Dataset Information

Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism.

ABSTRACT: Trans-species polymorphism has been widely used as a key sign of long-term balancing selection across multiple species. However, such sites are often rare in the genome and could result from mutational processes or technical artifacts. Few methods are yet available to specifically detect footprints of trans-species balancing selection without using trans-species polymorphic sites. In this study, we develop summary- and model-based approaches that are each specifically tailored to uncover regions of long-term balancing selection shared by a set of species by using genomic patterns of intraspecific polymorphism and interspecific fixed differences. We demonstrate that our trans-species statistics have substantially higher power than single-species approaches to detect footprints of trans-species balancing selection, and are robust to those that do not affect all tested species. We further apply our model-based methods to human and chimpanzee whole-genome sequencing data. In addition to the previously established major histocompatibility complex and malaria resistance-associated FREM3/GYPE regions, we also find outstanding genomic regions involved in barrier integrity and innate immunity, such as the GRIK1/CLDN17 intergenic region, and the SLC35F1 and ABCA13 genes. Our findings not only echo the significance of pathogen defense but also reveal novel candidates in maintaining balanced polymorphisms across human and chimpanzee lineages. Finally, we show that these trans-species statistics can be applied to and work well for an arbitrary number of species, and integrate them into open-source software packages for ease of use by the scientific community.

SUBMITTER: Cheng X

PROVIDER: S-EPMC6530816 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism.

Cheng Xiaoheng X DeGiorgio Michael M

Molecular biology and evolution 20190101 1

Trans-species polymorphism has been widely used as a key sign of long-term balancing selection across multiple species. However, such sites are often rare in the genome and could result from mutational processes or technical artifacts. Few methods are yet available to specifically detect footprints of trans-species balancing selection without using trans-species polymorphic sites. In this study, we develop summary- and model-based approaches that are each specifically tailored to uncover regions ...[more]

PMID: 30380122

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Project description:Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the induction of protective immunity.

Dataset Information

Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism.

Publications

Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism.

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