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

Megan Dennis; 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

doi:10.1016/j.cell.2012.03.033

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

Megan Dennis, 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

Research output: Contribution to journal › Article › peer-review

208 Scopus citations

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.

Original language	English (US)
Pages (from-to)	912-922
Number of pages	11
Journal	Cell
Volume	149
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2012.03.033
State	Published - May 11 2012
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Dennis, M., Nuttle, X., Sudmant, P. H., Antonacci, F., Graves, T. A., Nefedov, M., Rosenfeld, J. A., Sajjadian, S., Malig, M., Kotkiewicz, H., Curry, C. J., Shafer, S., Shaffer, L. G., De Jong, P. J., Wilson, R. K., & Eichler, E. E. (2012). Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell, 149(4), 912-922. https://doi.org/10.1016/j.cell.2012.03.033

Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. / Dennis, Megan; 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.

In: Cell, Vol. 149, No. 4, 11.05.2012, p. 912-922.

Research output: Contribution to journal › Article › peer-review

Dennis, M, Nuttle, X, Sudmant, PH, Antonacci, F, Graves, TA, Nefedov, M, Rosenfeld, JA, Sajjadian, S, Malig, M, Kotkiewicz, H, Curry, CJ, Shafer, S, Shaffer, LG, De Jong, PJ, Wilson, RK & Eichler, EE 2012, 'Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication', Cell, vol. 149, no. 4, pp. 912-922. https://doi.org/10.1016/j.cell.2012.03.033

Dennis, Megan ; 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. / Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. In: Cell. 2012 ; Vol. 149, No. 4. pp. 912-922.

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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.",

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