Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs

Eric J Vallender,Gregory M Miller,Susan V Westmoreland,Zhihua Xie

doi:10.1186/1471-2148-10-51

Eric J Vallender, Gregory M Miller + Show 2 more

Open Access

https://doi.org/10.1186/1471-2148-10-51

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Abstract

BackgroundThe trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land. Trace amine associated receptor 1 (TAAR1) is a wide spectrum aminergic receptor that acts as a modulator in brain monoaminergic systems. Other trace amine associated receptors appear to relate to environmental perception and show a birth-and-death pattern in mammals similar to olfactory receptors.ResultsAcross mammals, avians, and amphibians, the TAAR1 gene is intact and appears to be under strong purifying selection based on rates of amino acid fixation compared to neutral mutations. We have found that in dogs it has become a pseudogene. Our analyses using a comparative genetics approach revealed that the pseudogenization event predated the emergence of the Canini tribe rather than being coincident with canine domestication. By assessing the effects of the TAAR1 agonist β-phenylethylamine on [3H]dopamine uptake in canine striatal synaptosomes and comparing the degree and pattern of uptake inhibition to that seen in other mammals, including TAAR1 knockout mice, wild type mice and rhesus monkey, we found that the TAAR1 pseudogenization event resulted in an uncompensated loss of function.ConclusionThe gene family has seen expansions among certain mammals, notably rodents, and reductions in others, including primates. By placing the trace amine associated receptors in an evolutionary context we can better understand their function and their potential associations with behavior and neurological disease.

Highlights

The trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land
The most widely studied of these receptors is Trace amine associated receptor 1 (TAAR1), which has been shown to bind a wide spectrum of biogenic amines and psychoactive compounds [2,3] (Additional file 1) and is a known modulator of monoaminergic activity [4]
Expression overlaps with regions important in brain monoaminergic function and co-expression of TAAR1 and the dopamine transporter (DAT) has been observed in dopaminergic neurons [8]

Summary

Introduction

The trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land. Trace amine associated receptor 1 (TAAR1) is a wide spectrum aminergic receptor that acts as a modulator in brain monoaminergic systems. Trace amine associated receptors (TAARs) are a family of G-protein coupled receptors that originated prior to the emergence of jawed vertebrates [1]. Studies replacing TAAR1 with LacZ in knock-out mice support these findings with the staining of brain sections in these mice displaying LacZ expression throughout dopaminergic and serotonergic regions [9]. These findings, coupled with a dysregulation of trace amines in psychiatric disease [10], have made understanding the function of this gene relevant

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