SimonsEickRuiz-LopezEtAl2017

Reference

Simons, N.D., Eick, G.N., Ruiz-Lopez, M.J., Omeja, P.A., Chapman, C.A., Goldberg, T.L., Ting, N., Sterner, K.N. (2017) Cis-regulatory evolution in a wild primate: Infection-associated genetic variation drives differential expression of MHC-DQA1 in vitro. Molecular Ecology, 26(17):4523-4535. (Scopus )

Abstract

Few studies have combined genetic association analyses with functional characterization of infection-associated SNPs in natural populations of nonhuman primates. Here, we investigate the relationship between host genetic variation, parasitism and natural selection in a population of red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. We collected parasitological, cellular and genomic data to test the following hypotheses: (i) MHC-DQA1 regulatory genetic variation is associated with control of whipworm (Trichuris) infection in a natural population of red colobus; (ii) infection-associated SNPs are functional in driving differential gene expression in vitro; and (iii) balancing selection has shaped patterns of variation in the MHC-DQA1 promoter. We identified two SNPs in the MHC-DQA1 promoter, both in transcription factor binding sites, and both of which are associated with decreased control of Trichuris infection. We characterized the function of both SNPs by testing differences in gene expression between the two alleles of each SNP in two mammalian cell lines. Alleles of one of the SNPs drove differential gene expression in both cell lines, while the other SNP drove differences in expression in one of the cell lines. Additionally, we found evidence of balancing selection acting on the MHC-DQA1 promoter, including extensive trans-species polymorphisms between red colobus and other primates, and an excess of intermediate-frequency alleles relative to genome-wide, coding and noncoding RADseq data. Our data suggest that balancing selection provides adaptive regulatory flexibility that outweighs the consequences of increased parasite infection intensity in heterozygotes. © 2017 John Wiley & Sons Ltd

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@ARTICLE { SimonsEickRuiz-LopezEtAl2017,
    AUTHOR = { Simons, N.D. and Eick, G.N. and Ruiz-Lopez, M.J. and Omeja, P.A. and Chapman, C.A. and Goldberg, T.L. and Ting, N. and Sterner, K.N. },
    TITLE = { Cis-regulatory evolution in a wild primate: Infection-associated genetic variation drives differential expression of MHC-DQA1 in vitro },
    JOURNAL = { Molecular Ecology },
    YEAR = { 2017 },
    VOLUME = { 26 },
    NUMBER = { 17 },
    PAGES = { 4523-4535 },
    NOTE = { cited By 0 },
    ABSTRACT = { Few studies have combined genetic association analyses with functional characterization of infection-associated SNPs in natural populations of nonhuman primates. Here, we investigate the relationship between host genetic variation, parasitism and natural selection in a population of red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. We collected parasitological, cellular and genomic data to test the following hypotheses: (i) MHC-DQA1 regulatory genetic variation is associated with control of whipworm (Trichuris) infection in a natural population of red colobus; (ii) infection-associated SNPs are functional in driving differential gene expression in vitro; and (iii) balancing selection has shaped patterns of variation in the MHC-DQA1 promoter. We identified two SNPs in the MHC-DQA1 promoter, both in transcription factor binding sites, and both of which are associated with decreased control of Trichuris infection. We characterized the function of both SNPs by testing differences in gene expression between the two alleles of each SNP in two mammalian cell lines. Alleles of one of the SNPs drove differential gene expression in both cell lines, while the other SNP drove differences in expression in one of the cell lines. Additionally, we found evidence of balancing selection acting on the MHC-DQA1 promoter, including extensive trans-species polymorphisms between red colobus and other primates, and an excess of intermediate-frequency alleles relative to genome-wide, coding and noncoding RADseq data. Our data suggest that balancing selection provides adaptive regulatory flexibility that outweighs the consequences of increased parasite infection intensity in heterozygotes. © 2017 John Wiley & Sons Ltd },
    AFFILIATION = { Department of Anthropology, University of Oregon, Eugene, OR, United States; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, United States; Makerere University Biological Field Station, Fort Portal, Uganda; Department of Anthropology and McGill School of Environment, McGill University, Montreal, QC, Canada; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United States; Global Health Institute, University of Wisconsin-Madison, Madison, WI, United States },
    AUTHOR_KEYWORDS = { ecoimmunology; immunogenetics; major histocompatibility complex; red colobus; Trichuris },
    DOCUMENT_TYPE = { Article },
    DOI = { 10.1111/mec.14221 },
    SOURCE = { Scopus },
    URL = { https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028073476&doi=10.1111%2fmec.14221&partnerID=40&md5=f5435828a6c49e4a14ca90b05d17a543 },
}

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