Adaptive evolution of genes underlying schizophrenia

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dc.contributor.authorCrespi, Bernarden_US
dc.contributor.authorSummers, Kyleen_US
dc.contributor.authorDorus, Steveen_US
dc.date.accessioned2011-02-17T15:05:47Zen_US
dc.date.accessioned2011-05-17T14:35:26Z
dc.date.available2011-02-17T15:05:47Zen_US
dc.date.available2011-05-17T14:35:26Z
dc.date.issued2007-11-22en_US
dc.description.abstractSchizophrenia poses an evolutionary-genetic paradox because it exhibits strongly negative fitness effects and high heritability, yet it persists at a prevalence of approximately 1% across all human cultures. Recent theory has proposed a resolution: that genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits. This hypothesis predicts that genes increasing the risk of this disorder have been subject to positive selection in the evolutionary history of humans and other primates. We evaluated this prediction using tests for recent selective sweeps in human populations and maximum-likelihood tests for selection during primate evolution. Significant evidence for positive selection was evident using one or both methods for 28 of 76 genes demonstrated to mediate liability to schizophrenia, including DISC1, DTNBP1 and NRG1, which exhibit especially strong and well-replicated functional and genetic links to this disorder. Strong evidence of non-neutral, accelerated evolution was found for DISC1, particularly for exon 2, the only coding region within the schizophrenia-associated haplotype. Additionally, genes associated with schizophrenia exhibited a statistically significant enrichment in their signals of positive selection in HapMap and PAML analyses of evolution along the human lineage, when compared with a control set of genes involved in neuronal activities. The selective forces underlying adaptive evolution of these genes remain largely unknown, but these findings provide convergent evidence consistent with the hypothesis that schizophrenia represents, in part, a maladaptive by-product of adaptive changes during human evolution. Originally published Proceedings of the Royal Society B, Vol. 274, No. 1627, Nov 2007en_US
dc.identifier.citationProceedings of the Royal Society B; 274:1627 p. 2801-2810en_US
dc.identifier.doi10.1098/rspb.2007.0876
dc.identifier.pmidPMC2288689en_US
dc.identifier.urihttp://hdl.handle.net/10342/3226en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://rspb.royalsocietypublishing.org/content/274/1627/2801en_US
dc.rightsAuthor notified of opt-out rights by Cammie Jennings prior to upload of this article.en_US
dc.subjectAdaptive evolutionen_US
dc.subjectSchizophreniaen_US
dc.subjectPositive Darwinian selectionen_US
dc.subjectDisease geneticsen_US
dc.titleAdaptive evolution of genes underlying schizophreniaen_US
dc.typeArticleen_US
ecu.journal.issue1627
ecu.journal.nameProceedings of the Royal Society B
ecu.journal.pages2801-2810
ecu.journal.volume274

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