ArticleMolecular biology and evolution2021
Like Wings of a Bird: Functional Divergence and Complementarity between HLA-A and HLA-B Molecules.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Genetic overlap and causality between depression and preterm birth: a large-scale genome-wide cross-trait analysis.Psychological medicine · 2025Pooled it
- Structural evolution of polymorphic class I HLA alleles, designating HLA-C with uncertain assemblies.Computational and structural biotechnology journal · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Genetic and environmental imprints on T cell receptor repertoires as predictors of graft-versus-host disease.bioRxiv : the preprint server for biology · 2025Article
- Quantitative and large-scale investigation of human TCR-HLA cross-reactivity.Science advances · 2025Article
- In Situ Detection of Individual Classic MHC-I Gene Products in Cancer.Cancer immunology research · 2025Article
- Evidence for Pathogen-Driven Selection Acting onEcology and evolution · 2025Article
- Toripalimab plus chemotherapy as first-line treatment in extensive-stage small cell lung cancer: a health economic evaluation in China.Frontiers in public health · 2025Article
- Exploration of biomarkers associated with histone lactylation modification in spinal cord injury.Frontiers in genetics · 2025Article
- Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Impact of HLA class I functional divergence on HIV control.Science (New York, N.Y.) · 2024Article
- An HLA map of the world: A comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II.Frontiers in genetics · 2023Article
- Challenging Ancient DNA Results About Putative HLA Protection or Susceptibility to Yersinia pestis.Molecular biology and evolution · 2022Article
- Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral-Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People.Frontiers in immunology · 2022Article
- Unique Pathogen Peptidomes Facilitate Pathogen-Specific Selection and Specialization of MHC Alleles.Molecular biology and evolution · 2021Article
- Approaching Genetics Through the MHC Lens: Tools and Methods for HLA Research.Frontiers in genetics · 2021Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.