Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates

Abstract

The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human-mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors.

Fig. 1

Distribution of olfactory receptor (OR) genes in human chromosomes. Vertical bars above and below the chromosomes indicate locations of OR functional genes and pseudogenes respectively. The height of each bar represents the number of OR genes in a non-overlapping 500-kb window at the position. Chromosomes 20 and Y are omitted, because OR genes were not found in these chromosomes. Modified from Niimura and Nei (2003)

Fig. 2

a Neighbor-joining (NJ) phylogenetic tree of 388 human functional OR genes constructed by using Poisson correction distances (Nei and Kumar 2000) for all pairs of genes. b Arrangement of OR genes in three genomic clusters. The position of each OR gene is shown by a vertical bar above or below a horizontal line, the latter indicating the opposite transcriptional direction to the former. The phylogenetic clades are defined by the tree in a. A pseudogene is represented by a shorter bar. X indicates an unclassified gene. Modified from Niimura and Nei (2003)

Fig. 3

a Orthologous relationships of OR genes between mouse (Mm) and human (Hs) genomic clusters. Long and short vertical bars show the locations of functional and nonfunctional OR genes respectively. A vertical bar above a horizontal line indicates the opposite transcriptional direction to that below a horizontal line. Different colors represent different phylogenetic clades. Unclassified class II OR genes are shown in black. Red and blue lines connecting mouse and human OR genes represent orthologous gene pairs. Red lines indicate that transcriptional directions of orthologous genes are conserved between mice and humans, whereas blue lines indicate that they are inverted. b Evolutionary changes in the numbers of OR genes in the human lineage (right) and in the mouse lineage (left). Right: it was estimated that 691 functional genes in the most recent common ancestor (MRCA; red) have generated 1,037 functional genes (orange) and 267 pseudogenes out of 354 (green) in mice. The other 87 pseudogenes in mice were estimated to have originated from 63 functional genes in the MRCA (blue). From these numbers, the number of functional genes in the MRCA is estimated to be 754. Left: it was estimated that 326 functional genes in the MRCA (red) have generated 388 functional genes and 193 pseudogenes in humans. Out of the 428 functional genes in the MRCA that were inactivated in the human lineage, 179 genes were estimated to have become 221 pseudogenes. The other 249 genes appear to have been eliminated from the genome. Modified from Niimura and Nei (2005b)

Fig. 4

a Condensed phylogenetic tree (Nei and Kumar 2000) at the 70% bootstrap value level for 310 functional OR genes and two outgroup non-OR G-protein coupled receptor (GPCR) genes (bovine adenosine A1 receptor and rat α2B-adrenergic receptor). This condensed tree was produced from the NJ tree by assuming that all the interior branches showing <70% bootstrap values had a branch length of 0. Note that this tree represents the topology only and the branch lengths do not reflect their evolutionary distances. Gray bars are fish genes from the species other than zebrafish or pufferfish that are available from databases. Black and white dots at nodes indicate the branches supported by >90% and >80% bootstrap values respectively. b Evolutionary dynamics of vertebrate OR genes. The MRCA between jawed and jawless vertebrates and that between fishes and tetrapods were estimated to have had at least two and nine OR genes respectively. Fishes currently retain eight out of nine group genes that were present in the MRCA between fishes and tetrapods, probably because their environment has not changed substantially compared with that of the MRCA. In the tetrapod lineage, group α and γ genes seem to have acquired the ability to detect airborne odorants at the time of terrestrial adaptation. It appears that the importance of olfactory information is greater in terrestrial organisms than in marine organisms, and therefore the OR genes, especially group γ genes, have expanded enormously in the former. In mammals and birds, the genes that are specific to water-soluble odorants have apparently been eliminated from the genome because they are useless for terrestrial life. On the other hand, amphibians still keep the genes for water-soluble odorants, reflecting that they have adapted to both aquatic and terrestrial environments. Modified from Niimura and Nei (2005c)