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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 May 8

PMID 22559943

Citations 202

Authors

Megan Y 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

Affiliations

Soon will be listed here.

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.

Citing Articles

Structural variation, selection, and diversification of the gene family from the human pangenome.

Dishuck P, Munson K, Lewis A, Dougherty M, Underwood J, Harvey W bioRxiv. 2025; .

PMID: 39975192 PMC: 11838601. DOI: 10.1101/2025.02.04.636496.

Structural polymorphism and diversity of human segmental duplications.

Jeong H, Dishuck P, Yoo D, Harvey W, Munson K, Lewis A Nat Genet. 2025; 57(2):390-401.

PMID: 39779957 PMC: 11821543. DOI: 10.1038/s41588-024-02051-8.

The De Novo Emergence of Two Brain Genes in the Human Lineage Appears to be Unsupported.

Hannon Bozorgmehr J J Mol Evol. 2024; 93(1):3-10.

PMID: 39725692 DOI: 10.1007/s00239-024-10227-3.

Cis-Regulatory Evolution of CCNB1IP1 Driving Gradual Increase of Cortical Size and Folding in primates.

Hu T, Kong Y, Tan Y, Ma P, Wang J, Sun X bioRxiv. 2024; .

PMID: 39713381 PMC: 11661109. DOI: 10.1101/2024.12.08.627376.

Modelling human brain development and disease with organoids.

Birtele M, Lancaster M, Quadrato G Nat Rev Mol Cell Biol. 2024; .

PMID: 39668188 DOI: 10.1038/s41580-024-00804-1.

References

Stedman H, Kozyak B, Nelson A, Thesier D, Su L, Low D . Myosin gene mutation correlates with anatomical changes in the human lineage. Nature. 2004; 428(6981):415-8. DOI: 10.1038/nature02358. View

Antonacci F, Kidd J, Marques-Bonet T, Teague B, Ventura M, Girirajan S . A large and complex structural polymorphism at 16p12.1 underlies microdeletion disease risk. Nat Genet. 2010; 42(9):745-50. PMC: 2930074. DOI: 10.1038/ng.643. View

Kidd J, Cooper G, Donahue W, Hayden H, Sampas N, Graves T . Mapping and sequencing of structural variation from eight human genomes. Nature. 2008; 453(7191):56-64. PMC: 2424287. DOI: 10.1038/nature06862. View

Reich D, Green R, Kircher M, Krause J, Patterson N, Durand E . Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010; 468(7327):1053-60. PMC: 4306417. DOI: 10.1038/nature09710. View

Thompson J, Gibson T, Higgins D . Multiple sequence alignment using ClustalW and ClustalX. Curr Protoc Bioinformatics. 2008; Chapter 2:Unit 2.3. DOI: 10.1002/0471250953.bi0203s00. View

Green R, Krause J, Briggs A, Maricic T, Stenzel U, Kircher M . A draft sequence of the Neandertal genome. Science. 2010; 328(5979):710-722. PMC: 5100745. DOI: 10.1126/science.1188021. View

Wu D, Irwin D, Zhang Y . De novo origin of human protein-coding genes. PLoS Genet. 2011; 7(11):e1002379. PMC: 3213175. DOI: 10.1371/journal.pgen.1002379. View

Kimura M . A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980; 16(2):111-20. DOI: 10.1007/BF01731581. View

Eichler E, Flint J, Gibson G, Kong A, Leal S, Moore J . Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11(6):446-50. PMC: 2942068. DOI: 10.1038/nrg2809. View

10.

Fischbach G, Lord C . The Simons Simplex Collection: a resource for identification of autism genetic risk factors. Neuron. 2010; 68(2):192-5. DOI: 10.1016/j.neuron.2010.10.006. View

11.

Patterson N, Richter D, Gnerre S, Lander E, Reich D . Genetic evidence for complex speciation of humans and chimpanzees. Nature. 2006; 441(7097):1103-8. DOI: 10.1038/nature04789. View

12.

Lynch M, Conery J . The evolutionary fate and consequences of duplicate genes. Science. 2000; 290(5494):1151-5. DOI: 10.1126/science.290.5494.1151. View

13.

Gregory S, Barlow K, McLay K, Kaul R, Swarbreck D, Dunham A . The DNA sequence and biological annotation of human chromosome 1. Nature. 2006; 441(7091):315-21. DOI: 10.1038/nature04727. View

14.

Kajii T, Ohama K . Androgenetic origin of hydatidiform mole. Nature. 1977; 268(5621):633-4. DOI: 10.1038/268633a0. View

15.

Parsons J . Miropeats: graphical DNA sequence comparisons. Comput Appl Biosci. 1995; 11(6):615-9. DOI: 10.1093/bioinformatics/11.6.615. View

16.

Bailey J, Gu Z, Clark R, Reinert K, Samonte R, Schwartz S . Recent segmental duplications in the human genome. Science. 2002; 297(5583):1003-7. DOI: 10.1126/science.1072047. View

17.

Geschwind D, Sowinski J, Lord C, Iversen P, Shestack J, Jones P . The autism genetic resource exchange: a resource for the study of autism and related neuropsychiatric conditions. Am J Hum Genet. 2001; 69(2):463-6. PMC: 1235320. DOI: 10.1086/321292. View

18.

Osoegawa K, Woon P, Zhao B, Frengen E, Tateno M, Catanese J . An improved approach for construction of bacterial artificial chromosome libraries. Genomics. 1998; 52(1):1-8. DOI: 10.1006/geno.1998.5423. View

19.

Saitou N, Nei M . The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4):406-25. DOI: 10.1093/oxfordjournals.molbev.a040454. View

20.

Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L . Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2004; 2(7):E207. PMC: 449870. DOI: 10.1371/journal.pbio.0020207. View