The evolution and population diversity of human-specific segmental duplications

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

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.

Journal: Nature ecology & evolution
DOI: 10.1038/s41559-016-0069
Year: 2017

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