Abstract
We conduct a cartography of rhodopsin-like non-olfactory G protein-coupled receptors in the Ensembl database. The most recent genomic data (releases 90–92, 90 vertebrate genomes) are analyzed through the online interface and receptors mapped on phylogenetic guide trees that were constructed based on a set of ~14.000 amino acid sequences. This snapshot of genomic data suggest vertebrate genomes to harbour 142 clades of GPCRs without human orthologues. Among those, 69 have not to our knowledge been mentioned or studied previously in the literature, of which 28 are distant from existing receptors and likely new orphans. These newly identified receptors are candidates for more focused evolutionary studies such as chromosomal mapping as well for in-depth pharmacological characterization. Interestingly, we also show that 37 of the 72 human orphan (or recently deorphanized) receptors included in this study cluster into nineteen closely related groups, which implies that there are less ligands to be identified than previously anticipated. Altogether, this work has significant implications when discussing nomenclature issues for GPCRs.
Highlights
G protein-coupled receptors (GPCRs) are signalling proteins activated by for example neurotransmitters and neuromodulators and as such are involved in many physiological processes
GPCRs have been divided into five main families based on phylogenetic analyses[11,12,13]
The apparition of genomics in the 2000’s has brought an explosion in the amount of discovered GPCRs, yet GPCRs are in most cases named according to their human orthologues[26,36,37,38]
Summary
As consequence of the origin of vertebrate GPCRs through the 2R/3R, in an ideal scenario, for each ancestral receptor we expect four/eight paralogues (that can be referred to as “ohnologues”[16], many ohnologues are equivalent to subtypes). The apparition of genomics in the 2000’s has brought an explosion in the amount of discovered GPCRs, yet GPCRs are in most cases named according to their human orthologues[26,36,37,38] This leads to complex nomenclature issues especially when new clades without human orthologues are identified[39,40,41]. The only way to date to tackle the issue of GPCRs in non-vertebrate species is the tedious manual annotation based on phylogenetic information. Ensembl gene trees are based on a consensus of five tree reconstruction methods: a maximum likelihood based on two types of distances and a neighbor-joining tree based on three types of distances This annotation is a first step towards an experimental classification that would include cloning, pharmacological characterization, as well as a chromosomal analysis
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