The evolution and population diversity of human-specific segmental duplications

Megan Dennis, Lana Harshman, Bradley J. Nelson, Osnat Penn, Stuart Cantsilieris, John Huddleston, Francesca Antonacci, Kelsi Penewit, Laura Denman, Archana Raja, Carl Baker, Kenneth Mark, Maika Malig, Nicolette Janke, Claudia Espinoza, Holly A.F. Stessman, Xander Nuttle, Kendra Hoekzema, Tina A. Lindsay-Graves, Richard K. WilsonEvan E. Eichler

Research output: Contribution to journalArticle

42 Scopus citations


Segmental duplications contribute to human evolution, adaptation and genomic instability but are often poorly characterized. We investigate the evolution, genetic variation and coding potential of human-specific segmental duplications (HSDs). We identify 218 HSDs based on analysis of 322 deeply sequenced archaic and contemporary hominid genomes. We sequence 550 human and nonhuman primate genomic clones to reconstruct the evolution of the largest, most complex regions with protein-coding potential (N = 80 genes from 33 gene families). We show that HSDs are non-randomly organized, associate preferentially with ancestral ape duplications termed 'core duplicons' and evolved primarily in an interspersed inverted orientation. In addition to Homo sapiens-specific gene expansions (such as TCAF1/TCAF2), we highlight ten gene families (for example, ARHGAP11B and SRGAP2C) where copy number never returns to the ancestral state, there is evidence of mRNA splicing and no common gene-disruptive mutations are observed in the general population. Such duplicates are candidates for the evolution of human-specific adaptive traits.

Original languageEnglish (US)
Article number0069
JournalNature Ecology and Evolution
Issue number3
StatePublished - Feb 17 2017

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology

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    Dennis, M., Harshman, L., Nelson, B. J., Penn, O., Cantsilieris, S., Huddleston, J., Antonacci, F., Penewit, K., Denman, L., Raja, A., Baker, C., Mark, K., Malig, M., Janke, N., Espinoza, C., Stessman, H. A. F., Nuttle, X., Hoekzema, K., Lindsay-Graves, T. A., ... Eichler, E. E. (2017). The evolution and population diversity of human-specific segmental duplications. Nature Ecology and Evolution, 1(3), [0069].