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Natural selection on the X chromosome of human populations

Grant number: 19/11647-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Diogo Meyer
Grantee:Carlos Henrique Passos
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

With the increasing availability of human genomic data, it has became possible to identify genes under natural selection, including those associated to pathogen resistance, climatic adaptation or change in diet. However, such studies have prioritized autosomes, with the effects of natural selection acting on the X chromosome remaining poorly studied. The X chromosome is enriched for genes related to fertility, neurologic functions, and associated with diseases, including some degenerative disorders and forms of cancer. In addition, mutations on the X chromosome are immediately exposed to natural selection when present in hemizigous men. Together, these characteristics make the X chromosome an important target for studies about selection in the human genome. Our goal in this project is to study the action of natural selection that occurs in different time scales on the X chromosome, specifically: (I) contemporary selection, occurring in the current generation; (II) recent selection, occurring over the most recent hundreds of years, since the beginning of admixture between Europeans, Africans and native Americans in the Brazilian gene pool; and (III) intermediate selection, taking place over thousands of years, generating differences between populations present in different continents. Our analytical strategies to detect selection are: (I) comparison of the SNP frequency in males and females (contemporary selection); (II) detection of genomic regions with deviations in the proportions of ancestry (recent selection); and (III) detection of regions with SNPs with extreme differentiation, measured by FST values (intermediary selection). Through this study we hope to better understand the role of ploidy modulating the intensity and dynamics of natural selection, to identify new targets of selection in humans, and to understand how natural selection (as well our ability to detect it) differs according to the time scale investigated.

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