problematic because of segmental duplications and somatically rearranged source DNA. We sequenced BAC clones from the essentially haploid hydatidiform mole, CHM1, across the light chain IG...

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 rec...

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...

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...

Recent associations between age-related differentially methylated sites and bivalently marked chromatin domains have implicated a role for these genomic regions in aging and age-related diseases. However, the overlap between such epigenetic modifications has so far only been identified with respect to age-associated hyper-methylated sites in blood....

Guppies are one of the best known examples of sexual selection in that females prefer to mate with more colorful males. This raises questions of how do guppies see color and why is color so important to them. Color vision is mediated by transmembrane proteins in the retina called opsins. The peak spectral sensitivity of an opsin is a function of it...

Vertebrate opsin genes often occur in sets of tandem duplicates, and their expression varies developmentally and in response to environmental cues. We previously identified two highly conserved regions upstream of the long-wave sensitive opsin (LWS) gene cluster in teleosts. This region has since been shown in zebrafish to drive expression of LWS g...

Expressed MAbs analyzed for CDR-H3 length, somatic mutations, and gene usage. (XLS)

Database of antigen-specific expressed human MAbs. (XLS)

VH gene family usage in anti-protein and non anti-protein MAbs for 3 disease conditions. See Table 3 for sample sizes; there is only 1 ChI Mab that is not anti-protein. MAbs utilizing VH1 family were separated into those using VH1-69 and others. (TIF)

Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the V...

The cervical mucosa of women who are highly exposed to HIV-1, yet remain persistently seronegative (HEPS), presents a unique opportunity to study the dynamics of an immune compartment potentially capable of preventing HIV-1 infection. Herein, we provide a detailed characterization of the immunoglobulin repertoire of cervical and systemic B cells fr...

Female preference for male orange coloration in the genus Poecilia suggests a role for duplicated long wavelength-sensitive (LWS) opsin genes in facilitating behaviors related to mate choice in these species. Previous work has shown that LWS gene duplication in this genus has resulted in expansion of long wavelength visual capacity as determined by...

Understanding the genetic basis of heritable spinal curvature would benefit medicine and aquaculture. Heritable spinal curvature among otherwise healthy children (i.e. Idiopathic Scoliosis and Scheuermann kyphosis) accounts for more than 80% of all spinal curvatures and imposes a substantial healthcare cost through bracing, hospitalizations, surger...

Polymorphic markers used for mapping. The supplemental file provides the markers that were polymorphic in curveback mapping crosses. All marker numbers and genetic locations are from the guppy linkage map (Tripathi, et al., 2009). Markers in bold were genotyped by either direct sequencing or by RFLP of PCR products. File is in Excel 97-2004 format.

Background Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the ev...

Here we compare the body shape of juvenile (age-0) sockeye salmon Oncorhynchus nerka that rear in lakes (lake type) with that of those that rear in rivers (riverine) and relate rearing habitat to morphology and ecology. The two habitats present different swimming challenges with respect to water flow, foraging strategy, habitat complexity, and pred...

The restricted use of immunoglobulin heavy chain variable (IGHV) family 4 gene segments by clonally expanded B cells in brain lesions and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients is well documented. Specifically, the overrepresentation of gene IGHV4-39 has been highlighted in multiple studies. To investigate the role of IGHV4-3...

* NOTE: This is a 'working draft' sequence. It currently * consists of 2 contigs. Gaps between the contigs * are represented as runs of N. The order of the pieces * is believed to be correct as given, however the sizes * of the gaps between them are based on estimates that have * provided by the submitter. * This sequence will be replaced * by the...

* NOTE: This is a 'working draft' sequence. It currently * consists of 4 contigs. Gaps between the contigs * are represented as runs of N. The order of the pieces * is believed to be correct as given, however the sizes * of the gaps between them are based on estimates that have * provided by the submitter. * This sequence will be replaced * by the...

The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature that develops during growth. Prior work has revealed several important developmental similarities to the human idiopathic scoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that are associated with sp...

LWS and SWS2 Maximum Parsimony phylogenies. MP trees for LWS (left) and SWS2 (right) genes, constructed from sequences and alignments used for NJ trees in Figs. 3 and 4. Gene sequences for Xenopus tropicalis SWS2 and LWS genes were used as outgroups. Within the tree, values from 1000 bootstrap reiterations are labelled at the nodes, and species and...

Alignment of Region I in Xenopus tropicalis and Anolis carolinensis. Region I: 90-94 bp of conserved sequence. Black brackets indicate regions with 100 percent shared sequence identity across the species shown. Two putative hormone response element (HRE) half-site arrangements are boxed in black, and black arrows indicate sequence direction of HRE...

PCR primers, and sequences used for Multipipmaker analysis. Top Left: A list of tools and databases utilized by the GRASP gene annotation pipeline. Top Right: PCR primers used for LWS opsin-positive X. helleri BAC clones, and for PCR screening of X. helleri adult female and male whole eye cDNA. PCR primers from other studies are referenced in "Refe...

Long wave-sensitive (LWS) opsin genes have undergone multiple lineage-specific duplication events throughout the evolution of teleost fishes. LWS repertoire expansions in live-bearing fishes (family Poeciliidae) have equipped multiple species in this family with up to four LWS genes. Given that color vision, especially attraction to orange male col...

Adaptation of guppies (Poecilia reticulata) to contrasting upland and lowland habitats has been extensively studied with respect to behaviour, morphology and life history traits. Yet population history has not been studied at the whole-genome level. Although single nucleotide polymorphisms (SNPs) are the most abundant form of variation in many geno...

A comparative allometric study of body lengths in an animal model for human idiopathic-type scoliosis. To compare body length variation among adult curved and noncurved curveback female guppies. Tallness and/or abnormal anthropometric parameters have been correlated to idiopathic-type scoliosis (IS) in numerous studies. Heritable curvature in curve...

Wild et al. argue that the evolution of reduced virulence can be understood from the perspective of inclusive fitness, obviating the need to evoke group selection as a contributing causal factor. Although they acknowledge the mathematical equivalence of the inclusive fitness and multilevel selection approaches, they conclude that reduced virulence...

Human familial/idiopathic-type scoliosis (IS) is a complex genetic disorder for which the cause is unknown. The curve phenotype characteristically demonstrates pronounced morphological and developmental variability that is likely a consequence of biomechanical, environmental, and genetic differences between individuals. In addition, risk factors th...

Exon alignment of LWS genes used in phylogenetic analysis. Common names are listed and acquisition numbers can be found in the methods section.

List of LWS primer names and sequences used for PCR, RT-PCR and qPCR. Primer names and numbers correspond to reaction conditions shown in Additional file 2. Primer numbers corresponds to amplicons shown in Additional file 3. Sequences are given in the 5'to 3' orientation. Primers were synthesized by Operon® Biotechnologies, suspended in sterile buf...

Primer and sequence maps for LWS opsin loci in Poeciliidae. Large colored boxes and horizontal bars represent exons and introns, respectively. Black and solid horizontal lines represent genomic sequences amplified using various PCR primer combinations (see legend; see Additional files 1 and 2). Dotted horizontal lines represent mRNA transcripts acq...

Sequence data and PCR conditions for specific primer combinations used for all six species of Poeciliidae. Primer names are given with corresponding primer number from Additional file 1. Amplicons are shown in Additional file 3 along with corresponding n value. 0.5 U iProof™ DNA polymerase (BioRad®) was used for each reaction with 5× iProof™ HF Buf...

Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of...

This study investigated the morphology, pathogenesis, and inheritance of idiopathic-like spinal curvature in the guppy syndrome, curveback. To determine whether curveback could be applied as a model for the primary factors that contribute to heritable spinal curvature in humans, specifically, the etiopathogenesis of human familial idiopathic scolio...

Vertebral development is a dynamic and complicated process, and defects can be caused by a variety of influences. Spinal curvature with no known cause (idiopathic scoliosis) affects 2-3% of the human population. In order to understand the etiology and pathogenesis of complex human skeletal defects such as idiopathic scoliosis, multiple models must...

Identification of genes that control variation in adaptive characters is a prerequisite for understanding the processes that drive sexual and natural selection. Male coloration and female colour perception play important roles in mate choice in the guppy (Poecilia reticulata), a model organism for studies of natural and sexual selection. We examine...

Well-studied model systems present ideal opportunities to understand the relative roles of contemporary selection versus historical processes in determining population differentiation and speciation. Although guppy populations in Trinidad have been a model for studies of evolutionary ecology and sexual selection for more than 50 years, this work ha...