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

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Dennis, Megan Y; Nuttle, Xander; Sudmant, Peter H; Antonacci, Francesca; Graves, Tina A; Nefedov, Mikhail; Rosenfeld, Jill A; Sajjadian, Saba; Malig, Maika; Kotkiewicz, Holland; Curry, Cynthia J; Shafer, Susan; Shaffer, Lisa G; de Jong, Pieter J; Wilson, Richard K; Eichler, Evan E
Year of Publication: 2012
Journal: Cell
Volume: 149
Issue: 4
Pagination: 912-22
Date Published: 2012 May 11
Publication Language: eng
ISSN: 1097-4172
Keywords: Animals, DNA Copy Number Variations, Evolution, Molecular, Female, Genetics, Medical, GTPase-Activating Proteins, Humans, Hydatidiform Mole, In Situ Hybridization, Fluorescence, Mammals, Molecular Sequence Data, Pregnancy, Primates, Segmental Duplications, Genomic

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.

DOI: 10.1016/j.cell.2012.03.033
Alternate Journal: Cell