Tests for positive selection on immune and reproductive genes in closely related species of the murine genus Mus

Sharon A. Jansa, Barbara L. Lundrigan, Priscilla K. Tucker

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52 Scopus citations

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 β2m. 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 β2m, 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 β2m 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.

Original languageEnglish (US)
Pages (from-to)294-307
Number of pages14
JournalJournal of Molecular Evolution
Volume56
Issue number3
DOIs
StatePublished - Mar 1 2003

Keywords

  • Mus
  • Positive selection
  • Sry
  • Tcp-1
  • Zona pellucida
  • Zp-3
  • β-2-Microglobulin

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