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1 Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
2 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
3 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, USA

The common seven-transmembranedomain (TMD) architecture of G proteincoupled receptors (GPCRs) has been preserved over a vast period of time, and highly conserved amino acid motifs and residues have evolved to establish ligand and signal transduction specificities. The mining of evolutionary data from sequenced genomes and targeted retrieved orthologs has proven helpful for understanding the physiological relevance of individual GPCRs and for interpreting the clinical significance of GPCR mutations in structural terms. Sequence analysis of GPCR pseudogenes, which are considered as genomic traces of past functions, as well as recent success in sequence analysis of GPCR genes from extinct species, provide further information. This review discusses recent advances and approaches aimed at developing a better understanding of GPCR biology based on evolutionary data.
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