title: Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception.
abstract: MRGX2, a G-protein-coupled receptor, is specifically expressed in the sensory neurons of the human peripheral nervous system and involved in nociception. Here, we studied DNA polymorphism patterns and evolution of the MRGX2 gene in world-wide human populations and the representative nonhuman primate species. Our results demonstrated that MRGX2 had undergone adaptive changes in the path of human evolution, which were likely caused by Darwinian positive selection. The patterns of DNA sequence polymorphisms in human populations showed an excess of derived substitutions, which against the expectation of neutral evolution, implying that the adaptive evolution of MRGX2 in humans was a relatively recent event. The reconstructed secondary structure of the human MRGX2 revealed that three of the four human-specific amino acid substitutions were located in the extra-cellular domains. Such critical substitutions may alter the interactions between MRGX2 protein and its ligand, thus, potentially led to adaptive changes of the pain-perception-related nervous system during human evolution.
authors.affiliation: Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Alice A
authors.initials: AA
authors.lastname: Lin
authors.forename: L Luca
authors.initials: LL
authors.lastname: Cavalli-Sforza
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Su
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000235:genetics; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C480039:MRGPRX2 protein, human; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D004247:DNA