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How balancing selection shapes population differentiation: a genomic study

Grant number: 19/11593-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2020
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Diogo Meyer
Grantee:André Silva Maróstica
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Natural selection may shape population differentiation, increasing (directional selection) or decreasing it (balancing selection) relative to neutral expectations. Beyond these general expectations, little is known about how balancing selection-selection that increases variability within a population-affects population differentiation. This difficulty is explained by the fact that balancing selection is defined by its effects on genetic diversity, without specifying a specific microevolutionary mechanism. Thus, "balancing selection" includes regimes as diverse as heterozygote advantage, frequency-dependent selection, and selection varying over time and space. Consequently, it is hard to generalize its effect on population differentiation. Faced with this challenge, our group has used simulations and empirical analyses to investigate the impact of balancing selection on differentiation at HLA genes, showing that asymmetric heterozygote advantage can increase population differentiation, a finding that contrasts with the intuition that balancing selection reduces differentiation. However, our previous studies were limited to the analysis of HLA genes and to the modelling of just one selective regime. In the present project, we propose to combine both empirical and simulation approaches to investigate how balancing selection shapes population differentiation in a larger set of genes for which balancing selection has been documented, and carrying out modelling for several regimes of balancing selection. Initially, we will test the hypothesis that differentiation for genes under balancing selection differs from that expected under neutrality. Next, we will simulate different forms of heterozygote advantage and frequency-dependent selection, in order to determine which regimes are capable of producing differentiation patterns similar to those observed in the empirical data. With this combination of strategies, we seek to understand how balancing selection shapes population differentiation and which balancing selection regimes are capable of generating population differentiation similar to those observed in human populations. (AU)