- Kronenberg, Zev N;
- Fiddes, Ian T;
- Gordon, David;
- Murali, Shwetha;
- Cantsilieris, Stuart;
- Meyerson, Olivia S;
- Underwood, Jason G;
- Nelson, Bradley J;
- Chaisson, Mark JP;
- Dougherty, Max L;
- Munson, Katherine M;
- Hastie, Alex R;
- Diekhans, Mark;
- Hormozdiari, Fereydoun;
- Lorusso, Nicola;
- Hoekzema, Kendra;
- Qiu, Ruolan;
- Clark, Karen;
- Raja, Archana;
- Welch, AnneMarie E;
- Sorensen, Melanie;
- Baker, Carl;
- Fulton, Robert S;
- Armstrong, Joel;
- Graves-Lindsay, Tina A;
- Denli, Ahmet M;
- Hoppe, Emma R;
- Hsieh, PingHsun;
- Hill, Christopher M;
- Pang, Andy Wing Chun;
- Lee, Joyce;
- Lam, Ernest T;
- Dutcher, Susan K;
- Gage, Fred H;
- Warren, Wesley C;
- Shendure, Jay;
- Haussler, David;
- Schneider, Valerie A;
- Cao, Han;
- Ventura, Mario;
- Wilson, Richard K;
- Paten, Benedict;
- Pollen, Alex;
- Eichler, Evan E
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.