{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:03:34Z","timestamp":1792735414829,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,2,28]]},"abstract":"<jats:p>\n                    The unprecedented genetic diversity found at vertebrate\n                    <jats:italic>MHC<\/jats:italic>\n                    (major histocompatibility complex) loci influences susceptibility to most infectious and autoimmune diseases. The evolutionary explanation for how these polymorphisms are maintained has been controversial. One leading explanation, antagonistic coevolution (also known as the Red Queen), postulates a never-ending molecular arms race where pathogens evolve to evade immune recognition by common\n                    <jats:italic>MHC<\/jats:italic>\n                    alleles, which in turn provides a selective advantage to hosts carrying rare\n                    <jats:italic>MHC<\/jats:italic>\n                    alleles. This cyclical process leads to negative frequency-dependent selection and promotes\n                    <jats:italic>MHC<\/jats:italic>\n                    diversity if two conditions are met: (\n                    <jats:italic>i<\/jats:italic>\n                    ) pathogen adaptation must produce trade-offs that result in pathogen fitness being higher in familiar (i.e., host\n                    <jats:italic>MHC<\/jats:italic>\n                    genotype adapted to) vs. unfamiliar host\n                    <jats:italic>MHC<\/jats:italic>\n                    genotypes; and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) this adaptation must produce correlated patterns of virulence (i.e., disease severity). Here we test these fundamental assumptions using an experimental evolutionary approach (serial passage). We demonstrate rapid adaptation and virulence evolution of a mouse-specific retrovirus to its mammalian host across multiple\n                    <jats:italic>MHC<\/jats:italic>\n                    genotypes. Critically, this adaptive response results in trade-offs (i.e., antagonistic pleiotropy) between host\n                    <jats:italic>MHC<\/jats:italic>\n                    genotypes; both viral fitness and virulence is substantially higher in familiar versus unfamiliar\n                    <jats:italic>MHC<\/jats:italic>\n                    genotypes. These data are unique in experimentally confirming the requisite conditions of the antagonistic coevolution model of\n                    <jats:italic>MHC<\/jats:italic>\n                    evolution and providing quantification of fitness effects for pathogen and host. These data help explain the unprecedented diversity of\n                    <jats:italic>MHC<\/jats:italic>\n                    genes, including how disease-causing alleles are maintained.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1112633109","type":"journal-article","created":{"date-parts":[[2012,2,8]],"date-time":"2012-02-08T00:58:49Z","timestamp":1328662729000},"page":"3422-3427","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["Experimental viral evolution to specific host\n                    <i>MHC<\/i>\n                    genotypes reveals fitness and virulence trade-offs in alternative\n                    <i>MHC<\/i>\n                    types"],"prefix":"10.1073","volume":"109","author":[{"given":"Jason L.","family":"Kubinak","sequence":"first","affiliation":[{"name":"Department of Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Department of Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius Whitney","family":"Hyzer","sequence":"additional","affiliation":[{"name":"Department of Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia R.","family":"Slev","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne K.","family":"Potts","sequence":"additional","affiliation":[{"name":"Department of Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,2,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq998"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v17.i2.40"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/303166"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2009.2084"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ecolsys.37.091305.110242"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/124.4.967"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-003-0629-y"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6800724"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-003-0630-5"},{"key":"e_1_3_3_10_2","first-page":"68","article-title":"Disease and evolution","volume":"19","author":"Haldane JBS","year":"1949","unstructured":"JBS Haldane, Disease and evolution. 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