{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:20:46Z","timestamp":1761862846627},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2685,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Mapping between genotype and phenotype is one of the primary goals of evolutionary genetics but one that has received little attention at the interspecies level. Recent developments in phylogenetics and statistical modelling have typically been used to examine molecular and phenotypic evolution separately. We have used this background to develop phylogenetic substitution models to test for associations between evolutionary rate of genotype and phenotype. We do this by creating hybrid rate matrices between genotype and phenotype.<\/jats:p>\n               <jats:p>Results: Simulation results show our models to be accurate in detecting genotype\u2013phenotype associations and robust for various factors that typically affect maximum likelihood methods, such as number of taxa, level of relevant signal, proportion of sites affected and length of evolutionary divergence. Further, simulations show that our method is robust to homogeneity assumptions. We apply the models to datasets of male reproductive system genes in relation to mating systems of primates. We show that evolution of semenogelin II is significantly associated with mating systems whereas two negative control genes (cytochrome b and peptidase inhibitor 3) show no significant association. This provides the first hybrid substitution model of which we are aware to directly test the association between genotype and phenotype using a phylogenetic framework.<\/jats:p>\n               <jats:p>Availability: Perl and HYPHY scripts are available upon request from the authors.<\/jats:p>\n               <jats:p>Contact: \u00a0to252@cam.ac.uk<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp231","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T15:48:54Z","timestamp":1243525734000},"page":"i94-i100","source":"Crossref","is-referenced-by-count":33,"title":["Genotype\u2013phenotype associations: substitution models to detect evolutionary associations between phenotypic variables and genotypic evolutionary rate"],"prefix":"10.1093","volume":"25","author":[{"given":"Timothy D.","family":"O'Connor","sequence":"first","affiliation":[{"name":"Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK"}]},{"given":"Nicholas I.","family":"Mundy","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK"}]}],"member":"286","published-online":{"date-parts":[[2009,5,27]]},"reference":[{"key":"2023013111590336600_B1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000064784","article-title":"Sexual selection, seminal coagulation and copulatory plug formation in primates","volume":"73","author":"Dixson","year":"2002","journal-title":"Folia Primatol."},{"key":"2023013111590336600_B2","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/ng1471","article-title":"Rate of molecular evolution of the seminal protein gene SEMG2 correlates with levels of female promiscuity","volume":"6","author":"Dorus","year":"2004","journal-title":"Nat. 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