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 | |
| State | Published - May 11 2012 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
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
}
TY - JOUR
T1 - Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication
AU - Dennis, Megan
AU - Nuttle, Xander
AU - Sudmant, Peter H.
AU - Antonacci, Francesca
AU - Graves, Tina A.
AU - Nefedov, Mikhail
AU - Rosenfeld, Jill A.
AU - Sajjadian, Saba
AU - Malig, Maika
AU - Kotkiewicz, Holland
AU - Curry, Cynthia J.
AU - Shafer, Susan
AU - Shaffer, Lisa G.
AU - De Jong, Pieter J.
AU - Wilson, Richard K.
AU - Eichler, Evan E.
PY - 2012/5/11
Y1 - 2012/5/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860860685&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860860685&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.03.033
DO - 10.1016/j.cell.2012.03.033
M3 - Article
C2 - 22559943
AN - SCOPUS:84860860685
VL - 149
SP - 912
EP - 922
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -