Demographic history and selection at HLA loci in Native Americans

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Single, Richard M. ^[1] ; Meyer, Diogo ^[2] ; Nunes, Kelly ^[2] ; Francisco, Rodrigo Santos ^[2] ; Hunemeier, Tabita ^[2] ; Maiers, Martin ^[3] ; Hurley, Carolyn K. ^[4] ; Bedoya, Gabriel ^[5] ; Gallo, Carla ^[6] ; Hurtado, Ana Magdalena ^[7] ; Llop, Elena ^[8] ; Petzl-Erler, Maria Luiza ^[9] ; Poletti, Giovanni ^[10] ; Rothhammer, Francisco ^{[8, 11]} ; Tsuneto, Luiza ^[12] ; Klitz, William ^[13] ; Ruiz-Linares, Andres ^{[14, 15, 16]}

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^[1] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 - USA

^[2] Univ Sao Paulo, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[3] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN - USA

^[4] Georgetown Univ, CW Bill Young Marrow Donor Recruitment & Res Prog, Washington, DC - USA

^[5] Univ Antioquia Medellin, Inst Biol, Medellin - Colombia

^[6] Univ Peruana Cayetano Heredia, Labs Invest & Desarrollo, Lima - Peru

^[7] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ - USA

^[8] Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Genet Humana, Santiago - Chile

^[9] Univ Fed Parana, Dept Genet, Curitiba, Parana - Brazil

^[10] Univ Peruana Cayetano Heredia, Fac Med, Lima - Peru

^[11] Tarapaca Univ, Inst Alta Invest, Arica - Chile

^[12] Univ Estadual Maringa, Dept Basic Hlth Sci, Maringa, Parana - Brazil

^[13] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 - USA

^[14] Fudan Univ, Key Lab Contemporary Anthropol, Sch Life Sci & Human Phenome Inst, Minist Educ, Shanghai - Peoples R China

^[15] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci & Human Phenome Inst, Shanghai - Peoples R China

^[16] D Aix Marseille Univ, ADES, EFS, CNRS, Marseille - France

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 15, n. 11 NOV 4 2020.
• Citações Web of Science: 0

Resumo

The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers. (AU)

• Processo FAPESP: 12/18010-0 - Seleção balanceadora no genoma humano: detecção, causas e consequências
• Beneficiário: Diogo Meyer
• Modalidade de apoio: Auxílio à Pesquisa - Regular