Selection on the regulation of sympathetic nervous activity in humans and chimpanzees

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dc.contributor.authorLee, Kang Seonko
dc.contributor.authorChatterjee, Paramitako
dc.contributor.authorChoi, Eun-Youngko
dc.contributor.authorSung, Min Kyungko
dc.contributor.authorOh, Jaehoko
dc.contributor.authorWon, Hyejungko
dc.contributor.authorPark, Seong-Minko
dc.contributor.authorKim, Youn-Jaeko
dc.contributor.authorYi, Soojin V.ko
dc.contributor.authorChoi, Jung Kyoonko
dc.date.accessioned2018-05-24T02:43:44Z-
dc.date.available2018-05-24T02:43:44Z-
dc.date.created2018-05-21-
dc.date.created2018-05-21-
dc.date.created2018-05-21-
dc.date.created2018-05-21-
dc.date.issued2018-04-
dc.identifier.citationPLOS GENETICS, v.14, no.4-
dc.identifier.issn1553-7404-
dc.identifier.urihttp://hdl.handle.net/10203/242355-
dc.description.abstractAdrenergic alpha C-2 receptor (ADRA2C) is an inhibitory modulator of the sympathetic nervous system. Knockout mice for this gene show physiological and behavioural alterations that are associated with the fight-or-flight response. There is evidence of positive selection on the regulation of this gene during chicken domestication. Here, we find that the neuronal expression of ADRA2C is lower in human and chimpanzee than in other primates. On the basis of three-dimensional chromatin structure, we identified a cis-regulatory region whose DNA sequences have been significantly accelerated in human and chimpanzee. Active histone modification marks this region in rhesus macaque but not in human and chimpanzee; instead, repressive marks are enriched in various human brain samples. This region contains two neuron-restrictive silencer factor (NRSF) binding motifs, each of which harbours a polymorphism. Our genotyping and analysis of population genome data indicate that at both polymorphic sites, the derived allele has reached fixation in humans and chimpanzees but not in bonobos, whereas only the ancestral allele is present among macaques. Our CRISPR/Cas9 genome editing and reporter assays show that both derived nucleotides repress ADRA2C, most likely by increasing NRSF binding. In addition, we detected signatures of recent positive selection for lower neuronal ADRA2C expression in humans. Our findings indicate that there has been selective pressure for enhanced sympathetic nervous activity in the evolution of humans and chimpanzees.-
dc.languageEnglish-
dc.publisherPUBLIC LIBRARY SCIENCE-
dc.subjectFACTOR-BINDING PROFILES-
dc.subjectOPEN-ACCESS DATABASE-
dc.subjectPOSITIVE SELECTION-
dc.subjectHUMAN GENOME-
dc.subjectNONCODING SEQUENCES-
dc.subjectNATURAL-SELECTION-
dc.subjectGENETIC-VARIATION-
dc.subjectCHROMATIN STATE-
dc.subjectHUMAN BRAIN-
dc.subjectEVOLUTION-
dc.titleSelection on the regulation of sympathetic nervous activity in humans and chimpanzees-
dc.typeArticle-
dc.identifier.wosid000431115700022-
dc.identifier.scopusid2-s2.0-85046418343-
dc.type.rimsART-
dc.citation.volume14-
dc.citation.issue4-
dc.citation.publicationnamePLOS GENETICS-
dc.identifier.doi10.1371/journal.pgen.1007311-
dc.contributor.localauthorChoi, Jung Kyoon-
dc.contributor.nonIdAuthorChatterjee, Paramita-
dc.contributor.nonIdAuthorChoi, Eun-Young-
dc.contributor.nonIdAuthorWon, Hyejung-
dc.contributor.nonIdAuthorPark, Seong-Min-
dc.contributor.nonIdAuthorKim, Youn-Jae-
dc.contributor.nonIdAuthorYi, Soojin V.-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusFACTOR-BINDING PROFILES-
dc.subject.keywordPlusOPEN-ACCESS DATABASE-
dc.subject.keywordPlusPOSITIVE SELECTION-
dc.subject.keywordPlusHUMAN GENOME-
dc.subject.keywordPlusNONCODING SEQUENCES-
dc.subject.keywordPlusNATURAL-SELECTION-
dc.subject.keywordPlusGENETIC-VARIATION-
dc.subject.keywordPlusCHROMATIN STATE-
dc.subject.keywordPlusHUMAN BRAIN-
dc.subject.keywordPlusEVOLUTION-
dc.subject.keywordPlusFACTOR-BINDING PROFILES-
dc.subject.keywordPlusOPEN-ACCESS DATABASE-
dc.subject.keywordPlusPOSITIVE SELECTION-
dc.subject.keywordPlusHUMAN GENOME-
dc.subject.keywordPlusNONCODING SEQUENCES-
dc.subject.keywordPlusNATURAL-SELECTION-
dc.subject.keywordPlusGENETIC-VARIATION-
dc.subject.keywordPlusCHROMATIN STATE-
dc.subject.keywordPlusHUMAN BRAIN-
dc.subject.keywordPlusEVOLUTION-
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