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Primate genome architecture influences structural variation mechanisms and functional consequences
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Primate genome architecture influences structural variation mechanisms and functional consequences

  1. Jan O. Korbelc,i,4,5
  1. aDepartment of Pathology, Brigham and Women’s Hospital, Boston, MA 02115;
  2. bHarvard Medical School, Boston, MA 02115;
  3. cEuropean Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany;
  4. dDivision of Genetics, Brigham and Women's Hospital, Boston, MA 02115;
  5. eScientific Computing Group, Heidelberg Institute for Theoretical Studies (HITS), 69117 Heidelberg, Germany;
  6. fEuropean Molecular Biology Laboratory, Genomics Core Facility, 69117 Heidelberg, Germany;
  7. gDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48103;
  8. hSeoul National University College of Medicine, Seoul 110-799, South Korea; and
  9. iEuropean Molecular Biology Laboratory—European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, United Kingdom
  1. Edited* by J. G. Seidman, Harvard Medical School, Boston, MA, and approved July 24, 2013 (received for review March 30, 2013)


Genomic structural variants (SVs) significantly contribute to human genetic variation and have been linked with numerous diseases. Compared with humans, the characterization of SVs occurring within and across nonhuman primates has lagged. We generated comprehensive massively parallel DNA sequencing-based SV maps in three nonhuman primate species and show that the rates of different SV formation mechanisms, such as nonallelic homologous recombination and Alu retrotransposition, vary significantly between the great apes and the rhesus macaque—leading to markedly different SV landscapes in these species. Linking gene expression data with species-specific gene duplications, we describe several instances where gene duplicates seem to lead to evolutionary innovation through the gain of gene expression in new tissues.


Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes. By comparison, nonallelic homologous recombination is specifically active in the great apes, which is correlated with architectural differences between the genomes of great apes and macaque. Transcriptome analyses across nonhuman primates and humans revealed effects of species-specific whole-gene duplication on gene expression. We identified 13 gene duplications coinciding with the species-specific gain of tissue-specific gene expression in keeping with a role of gene duplication in the promotion of diversification and the acquisition of unique functions. Differences in the present day activity of SV formation mechanisms that our study revealed may contribute to ongoing diversification and adaptation of great ape and Old World monkey lineages.


  • 1Present address: Department of Biological Sciences, State University of New York, Buffalo, NY 14260.

  • 2O.G. and V.T. contributed equally to this work.

  • 3Present address: Jackson Laboratory Institute for Genomic Medicine, Farmington, CT 06030.

  • 4C.L. and J.O.K. contributed equally to this work.

  • 5To whom correspondence may be addressed. E-mail: charles.lee{at} or jan.korbel{at}
  • Author contributions: O.G., V.T., C.L., and J.O.K. designed research; O.G., V.T., J.T., Q.Z., R.C.I., A.L., A.M.S., and V.B. performed research; E.L., M.H.-Y.F., V.B., P.J.P., and C.L. contributed new reagents/analytic tools; O.G., V.T., J.T., Q.Z., R.C.I., E.L., M.H.-Y.F., P.P., R.E.M., and J.O.K. analyzed data; and O.G., V.T., C.L., and J.O.K. wrote the paper.

  • The authors declare no conflict of interest.

  • *This Direct Submission article had a prearranged editor.

  • Data deposition: The sequencing and aCGH data reported in this paper have been deposited in the European Nucleotide Archive, (accession no. ERP002376) and the Gene Expression Omnibus (GEO) database, (accession no. GSE45741), respectively. In addition, all the callsets are available at

  • This article contains supporting information online at

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