ArticleProceedings of the National Academy of Sciences of the United States of America2013
Pathogen selection drives nonoverlapping associations between HLA loci.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Negative Frequency-Dependent Selection Promotes Strain Structure in a Plant Pathogen.Ecology letters · 2026Article
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- Coevolutionary theory of hosts and parasites.Journal of evolutionary biology · 2022Review
- Comparing raccoon major histocompatibility complex diversity in native and introduced ranges: Evidence for the importance of functional immune diversity for adaptation and survival in novel environments.Evolutionary applications · 2020Article
- Diversity of HLA Class I and Class II blocks and conserved extended haplotypes in Lacandon Mayans.Scientific reports · 2020Article
- Semen quality is affected by HLA class I alleles together with sexually transmitted diseases.Andrology · 2019Article
- Models of immune selection for multi-locus antigenic diversity of pathogens.Nature reviews. Immunology · 2019Review
- A genomic perspective on HLA evolution.Immunogenetics · 2018Review
- Host-parasite fluctuating selection in the absence of specificity.Proceedings. Biological sciences · 2017Article
- Competing species leave many potential niches unfilled.Nature ecology & evolution · 2017Article
- Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection.Molecular biology and evolution · 2016Article
- MANTIS: an R package that simulates multilocus models of pathogen evolution.BMC bioinformatics · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host-pathogen systems.
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Registered trials
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.