The evolution and population diversity of human-specific segmental duplications

Megan Y. 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 Stessman, Xander Nuttle, Kendra Hoekzema, Tina A. Lindsay-Graves, Richard K. Wilson & 1 others Evan E. Eichler

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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
Volume1
Issue number3
DOIs
StatePublished - Feb 17 2017
Externally publishedYes

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gene
genomics
genes
human evolution
hominid
primate
Pongidae
Hominidae
genetic variation
clone
mutation
genome
Primates
protein
clones
proteins
family
analysis

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Ecology

Cite this

Dennis, M. Y., Harshman, L., Nelson, B. J., Penn, O., Cantsilieris, S., Huddleston, J., ... Eichler, E. E. (2017). The evolution and population diversity of human-specific segmental duplications. Nature Ecology and Evolution, 1(3), [0069]. https://doi.org/10.1038/s41559-016-0069

The evolution and population diversity of human-specific segmental duplications. / Dennis, Megan Y.; Harshman, Lana; Nelson, Bradley J.; Penn, Osnat; Cantsilieris, Stuart; Huddleston, John; Antonacci, Francesca; Penewit, Kelsi; Denman, Laura; Raja, Archana; Baker, Carl; Mark, Kenneth; Malig, Maika; Janke, Nicolette; Espinoza, Claudia; Stessman, Holly; Nuttle, Xander; Hoekzema, Kendra; Lindsay-Graves, Tina A.; Wilson, Richard K.; Eichler, Evan E.

In: Nature Ecology and Evolution, Vol. 1, No. 3, 0069, 17.02.2017.

Research output: Contribution to journalArticle

Dennis, MY, Harshman, L, Nelson, BJ, 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, Nuttle, X, Hoekzema, K, Lindsay-Graves, TA, Wilson, RK & Eichler, EE 2017, 'The evolution and population diversity of human-specific segmental duplications', Nature Ecology and Evolution, vol. 1, no. 3, 0069. https://doi.org/10.1038/s41559-016-0069
Dennis MY, Harshman L, Nelson BJ, Penn O, Cantsilieris S, Huddleston J et al. The evolution and population diversity of human-specific segmental duplications. Nature Ecology and Evolution. 2017 Feb 17;1(3). 0069. https://doi.org/10.1038/s41559-016-0069
Dennis, Megan Y. ; Harshman, Lana ; Nelson, Bradley J. ; Penn, Osnat ; Cantsilieris, Stuart ; Huddleston, John ; Antonacci, Francesca ; Penewit, Kelsi ; Denman, Laura ; Raja, Archana ; Baker, Carl ; Mark, Kenneth ; Malig, Maika ; Janke, Nicolette ; Espinoza, Claudia ; Stessman, Holly ; Nuttle, Xander ; Hoekzema, Kendra ; Lindsay-Graves, Tina A. ; Wilson, Richard K. ; Eichler, Evan E. / The evolution and population diversity of human-specific segmental duplications. In: Nature Ecology and Evolution. 2017 ; Vol. 1, No. 3.
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