Molecular diversity and evolution of HLA genes in Africa (HLA-AFRICA)

Project scope

This project aims at investigating the molecular diversity and evolution of the MHC (HLA) genes involved in adaptive immunity in a large set of human populations in Africa. It will answer the question of whether genetic adaptations to pathogenic environments, which are thought to drive the evolution of MHC genes, have significantly modelled the genetic structure of populations in this continent, which will enlighten our knowledge on the evolutionary mechanisms that marked the history of our species.

To achieve this project, we are generating Third Generation Sequencing (TGS) data for 12 complete HLA genes in 50 African populations of distinct ethnicities, geographic places and ecoregions. We will then carry out a combination of population genetic/genomic and computational approaches, using genome-wide information as a control and taking into account the molecular specificity of each HLA gene/genic region, to explore the patterns of HLA diversity across all of Africa in relation to geographic, demographic, cultural and environmental parameters. We are also producing new TGS data for Patr genes (homologous to HLA) in a cohort of Western chimpanzees to compare the mechanisms that generated MHC diversity in humans with those of their closest relatives.

Project innovations

Africa is at the heart of current debates on modern humans’ evolution and at the same time one of the regions of the world most severely exposed to infectious diseases. On the other hand, very few African populations have been genotyped for HLA at deep molecular levels so far. The results of this study will bring unprecedented information on the mechanisms that drove the evolution of immune genes during the peopling history of this continent. The project will have a main impact in human genomics’ fundamental research by improving our understanding of human molecular variation in both a key region of the genome from a functional point of view, the MHC, and a key region of the world from a human evolutionary point of view, Africa.

Selected publications related to the project

• Černý V., Kulichová I., Poloni ES., Nunes JM., Pereira L., Mayor A., Sanchez-Mazas A. (2018) Genetic history of the African Sahelian populations. HLA. doi: 10.1111/tan.13189. [Epub ahead of print] Review. doi: 10.1111/tan.13189.
• Goeury T., Creary LE., Brunet L., Galan M., Pasquier M., Kervaire B., Langaney A., Tiercy JM., Fernández-Viña MA., Nunes JM., Sanchez-Mazas A. (2018) Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa. HLA 91(1):36-51. doi: 10.1111/tan.13180.
• Sanchez-Mazas A., Černý V., Di D., Buhler S., Podgorná E., Chevallier E., Brunet L., Weber S., Kervaire B., Testi M., Andreani M., Tiercy JM., Villard J., Nunes JM. (2017) The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection. Mol Ecol. 2017; 26:6238-6252. doi: 10.1111/mec.14366.
• Vangenot C., Nunes J.M., Doxiadis G.M., Poloni E.S., Bontrop R.E., De Groot N.G., Sanchez-Mazas A. (2020) Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution. BMC Evol Biol 20, 119. doi: 10.1186/s12862-020-01669-6.