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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,26]]},"abstract":"<jats:p>\n                    Understanding the processes that link genotype to phenotype is a central challenge in biology. Despite progress in discovering genes associated with ecologically relevant traits, a poor understanding of the processes and functions via which molecules mediate evolutionary differences leaves us critically far from linking proximate and ultimate causes of evolution. This knowledge gap is particularly large in multifaceted phenotypes of ecological relevance such as life histories where multiple traits covary and influence fitness. In Atlantic salmon (\n                    <jats:italic>Salmo salar<\/jats:italic>\n                    ), variation in a key life-history trait, maturation age, is largely linked to the transcription cofactor\n                    <jats:italic>vestigial-like 3<\/jats:italic>\n                    (\n                    <jats:italic>vgll3<\/jats:italic>\n                    ). Here, we show that despite this simple genetic architecture,\n                    <jats:italic>vgll3<\/jats:italic>\n                    genotype influences maturation age through a complex regulatory mechanism whereby it controls the expression of diverse pubertal signaling pathways. Using a multiomic approach in salmon testes, we show that the\n                    <jats:italic>vgll3<\/jats:italic>\n                    genotype conferring early maturity up-regulates key genes controlling androgen production, cellular energy and adiposity, and TGF-\u03b2 signaling, thereby increasing the likelihood of earlier pubertal initiation. By mapping VGLL3 regulatory elements we further show its interaction with distinct transcription factors in a genotype-dependent manner, thus coordinating differential activation of regulatory pathways. This study reveals the proximate mechanisms through which a genetically simple association leads to functionally complex molecular differences in a spectrum of cellular traits, thus explaining the molecular basis of pleiotropy in a large-effect gene. Our results indicate that evolution in correlated phenotypes, as exemplified by alternative life history strategies, can be dictated by the function of major life-history genes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2402386121","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T10:46:41Z","timestamp":1732013201000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["A complex mechanism translating variation of a simple genetic architecture into alternative life histories"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1701-6124","authenticated-orcid":false,"given":"Jukka-Pekka","family":"Verta","sequence":"first","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"},{"name":"Genomics Division, Faculty of Biosciences and Aquaculture, Nord University, Bod\u00f8 8026, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-0945","authenticated-orcid":false,"given":"Jacqueline E.","family":"Moustakas-Verho","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"},{"name":"Natural Resources Institute Finland (LUKE), Helsinki 00790, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iikki","family":"Donner","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9540-6518","authenticated-orcid":false,"given":"Morgane","family":"Frapin","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annukka","family":"Ruokolainen","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4491-9564","authenticated-orcid":false,"given":"Paul V.","family":"Debes","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"},{"name":"Department of Aquaculture and Fish Biology, H\u00f3lar University, Sau\u00f0\u00e1rkr\u00f3kur 551, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Erkinaro","sequence":"additional","affiliation":[{"name":"Natural Resources Institute Finland (LUKE), Helsinki 00790, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-8435","authenticated-orcid":false,"given":"Craig R.","family":"Primmer","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki 00014, Finland"},{"name":"Institute of Biotechnology, Helsinki Institute of Life Sciences, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":"The Genetic Basis of Evolutionary Change","author":"Lewontin R. 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