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PMID: 28580430 Published · ppublish English Journal Article

The evolution and population diversity of human-specific segmental duplications.

Nature ecology & evolution ·Vol. 1 ·No. 3 ·2017-00-00 ·Pages 69

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 HAF, Nuttle X, Hoekzema K, Lindsay-Graves TA, Wilson RK, Eichler EE

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/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 (e.g., TCAF1/2), we highlight ten gene families (e.g., 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.

Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Dennis Megan Y
Genome Center, MIND Institute, and Department of Biochemistry & Molecular Medicine, University of California, Davis, CA 95616, USA. | Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Harshman Lana
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Nelson Bradley J
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Penn Osnat
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Cantsilieris Stuart
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Huddleston John
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. | Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Antonacci Francesca
Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro", Bari 70125, Italy.
Penewit Kelsi
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Denman Laura
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Raja Archana
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. | Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Baker Carl
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Mark Kenneth
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Malig Maika
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Janke Nicolette
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Espinoza Claudia
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Stessman Holly A F
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Nuttle Xander
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Hoekzema Kendra
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Lindsay-Graves Tina A
McDonnell Genome Institute at Washington University, Washington University School of Medicine, St. Louis, MO 63108, USA.
Wilson Richard K
McDonnell Genome Institute at Washington University, Washington University School of Medicine, St. Louis, MO 63108, USA.
Eichler Evan E
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. | Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Conflict of Interest

COMPETING FINANCIAL INTERESTS E.E.E. is on the scientific advisory board (SAB) of DNAnexus, Inc., is a consultant for Kunming University of Science and Technology (KUST) as part of the 1000 China Talent Program, and was an SAB member of Pacific Biosciences, Inc. (2009–2013).

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Article Info
Journal
Nature ecology & evolution
Abbr.
Nat Ecol Evol
ISSN
2397-334X
DOI
10.1038/s41559-016-0069
Published
2017-00-00
Epub
2017-00-17
Pages
69
Language
English
Region
England
NLM ID
101698577
PMCID
PMC5450946
Grants
NICHD NIH HHS · T32 HD007396 · United States
NINDS NIH HHS · R00 NS083627 · United States
NHGRI NIH HHS · U41 HG007635 · United States
NICHD NIH HHS · U54 HD079125 · United States
Howard Hughes Medical Institute · United States
NHGRI NIH HHS · R25 HG007153 · United States
NHGRI NIH HHS · R01 HG002385 · United States
NIMH NIH HHS · R01 MH101221 · United States
External Links
PubMed source DOI: 10.1038/s41559-016-0069 PMC Full Text View journal details
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