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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Brandt, Debora Y. C. [1, 2] ; Cesar, Jonatas [2] ; Goudet, Jerome [3, 4] ; Meyer, Diogo [2]
Total Authors: 4
[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
Total Affiliations: 4
Document type: Journal article
Source: G3-GENES, GENOMES, GENETICS; v. 8, n. 8, p. 2805-2815, AUG 2018.
Web of Science Citations: 4

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)

FAPESP's process: 15/19990-6 - Uncovering rare variants in HLA genes: evolutionary analysis and impact on genetic load
Grantee:Jônatas Eduardo da Silva César
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/12162-5 - Balancing selection and population differentiation on HLA genes
Grantee:Débora Yoshihara Caldeira Brandt
Support type: Scholarships abroad - Research Internship - Master's degree
FAPESP's process: 12/18010-0 - Balancing selection in the human genome: detection, causes and consequences
Grantee:Diogo Meyer
Support type: Regular Research Grants
FAPESP's process: 12/22796-9 - Population differentiation on genes under strong balancing selection: a case study on the HLA genes
Grantee:Débora Yoshihara Caldeira Brandt
Support type: Scholarships in Brazil - Master