Scientific article
Open access

Like Wings of a Bird: Functional Divergence and Complementarity between HLA-A and HLA-B Molecules

Published inMolecular biology and evolution, vol. 38, no. 4, p. 1580-1594
Publication date2021
First online date2020-12-15

Human leukocyte antigen (HLA) genes are among the most polymorphic of our genome, as a likely consequence of balancing selection related to their central role in adaptive immunity. HLA-A and HLA-B genes were recently suggested to evolve through a model of joint divergent asymmetric selection conferring all human populations, including those with severe loss of diversity, an equivalent immune potential. However, the mechanisms by which these two genes might undergo joint evolution while displaying very distinct allelic profiles in populations are still unknown. To address this issue, we carried out extensive data analyses (among which factorial correspondence analysis and linear modeling) on 2,909 common and rare HLA-A, HLA-B, and HLA-C alleles and 200,000 simulated pathogenic peptides by taking into account sequence variation, predicted peptide-binding affinity and HLA allele frequencies in 123 populations worldwide. Our results show that HLA-A and HLA-B (but not HLA-C) molecules maintain considerable functional divergence in almost all populations, which likely plays an instrumental role in their immune defense. We also provide robust evidence of functional complementarity between HLA-A and HLA-B molecules, which display asymmetric relationships in terms of amino acid diversity at both inter- and intraprotein levels and in terms of promiscuous or fastidious peptide-binding specificities. Like two wings of a flying bird, the functional complementarity of HLA-A and HLA-B is a perfect example, in our genome, of duplicated genes sharing their capacity of assuming common vital functions while being submitted to complex and sometimes distinct environmental pressures.

  • HLA allele frequencies
  • HLA diversity
  • HLA duplicated genes
  • Balancing selection
  • Functional complementarity
  • Peptide-binding predictions
Citation (ISO format)
DI, Da et al. Like Wings of a Bird: Functional Divergence and Complementarity between HLA-A and HLA-B Molecules. In: Molecular biology and evolution, 2021, vol. 38, n° 4, p. 1580–1594. doi: 10.1093/molbev/msaa325
Main files (1)
Article (Published version)
ISSN of the journal0737-4038

Technical informations

Creation05/14/2024 3:52:01 PM
First validation05/15/2024 9:53:42 AM
Update time05/22/2024 1:21:15 PM
Status update05/22/2024 1:21:15 PM
Last indexation05/22/2024 1:21:20 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack