Population differentiation on genes under strong balancing selection: a case study on the HLA genes

• Grant number: 12/22796-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2013
• End date: January 31, 2015
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Débora Yoshihara Caldeira Brandt
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 13/12162-5 - Balancing selection and population differentiation on HLA genes, BE.EP.MS

Abstract

Neutral and selective forces act on genetic variation within and between populations, and these processes leave signatures on the genomic regions they act on. Balancing selection is defined as an evolutionary process that raises genetic variability relative to what would be expected under genetic drift. It is usually assumed that balancing selection reduces population differentiation, but selective regimes that maintain different sets of alleles in different populations could also result in higher levels of population differentiation. This project aims to investigate the pattern of population differentiation on the HLA genes, comparing it to genome-wide population differentiation. There is robust evidence that HLA genes, which play a fundamental role in the immune system, are under balancing selection: high genetic diversity, high linkage disequilibrium, higher non-synonymous than synonymous substitution rates, and transspecific polymorphism. Our hypothesis is that pathogens are the natural selection on those genes. This kind of selective pressure varies over space, because different environments host different sets of pathogens. Therefore, the action of balancing selection on the HLA genes would be expected to raise genetic differentiation among populations at these loci. We thus expect the average differentiation among human populations to be higher on HLA genes than other genomic regions. We also expect populations which share a similar set of pathogens to be less differentiated at these loci than those which share fewer pathogens. To test these hypotheses, we will use publicly available datasets of population variation on HLA genes, as well as datasets of SNPs dispersed on the genome, in several human populations from different parts of the world. These will allow us to perform statistical tests on the hypothesis that there are significant differences on population differentiation at HLA genes, relative to other genomic regions. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRANDT, DEBORA Y. C.; CESAR, JONATAS; GOUDET, JEROME; MEYER, DIOGO. The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes. G3-GENES, GENOMES, GENETICS, v. 8, n. 8, p. 2805-2815, AUG 2018. (15/19990-6, 12/18010-0, 13/12162-5, 12/22796-9)

MEYER, DIOGO; AGUIAR, VITOR R. C.; BITARELLO, BARBARA D.; BRANDT, DEBORA Y. C.; NUNES, KELLY. A genomic perspective on HLA evolution. IMMUNOGENETICS, v. 70, n. 1, p. 5-27, JAN 2018. (12/18010-0, 11/12500-2, 14/12123-2, 12/22796-9, 12/09950-9)

BRANDT, DEBORA Y. C.; AGUIAR, VITOR R. C.; BITARELLO, BARBARA D.; NUNES, KELLY; GOUDET, JEROME; MEYER, DIOGO. Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data. G3-GENES, GENOMES, GENETICS, v. 5, n. 5, p. 931-941, MAY 1 2015. (12/18010-0, 11/12500-2, 13/12162-5, 14/12123-2, 12/22796-9, 12/09950-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BRANDT, Débora Yoshihara Caldeira. Population differentiation at genes under strong balancing selection: a case study on the HLA genes. 2015. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.