The roles of gene duplication, gene conversion and positive selection in rodent Esp and Mup pheromone gene families with comparison to the Abp family

PLoS One. 2012;7(10):e47697. doi: 10.1371/journal.pone.0047697. Epub 2012 Oct 19.


Three proteinaceous pheromone families, the androgen-binding proteins (ABPs), the exocrine-gland secreting peptides (ESPs) and the major urinary proteins (MUPs) are encoded by large gene families in the genomes of Mus musculus and Rattus norvegicus. We studied the evolutionary histories of the Mup and Esp genes and compared them with what is known about the Abp genes. Apparently gene conversion has played little if any role in the expansion of the mouse Class A and Class B Mup genes and pseudogenes, and the rat Mups. By contrast, we found evidence of extensive gene conversion in many Esp genes although not in all of them. Our studies of selection identified at least two amino acid sites in β-sheets as having evolved under positive selection in the mouse Class A and Class B MUPs and in rat MUPs. We show that selection may have acted on the ESPs by determining K(a)/K(s) for Exon 3 sequences with and without the converted sequence segment. While it appears that purifying selection acted on the ESP signal peptides, the secreted portions of the ESPs probably have undergone much more rapid evolution. When the inner gene converted fragment sequences were removed, eleven Esp paralogs were present in two or more pairs with K(a)/K(s) >1.0 and thus we propose that positive selection is detectable by this means in at least some mouse Esp paralogs. We compare and contrast the evolutionary histories of all three mouse pheromone gene families in light of their proposed functions in mouse communication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Androgen-Binding Protein / genetics*
  • Animals
  • Evolution, Molecular
  • Exons
  • Female
  • Gene Conversion*
  • Gene Duplication*
  • Genome*
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Molecular Sequence Data
  • Multigene Family
  • Pheromones / genetics*
  • Phylogeny
  • Protein Isoforms / genetics
  • Protein Structure, Secondary
  • Proteins / genetics*
  • Rats
  • Selection, Genetic
  • Sequence Homology, Amino Acid
  • Species Specificity


  • Androgen-Binding Protein
  • Intercellular Signaling Peptides and Proteins
  • Pheromones
  • Protein Isoforms
  • Proteins
  • exocrine-gland-secreting peptide 1, mouse
  • major urinary proteins