Evolution of Trace Amine–Associated Receptor (TAAR) Gene Family in Vertebrates: Lineage-Specific Expansions and Degradations of a Second Class of Vertebrate Chemosensory Receptors Expressed in the Olfactory Epithelium

Abstract

The trace amine-associated receptors (TAARs) form a specific family of G protein-coupled receptors in vertebrates. TAARs were initially considered neurotransmitter receptors, but recent study showed that mouse TAARs function as chemosensory receptors in the olfactory epithelium. To clarify the evolutionary dynamics of the TAAR gene family in vertebrates, near-complete repertoires of TAAR genes and pseudogenes were identified from the genomic assemblies of 4 teleost fishes (zebrafish, fugu, stickleback, and medaka), western clawed frogs, chickens, 3 mammals (humans, mice, and opossum), and sea lampreys. Database searches revealed that fishes had many putatively functional TAAR genes (13-109 genes), whereas relatively small numbers of TAAR genes (3-22 genes) were identified in tetrapods. Phylogenetic analysis of these genes indicated that the TAAR gene family was subdivided into 5 subfamilies that diverged before the divergence of ray-finned fishes and tetrapods. In tetrapods, virtually all TAAR genes were located in 1 specific region of their genomes as a gene cluster; however, in fishes, TAAR genes were scattered throughout more than 2 genomic locations. This possibly reflects a whole-genome duplication that occurred in the common ancestor of ray-finned fishes. Expression analysis of zebrafish and stickleback TAAR genes revealed that many TAARs in these fishes were expressed in the olfactory organ, suggesting the relatively high importance of TAARs as chemosensory receptors in fishes. A possible evolutionary history of the vertebrate TAAR gene family was inferred from the phylogenetic and comparative genomic analyses.

Evolution of GPCR: Change and continuity

“…As simultaneous pseudogenization in different species due to neutral drift is very unlikely, a common selection process like a rodent-hominoid-specific pathogen was speculated [81]. A similar situation was found in TAAR that possibly function as chemosensory receptors in olfactory epithelia [74,126]. Two paralogs of this family, TAAR3 and TAAR4 independently became pseudogenized in great apes and New World monkeys on a comparable time scale on different continents (Stäubert/Schöneberg unpublished data).…”

“…Indeed, conserved synteny indicates that chromosomal duplication generated a set of paralogous genes on chromosomes 4 and 5 including the dopamine and adrenergic receptor paralogs, DRD5 and DRD1 and ADRA2C and ADRA1, respectively [67]. M a n u s c r i p t -6 -A number of GPCR subfamilies that were subject to independent rapid yet species-specific expansion, including olfactory [68][69][70], chemokine [71], aminergic [72], trace amineassociated (TAAR) [73,74], vomeronasal [75] and nucleotide receptor-like receptors [76], occur in clusters within the vertebral genomes and are often arranged in a tandem fashion. This implies a duplication mechanism that is confined to a genomic region.…”

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

“…While all TAAR sequences do cluster together, the relationships among TAAR subtypes are highly dynamic, reflecting the extensive expansion and contraction events characterizing this receptor family's evolution (Lindemann et al, 2005;Hashiguchi and Nishida, 2007;Stäubert et al, 2010Stäubert et al, , 2013. In fact, the TAAR subtree, displayed in Figure 5, differs somewhat from previously proposed TAAR phylogenies (Lindemann et al, 2005;Hashiguchi and Nishida, 2007). In particular, the presence of several lineage-specific subclades as well as unresolved subclades generate novel hypotheses regarding TAAR subtype origins.…”

“…In spite of these receptors' biological and clinical importance, studies on their evolution are limited and have predomi-nantly focused on individual receptor subtypes, namely TAAR (Gloriam et al, 2005;Lindemann et al, 2005;Hashiguchi and Nishida, 2007), DRD (Callier et al, 2003;Yamamoto et al, 2013), and 5HTR (Anbazhagan et al, 2010). Moreover, many of these studies, and indeed studies on the general evolution of the Rhodopsin-like family, have examined very narrow species distributions, for instance specifically teleosts (Gloriam et al, 2005), primates (Anbazhagan et al, 2010), humans and mice (Vassilatis et al, 2003;Kakarala and Jamil, 2014), or even strictly humans (Fredriksson et al, 2003).…”

From the Olfactory Bulb to Higher Brain Centers: Genetic Visualization of Secondary Olfactory Pathways in Zebrafish

“…It remains unknown what kinds of odorants activate and which types of OSNs innervate the mG cluster, to which the majority of lhx2a tgϩ MCs and a subset of tbr2a tgϩ MCs are apposed. Zebrafish has two other families of olfactory receptors: six V1R-type receptors (also known as ORAs) (Saraiva and Korsching, 2007) and ϳ100 trace amine-associated receptors (TAARs) (Hashiguchi and Nishida, 2007). In addition, teleost fishes including zebrafish have the third type of OSNs, called crypt cells, with unknown functions (Hansen and Zeiske, 1998).…”