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

Cell. 2012 May 11;149(4):912-22. doi: 10.1016/j.cell.2012.03.033. Epub 2012 May 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Copy Number Variations
  • Evolution, Molecular*
  • Female
  • GTPase-Activating Proteins / genetics*
  • Genetics, Medical
  • Humans
  • Hydatidiform Mole / genetics
  • In Situ Hybridization, Fluorescence
  • Mammals / genetics
  • Molecular Sequence Data
  • Pregnancy
  • Primates / genetics*
  • Segmental Duplications, Genomic*


  • GTPase-Activating Proteins
  • SRGAP2 protein, human

Associated data

  • GENBANK/AC240103
  • GENBANK/AC241377
  • GENBANK/AC241585
  • GENBANK/AC242498
  • GENBANK/AC243754
  • GENBANK/AC243994
  • GENBANK/AC244015
  • GENBANK/AC244016
  • GENBANK/AC244017
  • GENBANK/AC244018
  • GENBANK/AC244019
  • GENBANK/AC244020
  • GENBANK/AC244021
  • GENBANK/AC244023
  • GENBANK/AC244024
  • GENBANK/AC244034
  • GENBANK/AC244035
  • GENBANK/AC244158
  • GENBANK/AC244159
  • GENBANK/AC244453
  • GENBANK/FP700108
  • GENBANK/FP700111