The Relevance of Genomic Signatures at Adhesion GPCR Loci in Humans.
Adhesion G protein-coupled receptors (aGPCRs) have a long evolutionary history dating back to very basal unicellular eukaryotes. Almost every vertebrate is equipped with a set of different aGPCRs. Genomic sequence data of several hundred extinct and extant species allows for reconstruction of aGPCR phylogeny in vertebrates and non-vertebrates in general but also provides a detailed view into the recent evolutionary history of human aGPCRs. Mining these sequence sources with bioinformatic tools can unveil many facets of formerly unappreciated aGPCR functions. In this review, we extracted such information from the literature and open public sources and provide insights into the history of aGPCR in humans. This includes comprehensive analyses of signatures of selection, variability of human aGPCR genes, and quantitative traits at human aGPCR loci. As indicated by a large number of genome-wide genotype-phenotype association studies, variations in aGPCR contribute to specific human phenotypes. Our survey demonstrates that aGPCRs are significantly involved in adaptation processes, phenotype variations, and diseases in humans.
Integrated Research and Treatment Center (IFB) AdiposityDiseases, Medical Faculty, University of Leipzig, Liebigstr. 21, Leipzig, 04103, Germany. peter.kovacs@medizin.uni-leipzig.de.
Peter
P
Kovacs
Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, Leipzig, 04103, Germany. schoberg@medizin.uni-leipzig.de.
Torsten
T
Schöneberg
D001665:Binding Sites; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D040641:Quantitative Trait Loci; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D059467:Transcriptome
D043562:Receptors, G-Protein-Coupled
Adhesion G protein-coupled receptors; Disease; Genome-wide association studies; Mutation; Natural selection; Population genetics