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Gene. 2006 Jun 21;375:75-9. Epub 2006 Mar 14.

Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ.

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  • 1Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

Abstract

Primary microcephaly is a developmental defect of the brain characterized by severely reduced brain size but an absence of other overt abnormalities. Mutations in several loci have been linked to primary microcephaly. The underlying genes for two of these were recently identified as CDK5RAP2 and CENPJ. Here, we focus on CDK5RAP2 and show that the protein evolutionary rate of this gene is significantly higher in primates than rodents or carnivores. We further show that the evolutionary rate within primates is particularly high in the human and chimpanzee terminal branches. Thus, the pattern of molecular evolution seen in CDK5RAP2 appears to parallel, at least approximately, that seen in two other previously identified primary microcephaly genes, microcephalin and ASPM. We also briefly discuss CENPJ, which similarly exhibits higher rate of protein evolution in primates as compared to rodents and carnivores. Together, the evolutionary patterns of all four presently known primary microcephaly genes are consistent with the hypothesis that genes regulating brain size during development might also play a role in brain evolution in primates and especially humans.

PMID:
16631324
[PubMed - indexed for MEDLINE]
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