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The Evolutionary History of Vertebrate Adhesion GPCRs and Its Implication on Their Classification

Adhesion G protein-coupled receptors (aGPCRs) form a structurally separate class of
GPCRs with an unresolved evolutionary history and classification. Based on phylogenetic relations
of human aGPCRs, nine families (A–G, L, V) were distinguished. Taking advantage of available
genome data, we determined the aGPCR repertoires in all vertebrate classes. Although most aGPCR
families show a high numerical stability in vertebrate genomes, the full repertoire of family E, F,
and G members appeared only after the fish–tetrapod split. We did not find any evidence for new
aGPCR families in vertebrates which are not present in the human genome. Based on ortholog
sequence alignments, selection analysis clearly indicated two types of tetrapod aGPCRs: (i) aGPCR
under strong purifying selection in tetrapod evolution (families A, B, D, L, V); and (ii) aGPCR with
signatures of positive selection in some tetrapod linages (families C, E, G, F). The alignments of
aGPCRs also allowed for a revised definition of reference positions within the seven-transmembranehelix
domain (relative position numbering scheme). Based on our phylogenetic cluster analysis, we
suggest a revised nomenclature of aGPCRs including their transcript variants. Herein, the former
families E and L are combined to one family (L) and GPR128/ADGRG7 forms a separate family (E).
Furthermore, our analyses provide valuable information about the (patho)physiological relevance of
individual aGPCR members.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89197
Date23 January 2024
CreatorsWittlake, Aline, Prömel, Simone, Schöneberg, Torsten
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation11803

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