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

Abstract

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.olfaction ͉ olfactory ͉ molecular evolution ͉ pheromone ͉ GPCR

Mammalian odorant receptors: functional evolution and variation

“…In addition, in a study involving orthologs of Olfr154 (OR912-93) across multiple species, the ligand selectivity of orthologs was found to be similar but not the same: the Olfr154 orthologs of mouse, pig and four primates all responded to both 2- and 3-heptanone, the squirrel-monkey ortholog only responded to 3-heptanone, and the human and orangutan orthologs were not functional [21]. When quantitative characteristics of OR responses were taken into account, primate orthologs of the human OR OR7D4 exhibited extremely diverse potency and efficacy to two steroid ligands, androstenone and androstadienone [22]. Finally, a large scale analysis of 18 OR orthologs in the human, chimpanzee and/or rhesus macaque and of 17 in mouse and rat against a panel of 42 ORs revealed that a striking ~90% of orthologous ORs showed functional variances affecting receptor potency and/or efficacy (Fig 2 A, B).…”

Synthesis of Experimental Molecular Biology and Evolutionary Biology: An Example from the World of Vision

“…When the site-prediction method was applied to the experimental data on opsin genes (Yokoyama et al 2008b) and odorant receptor genes (Zhuang et al 2009), over 90% of the estimates were false positives or false negatives. Moreover, when it was applied to opsin genes, the branch-site method generated equally high rates of false positives and false negatives (Nozawa et al 2009b).…”

Statistical methods for detecting natural selection from genomic data

“…However, it was also reported that the Bayesian method tends to produce excessive false-positives in computer simulation (Suzuki and Nei, 2002;Berlin and Smith, 2005) and real data analysis Nei, 2001, 2004;Friedman and Hughes, 2007). In particular, it was shown from the analysis of rhodopsins and opsins in vertebrates (Hughes, 2008b;Yokoyama et al, 2008;Nozawa et al, 2009a, b) and an odorant receptor in primates (Zhuang et al, 2009) that positively selected sites identified by the Bayesian and Fig. 1.…”