{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:29:45Z","timestamp":1789820985983,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["22133007"],"award-info":[{"award-number":["22133007"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tissue Antigens"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic diversity in human leukocyte antigen (<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>) molecules is thought to have arisen from the co\u2010evolution between host and pathogen and maintained by balancing selection. Heterozygote advantage is a common proposed scenario for maintaining high levels of diversity in <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> genes, and extending from this, the divergent allele advantage (<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>) model suggests that individuals with more divergent <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> alleles bind and recognize a wider array of antigens. While the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> model seems biologically suitable for driving <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> diversity, there is likely an upper threshold to the amount of sequence divergence. We used peptide\u2010binding and pathogen\u2010recognition capacity of <jats:italic><jats:styled-content style=\"fixed-case\">DRB1<\/jats:styled-content><\/jats:italic> alleles as a model to further explore the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> model; within the <jats:italic><jats:styled-content style=\"fixed-case\">DRB1<\/jats:styled-content><\/jats:italic> locus, we examined binding predictions based on two distinct phylogenetic groups (denoted group A and B) previously identified based on non\u2010peptide\u2010binding region (<jats:styled-content style=\"fixed-case\">PBR<\/jats:styled-content>) nucleotide sequences. Predictions in this study support that group A allele and group B allele lineages have contrasting binding\/recognition capacity, with only the latter supporting the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> model. Furthermore, computer simulations revealed an inconsistency in the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> model alone with observed extent of polymorphisms, supporting that the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> model could only work effectively in combination with other mechanisms. Overall, we support that the mechanisms driving <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> diversity are non\u2010exclusive. By investigating the relationships among <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> alleles, and pathogens recognized, we can provide further insights into the mechanisms on how humans have adapted to infectious diseases over time.<\/jats:p>","DOI":"10.1111\/tan.12667","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T10:15:15Z","timestamp":1442916915000},"page":"343-352","source":"Crossref","is-referenced-by-count":13,"title":["A limit to the divergent allele advantage model supported by variable pathogen recognition across HLA\u2010DRB1 allele lineages"],"prefix":"10.1111","volume":"86","author":[{"given":"Q.","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Evolutionary Studies of Biosystems Sokendai (The Graduate University for Advanced Studies)  Kanagawa 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