Dynamic functional evolution of an odorant receptor for sex-steroid-derived odors in primates

Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21247-51. doi: 10.1073/pnas.0808378106. Epub 2009 Dec 2.


Odorant receptors are among the fastest evolving genes in animals. However, little is known about the functional changes of individual odorant receptors during evolution. We have recently demonstrated a link between the in vitro function of a human odorant receptor, OR7D4, and in vivo olfactory perception of 2 steroidal ligands--androstenone and androstadienone--chemicals that are shown to affect physiological responses in humans. In this study, we analyzed the in vitro function of OR7D4 in primate evolution. Orthologs of OR7D4 were cloned from different primate species. Ancestral reconstruction allowed us to reconstitute additional putative OR7D4 orthologs in hypothetical ancestral species. Functional analysis of these orthologs showed an extremely diverse range of OR7D4 responses to the ligands in various primate species. Functional analysis of the nonsynonymous changes in the Old World Monkey and Great Ape lineages revealed a number of sites causing increases or decreases in sensitivity. We found that the majority of the functionally important residues in OR7D4 were not predicted by the maximum likelihood analysis detecting positive Darwinian selection.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cercopithecidae
  • Evolution, Molecular*
  • Gonadal Steroid Hormones / metabolism
  • Gonadal Steroid Hormones / physiology*
  • Hominidae
  • Humans
  • Ligands
  • Likelihood Functions
  • Molecular Sequence Data
  • Primates
  • Receptors, Odorant / genetics
  • Receptors, Odorant / physiology
  • Receptors, Pheromone / genetics*
  • Receptors, Pheromone / metabolism
  • Receptors, Pheromone / physiology
  • Selection, Genetic
  • Smell / genetics*


  • Gonadal Steroid Hormones
  • Ligands
  • Receptors, Odorant
  • Receptors, Pheromone

Associated data

  • GENBANK/GU139530
  • GENBANK/GU139531
  • GENBANK/GU139532
  • GENBANK/GU139533
  • GENBANK/GU139534
  • GENBANK/GU139535
  • GENBANK/GU139536
  • GENBANK/GU139537
  • GENBANK/GU139538
  • GENBANK/GU139539
  • GENBANK/GU139540
  • GENBANK/GU139541
  • GENBANK/GU139542
  • GENBANK/GU139543
  • GENBANK/GU139544