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

J Mol Evol. 2003 Mar;56(3):294-307. doi: 10.1007/s00239-002-2401-6.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chaperonin Containing TCP-1
  • Chaperonins / genetics
  • DNA-Binding Proteins / genetics
  • Egg Proteins / genetics
  • Membrane Glycoproteins / genetics
  • Mice
  • Muridae / genetics*
  • Muridae / immunology
  • Nuclear Proteins*
  • Phylogeny
  • Receptors, Cell Surface*
  • Selection, Genetic*
  • Sex-Determining Region Y Protein
  • Transcription Factors*
  • Zona Pellucida Glycoproteins
  • beta 2-Microglobulin / genetics


  • DNA-Binding Proteins
  • Egg Proteins
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Receptors, Cell Surface
  • Sex-Determining Region Y Protein
  • Sry protein, mouse
  • Transcription Factors
  • Zona Pellucida Glycoproteins
  • Zp3 protein, mouse
  • beta 2-Microglobulin
  • Chaperonin Containing TCP-1
  • Chaperonins