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Cell. 2012 May 11;149(4):912-22. doi: 10.1016/j.cell.2012.03.033. Epub 2012 May 3.

Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication.

Author information

1
Department of Genome Sciences, University of Washington School of Medicine, Seattle, 98195, USA.

Abstract

Gene duplication is an important source of phenotypic change and adaptive evolution. We leverage a haploid hydatidiform mole to identify highly identical sequences missing from the reference genome, confirming that the cortical development gene Slit-Robo Rho GTPase-activating protein 2 (SRGAP2) duplicated three times exclusively in humans. We show that the promoter and first nine exons of SRGAP2 duplicated from 1q32.1 (SRGAP2A) to 1q21.1 (SRGAP2B) ∼3.4 million years ago (mya). Two larger duplications later copied SRGAP2B to chromosome 1p12 (SRGAP2C) and to proximal 1q21.1 (SRGAP2D) ∼2.4 and ∼1 mya, respectively. Sequence and expression analyses show that SRGAP2C is the most likely duplicate to encode a functional protein and is among the most fixed human-specific duplicate genes. Our data suggest a mechanism where incomplete duplication created a novel gene function-antagonizing parental SRGAP2 function-immediately "at birth" 2-3 mya, which is a time corresponding to the transition from Australopithecus to Homo and the beginning of neocortex expansion.

PMID:
22559943
PMCID:
PMC3365555
DOI:
10.1016/j.cell.2012.03.033
[Indexed for MEDLINE]
Free PMC Article

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