|Title||Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Dennis, Y, Nuttle, X, Sudmant, H, Antonacci, F, Graves, A, Nefedov, M, Rosenfeld, A, Sajjadian, S, Malig, M, Kotkiewicz, H, Curry, J, Shafer, S, Shaffer, G, Jong, J, Wilson, K, Eichler, E|
|Keywords||brain, brain development, brain function, development, gene duplication|
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.
Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication
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