ArticleProceedings. Biological sciences2009
A new theory of MHC evolution: beyond selection on the immune genes.
Article in Proceedings. Biological sciences, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 148 citations in OpenAlex.
- Genomic erosion in the assessment of species' extinction risk and recovery potential.The Journal of heredity · 2026Article
- Research Progress on the Major Histocompatibility Complex in Herbivores: Structure, Genetics, and Disease Resistance.Biology · 2026Review
- Associations among MHC genes, latitude, and avian malaria infections in the rufous-collared sparrow (Ecology and evolution · 2024Article
- Article
- Human leukocyte antigen super-locus: nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes.Human genome variation · 2022Review
- The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering.International journal of molecular sciences · 2022Review
- Intronic primers reveal unexpectedly high major histocompatibility complex diversity in Antarctic fur seals.Scientific reports · 2022Article
- Genetic load: genomic estimates and applications in non-model animals.Nature reviews. Genetics · 2022Review
- Using de novo genome assembly and high-throughput sequencing to characterize the MHC region in a non-model bird, the Eurasian coot.Scientific reports · 2022Article
- Functional immunogenetic variation, rather than local adaptation, predicts ectoparasite infection intensity in a model fish species.Molecular ecology · 2021Article
- How natural selection shapes genetic differentiation in the MHC region: A case study with Native Americans.Human immunology · 2021Article
- Haplotype Shuffling and Dimorphic Transposable Elements in the Human Extended Major Histocompatibility Complex Class II Region.Frontiers in genetics · 2021Article
- An alternative route of bacterial infection associated with a novel resistance locus in the Daphnia-Pasteuria host-parasite system.Heredity · 2020Article
- Allelic diversity and patterns of selection at the major histocompatibility complex class I and II loci in a threatened shorebird, the Snowy Plover (Charadrius nivosus).BMC evolutionary biology · 2020Article
- Mating preferences can drive expansion or contraction of major histocompatibility complex gene family.Proceedings. Biological sciences · 2020Article
- SNP-Density Crossover Maps of Polymorphic Transposable Elements and HLA Genes Within MHC Class I Haplotype Blocks and Junction.Frontiers in genetics · 2020Article
- Not all birds have a single dominantly expressed MHC-I gene: Transcription suggests that siskins have many highly expressed MHC-I genes.Scientific reports · 2019Article
- Evolution of the human MHC: New haplotype frequency analysis is not informative.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Multiplicative fitness, rapid haplotype discovery, and fitness decay explain evolution of human MHC.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- On the Population Dynamics of Junk: A Review on the Population Genomics of Transposable Elements.Genes · 2019Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The major histocompatibility complex (MHC) is a dense region of immune genes with high levels of polymorphism, which are arranged in haplotype blocks. Traditional models of balancing selection (i.e. overdominance and negative frequency dependence) were developed to study the population genetics of single genes. However, the MHC is a multigene family surrounded by linked (non-neutral) polymorphisms, and not all of its features are well explained by these models. For example, (i) the high levels of polymorphism in small populations, (ii) the unexpectedly large genetic differentiation between populations, (iii) the shape of the allelic genealogy associated with trans-species evolution, and (iv) the close associations between particular MHC (human leucocyte antigen, HLA) haplotypes and the approximately 100 pathologies in humans. Here, I propose a new model of MHC evolution named Associative Balancing Complex evolution that can explain these phenomena. The model proposes that recessive deleterious mutations accumulate as a 'sheltered load' nearby MHC genes. These mutations can accumulate because (i) they are rarely expressed as homozygotes given the high MHC gene diversity and (ii) purifying selection is inefficient with low recombination rates (cf. Muller's ratchet). Once fixed, these mutations add to balancing selection and further reinforce linkage through epistatic selection against recombinants.
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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.