Zev N. Kronenberg, Ian T. Fiddes, David Gordon, Shwetha Murali, Stuart Cantsilieris, Olivia S. Meyerson, Jason G. Underwood, Bradley J. Nelson, Mark J. P. Chaisson, Max L. Dougherty, Katherine M. Munson, Alex R. Hastie, Mark Diekhans, Fereydoun Hormozdiari, Nicola Lorusso, Kendra Hoekzema, Ruolan Qiu, Karen Clark, Archana Raja, AnneMarie E. Welch, Melanie Sorensen, Carl Baker, Robert S. Fulton, Joel Armstrong, Tina A. Graves-Lindsay, Ahmet M. Denli, Emma R. Hoppe, PingHsun Hsieh, Christopher M. Hill, Andy Wing Chun Pang, Joyce Lee, Ernest T. Lam, Susan K. Dutcher, Fred H. Gage, Wesley C. Warren, Jay Shendure, David Haussler, Valerie A. Schneider, Han Cao, Mario Ventura, Richard K. Wilson, Benedict Paten, Alex Pollen, Evan E. Eichler. High-resolution comparative analysis of great ape genomes. Science, 360(6393). 2018.
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Abstract:
Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.