| Literature DB >> 22559943 |
Megan Y Dennis1, Xander Nuttle, Peter H Sudmant, Francesca Antonacci, Tina A Graves, Mikhail Nefedov, Jill A Rosenfeld, Saba Sajjadian, Maika Malig, Holland Kotkiewicz, Cynthia J Curry, Susan Shafer, Lisa G Shaffer, Pieter J de Jong, Richard K Wilson, Evan E Eichler.
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.Entities:
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Year: 2012 PMID： 22559943 PMCID： PMC3365555 DOI： 10.1016/j.cell.2012.03.033
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582