Natural selection in the MHC region of human populations

• Grant number: 25/15750-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Diogo Meyer
• Grantee: Jennifer Eliana Montoya Neyra
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/14851-9 - Human Population Genomics: a view from admixed populations, AP.TEM

Abstract

We will implement statistical tests designed to identify deviation from backgroundancestry within the MHC region (Grinde et al. 2019). Local ancestry will be estimated usingRFMIX (Maples et al. 2013) or other methods that may be developed during the fundingperiod. We will use simulations to evaluate the robustness of local ancestry estimation in theMHC. To do so, we will use forward simulations to model populations evolving under neutralconditions, but with source populations with high heterozygosity (thus mimicking potentialbiases associated to the MHC region). Our strategy relies on identifying HLA alleles in theadmixed populations and carrying out tests for recent selection to identify putatively selectedvariants. To identify recently selected alleles we will use tests based on linkagedisequilibrium flanking the HLA loci (e.g., integrated haplotype homozygosity, iHS) (Szpiechand Hernandez 2014), which will also provide an estimate of the timescale of selection onthe HLA loci, allowing us to distinguish between the role of recent selection (post-admixture)from that which took place in Africa. Finally, using a simulation-based framework (Haller andMesser 2019) , we will explore a theoretical model of selection, according to which the highpolymorphism of African populations explains the selective advantage of African alleles.