@article{9571ee009e484c0591d39f198f12a662,
title = "Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication",
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.",
author = "Dennis, \{Megan Y.\} and Xander Nuttle and Sudmant, \{Peter H.\} and Francesca Antonacci and Graves, \{Tina A.\} and Mikhail Nefedov and Rosenfeld, \{Jill A.\} and Saba Sajjadian and Maika Malig and Holland Kotkiewicz and Curry, \{Cynthia J.\} and Susan Shafer and Shaffer, \{Lisa G.\} and \{De Jong\}, \{Pieter J.\} and Wilson, \{Richard K.\} and Eichler, \{Evan E.\}",
note = "Funding Information: We thank B. Coe for assistance in CNV analysis and the 1000 Genomes Project for access to sequence data of the SRGAP2 loci. For DNA samples used in paralog-specific CNV screening and detailed phenotypic information of patients, we would like to thank C. Romano, M. Fichera, J. G{\'e}cz, B. de Vries, R. Bernier, the Simons Foundation, Autism Speaks, the National Institute of Mental Health, and the ClinSeq Project. We acknowledge C. Baker, L. Vives, and J. Huddleston for technical assistance, T. Brown for manuscript editing, and the laboratory of S. Fields for use of their Roche LC480. We also thank J. Akey, T. Marques-Bonet, A. Andres, S. Girirajan, and K. Meltz Steinberg for helpful discussion, as well as the laboratory of F. Polleux for comments and kindly sharing human RNA samples for expression studies. The BAC clones from the complete hydatidiform mole were derived from a cell line created by U. Surti. M.Y.D. is supported by U.S. National Institutes of Health (NIH) Ruth L. Kirchstein National Research Service Award (NRSA) Fellowship (1F32HD071698-01). X.N. is supported by an NIH NRSA Genome Training Grant to the University of Washington (2T32HG000035-16). P.H.S. is a Howard Hughes Medical Institute International Student Research Fellow. This work was supported by NIH Grants HG002385 and GM058815. E.E.E. is an investigator of the Howard Hughes Medical Institute. J.A.R. and L.G.S. are employees of Signature Genomic Laboratories, a subsidiary of PerkinElmer, Inc. E.E.E. is on the scientific advisory boards for Pacific Biosciences, Inc. and SynapDx Corp. ",
year = "2012",
month = may,
day = "11",
doi = "10.1016/j.cell.2012.03.033",
language = "English",
volume = "149",
pages = "912--922",
journal = "Cell",
issn = "0092-8674",
number = "4",
}