Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication

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• 作者：Megan  ; Y. Dennis¹ ; ⁸ ; Xander Nuttle¹ ; ⁸ ; Peter  ; H. Sudmant¹ ; Francesca Antonacci¹ ; Tina  ; A. Graves³ ; Mikhail Nefedov⁴ ; Jill  ; A. Rosenfeld⁵ ; Saba Sajjadian¹ ; Maika Malig¹ ; Holland Kotkiewicz³ ; Cynthia  ; J. Curry⁶ ; Susan Shafer⁷ ; Lisa  ; G. Shaffer⁵ ; Pieter  ; J. de  ; Jong⁴ ; Richard  ; K. Wilson³ ; Evan  ; E. Eichler¹ ; ² ; ^{eee@gs.washington.edu}
• 刊名：Cell
• 出版年：2012
• 期刊代码：50_00928674
• 类别：med
• 出版时间：11 May, 2012
• 卷：149
• 期：4
• 页码：912-922
• 文件大小：895 K

摘要

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Summary

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) 鈭?.4 million years ago (mya). Two larger duplications later copied SRGAP2B to chromosome 1p12 (SRGAP2C) and to proximal 1q21.1 (SRGAP2D) 鈭?.4 and 鈭? mya, respectively. Sequence and expression analyses show that SRGAP2C is the most likely duplicate to encode聽a functional protein and is among the most fixed human-specific duplicate genes. Our data suggest聽a mechanism where incomplete duplication created聽a novel gene function鈥攁ntagonizing parental SRGAP2 function鈥攊mmediately 鈥渁t birth鈥?2-3 mya, which is聽a time corresponding to the transition from Australopithecus to Homo and the beginning of neocortex expansion.