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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes

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Autor(es):
Brandt, Debora Y. C. [1, 2] ; Cesar, Jonatas [2] ; Goudet, Jerome [3, 4] ; Meyer, Diogo [2]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 - USA
[2] Univ Sao Paulo, Dept Genet & Biol Evolut, Sao Paulo, SP - Brazil
[3] Univ Lausanne, Dept Ecol & Evolut, Lausanne - Switzerland
[4] Univ Lausanne, Swiss Inst Bioinformat, Lausanne - Switzerland
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: G3-GENES, GENOMES, GENETICS; v. 8, n. 8, p. 2805-2815, AUG 2018.
Citações Web of Science: 3
Resumo

Balancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by F-ST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle the connection between balancing selection and population differentiation, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. We show that these results require using a computation that accounts for the dependence of F-ST on allele frequencies. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. Such increased population differentiation at HLA genes for recently diverged population pairs was reproduced in simulations of overdominant selection, as long as the fitness of the homozygotes differs between the diverging populations. The results give insight into a possible ``divergent overdominance{''} mechanism for the nature of balancing selection on HLA genes across human populations. (AU)

Processo FAPESP: 15/19990-6 - Descobrindo variantes raras nos genes HLA: análise evolutiva e impacto sobre carga genética
Beneficiário:Jônatas Eduardo da Silva César
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/22796-9 - Diferenciação populacional em genes sob forte seleção balanceadora: um estudo de caso com genes HLA
Beneficiário:Débora Yoshihara Caldeira Brandt
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 12/18010-0 - Seleção balanceadora no genoma humano: detecção, causas e consequências
Beneficiário:Diogo Meyer
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/12162-5 - Seleção balanceadora e diferenciação populacional em genes HLA
Beneficiário:Débora Yoshihara Caldeira Brandt
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Mestrado