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. 2010 Jan;3(1):52-63.
doi: 10.1111/j.1752-4571.2009.00098.x. Epub 2009 Sep 7.

Evolutionary genomics of human intellectual disability

Bernard Crespi  1 , Kyle Summers  2 , Steve Dorus  3
Affiliations

Evolutionary genomics of human intellectual disability

Bernard Crespi et al. Evol Appl. 2010 Jan.

Abstract

Previous studies have postulated that X-linked and autosomal genes underlying human intellectual disability may have also mediated the evolution of human cognition. We have conducted the first comprehensive assessment of the extent and patterns of positive Darwinian selection on intellectual disability genes in humans. We report three main findings. First, as noted in some previous reports, intellectual disability genes with primary functions in the central nervous system exhibit a significant concentration to the X chromosome. Second, there was no evidence for a higher incidence of recent positive selection on X-linked than autosomal intellectual disability genes, nor was there a higher incidence of selection on such genes overall, compared to sets of control genes. However, the X-linked intellectual disability genes inferred to be subject to recent positive selection were concentrated in the Rho GTP-ase pathway, a key signaling pathway in neural development and function. Third, among all intellectual disability genes, there was evidence for a higher incidence of recent positive selection on genes involved in DNA repair, but not for genes involved in other functions. These results provide evidence that alterations to genes in the Rho GTP-ase and DNA-repair pathways may play especially-important roles in the evolution of human cognition and vulnerability to genetically-based intellectual disability.

Keywords: genetic; genomic; intellectual disability; positive selection.

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References

    1. Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, et al. Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Human Mutation. 2003;22:442–450. - PubMed
    1. Arden R, Plomin R. Sex differences in variance of intelligence across childhood. Personality and Individual Differences. 2006;41:39–48.
    1. Balajee AS. DNA Repair and Human Disease. New York, NY: Springer Science; 2006.
    1. Belmonte MK, Bourgeron T. Fragile X syndrome and autism at the intersection of genetic and neural networks. Nature Neuroscience. 2006;9:1221–1225. - PubMed
    1. Billuart P, Chelly J. From fragile X mental retardation protein to Rac1 GTPase: new insights from Fly CYFIP. Neuron. 2003;38:843–845. - PubMed

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