BackgroundOver the past few years, next-generation sequencing technologies have been developed to characterize ‘adaptive immune receptor repertoires’ (i.e., antibody/B-cell and T-cell receptor ...repertoires or AIRRs) in exquisite detail. AIRR sequencing (AIRR-seq) has enormous promise for understanding the dynamics of the immune repertoire in vaccinology, infectious diseases, autoimmunity, and cancer biology. While AIRR-seq data is important, it is also very large, complex, and requires specialized tools and services to curate, analyze, and share. In response to these challenges, The AIRR Community was formed in 2015 (www.airr-community.org). The AIRR Community comprises immunologists, immunogeneticists, computer scientists, bioinformaticians, and experts in legal, ethics and IP issues who are developing shared protocols and standards to facilitate sharing and analysis of these repertoire data through the AIRR Data Commons (ADC).MethodsThe iReceptor Gateway (www. ireceptor.org) implements the AIRR Data Commons as a network of federated repositories which facilitates data queries and advanced analyses. Secure data repositories, single cell immune profiling, and RNA gene expression and more detailed cell phenotype data for Systems Immunology are being added by the iReceptor Plus consortium, funded by Canadian Institutes of Health Research (CIHR) and the EU Horizon 2020 program.ResultsAs of August 2020, the iReceptor Gateway provides access to 2.7 billion receptor sequences, from 2779 repertoires, and 46 studies; these include 3 B-cell and 10 T-cell cancer studies. These can be queried for specific CDR3 sequences, in order to test whether particular sequences are public (occurring in multiple patients) or private (only found in a few individuals). These can also be queried for specific ‘metadata’, e.g. ‘find all repertoires from studies of ovarian cancer.’ The Gateway aggregates these repertoire data for further analysis by sophisticated AIRR-seq algorithms on HPC resources.ConclusionsAnalysis of aggregated AIRR-seq data through the iReceptor Gateway has great potential to revolutionize many aspects of cancer immunotherapy. The FDA has already approved the use of AIRR-seq data for monitoring clonal expansion as a diagnostic tool in MRD (minimal residual disease). Sequences from tumor specific clones provide targets for monoclonal antibodies in anti-checkpoint therapy and CAR-T cell approaches. Several studies have shown that AIRR-seq data provide biomarkers that partition patients into responders/non-responders and predict those who may exhibit adverse reactions to novel cancer immunotherapies. This potential will be realized as more researchers adopt the AIRR Community standards for sharing and analyzing AIRR-seq data, resulting in more efficient biomedical research and improved patient care.AcknowledgementsFunded by the European Union’s H2020 Research and Innovation Programme under Grant Agreement No. 825821 and Canadian Institutes of Health Research (CIHR)
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.
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 Poecilia reticulata XY system is much older than previously thought, being shared not only with its sister species, Poecilia wingei, but also with Poecilia picta, 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 P. reticulata and P. wingei are largely homomorphic, with recombination in the former persisting over a substantial fraction. However, the sex chromosomes in P. picta are completely nonrecombining and strikingly heteromorphic. Remarkably, the profound degradation of the ancestral Y chromosome in P. picta 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.
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.
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.
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.
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 genomes and consequently very informative for a genome-wide picture of standing natural variation in populations, genome-wide SNP data are rarely available for wild vertebrates. Here we use genetically mapped SNP markers to comprehensively survey genetic variation within and among naturally occurring guppy populations from a wide geographic range in Trinidad and Venezuela. Results from three different clustering methods, Neighbor-net, principal component analysis (PCA) and Bayesian analysis show that the population substructure agrees with geographic separation and largely with previously hypothesized patterns of historical colonization. Within major drainages (Caroni, Oropouche and Northern), populations are genetically similar, but those in different geographic regions are highly divergent from one another, with some indications of ancient shared polymorphisms. Clear genomic signatures of a previous introduction experiment were seen, and we detected additional potential admixture events. Headwater populations were significantly less heterozygous than downstream populations. Pairwise FST values revealed marked differences in allele frequencies among populations from different regions, and also among populations within the same region. FST outlier methods indicated some regions of the genome as being under directional selection. Overall, this study demonstrates the power of a genome-wide SNP data set to inform for studies on natural variation, adaptation and evolution of wild populations
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.
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.
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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