title: Tests for positive selection on immune and reproductive genes in closely related species of the murine genus mus.
abstract: We examine variation among species of Mus in four genes involved in reproduction and the immune response for evidence of positive selection: the sperm recognition gene Zp-3, the testis-determining locus Sry, the testicular cell surface matrix protein Tcp-1, and the immune system protein beta(2) m. We use likelihood ratio tests in the context of a well-supported phylogeny to determine whether models that allow for positively selected sites fit the sequences better than models that assume purifying selection. We then apply a Bayesian approach to identify particular sites in each gene that have a high posterior probability of being under positive selection. We find no evidence of positive selection on the Tcp-1 gene, but for Zp-3, Sry, and beta(2) m, models that allow for positively selected sites fit the sequences better than alternatives. For each of these genes, we identify sites that have a high (> 95%) posterior probability of being positively selected. For Zp-3, two of these sites occur near the sperm-binding region, while one occurs in a region whose functional role remains unstudied but where the pattern of change predicts functional importance. A single site in Sry shows an elevated rate of replacement substitution but occurs in a region of apparently little functional importance; therefore, relaxation of functional constraints may better explain the rapid evolution of this site. Three sites in beta(2) m have a posterior probability > 50% of being under positive selection. While the functional role for two of these sites is unknown, the third is known to influence the ability of MHC class I molecules to present antigens to the immune system; therefore, the elevated rate of replacement substitutions at this site is consistent with selection acting to promote variability in immune system proteins.
authors.affiliation: Department of Ecology, Evolution, and Behavior, University of Minnesota, St Paul, MN 55108-6098, USA. jansa003@tc.umn. edu
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Jansa
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Lundrigan
authors.forename: Priscilla K
authors.initials: PK
authors.lastname: Tucker
mesh_terms: D000818:Animals; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004527:Egg Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009115:Muridae / Q000235:genetics* / Q000276:immunology; D009687:Nuclear Proteins; D010802:Phylogeny; D011956:Receptors, Cell Surface; D012641:Selection, Genetic; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D000072216:Zona Pellucida Glycoproteins; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D014157:Transcription Factors; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; D001613:beta 2-Microglobulin; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins