| Grant number: | 12/18010-0 |
| Support Opportunities: | Regular Research Grants |
| Start date: | May 01, 2013 |
| End date: | October 31, 2015 |
| Field of knowledge: | Biological Sciences - Genetics - Human and Medical Genetics |
| Principal Investigator: | Diogo Meyer |
| Grantee: | Diogo Meyer |
| Host Institution: | Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated researchers: | Aida Andrés ; Bruce Spencer Weir ; Eduardo José Melo dos Santos ; Emmanouil Dermitzakis ; Joao Farias Guerreiro ; Jorge Macedo Rocha ; Regina Célia Mingroni Netto |
Abstract
Balancing selection refers to a class of selective regimes that increase genetic variation with respect to neutral expectations. Forms of balancing selection include heterozygote advantage, frequency-dependent selection, and selection which varies over space or time. Although the analysis of genomic data has brought rapid progress to our understanding of how demography and selection interact, our understanding of balancing selection remains comparatively limited. In the present study, we investigate this form of selection using several approaches, with the goal of understanding four main questions. (a) How widespread is balancing selection, and what are its targets? Most scans for selected genes focused on targets of directional selection, but lacked power to detect cases of balancing selection. We propose to use the low coverage sequencing data of 12 human populations made available by the 1000 genomes project to scan the genome for targets of balancing selection. (b) What is the effect of balancing selection on regions near the selected gene? Strong balancing selection is expected to increase linked variation, with the potential of increasing the frequency of linked deleterious variants. Using sequencing data for 12 human populations, we will test this hypothesis by surveying the patterns of polymorphism in regions of the genome close to genes under balancing selection. (c) How does balancing selection shape population differentiation? Although theory predicts that balancing selection will reduce interpopulation differentiation, recent results suggest the opposite may be happening, with selective regimes involving host-pathogen coevolution resulting in high differentiation. Using data from 29 populations with dense genotype data and 12 sequenced populations, in addition to dense genotype data we will generate for four Amerindian populations, we will test this hypothesis by examining genetic differentiation at the loci under the strongest balancing selection yet documented, the classical HLA loci. (d) What is the timescale of balancing selection, and how do selection and admixture interact? Although selection at HLA loci is widely accepted, it is not clear whether it has shaped the recent history of human populations. Using two admixed Brazilian populations, we will compare ancestry proportions in genes under balancing selection (including the strongly selected classical HLA loci) to genome wide averages. Differences in ancestry proportions in recently admixed populations are indicative of recent selection. (AU)
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