High-resolution comparative analysis of great ape genomes.
Zev N KronenbergIan T FiddesDavid GordonShwetha MuraliStuart CantsilierisOlivia S MeyersonJason G UnderwoodBradley J NelsonMark J P ChaissonMax L DoughertyKatherine M MunsonAlex R HastieMark E DiekhansFereydoun HormozdiariNicola LorussoKendra HoekzemaRuolan QiuKaren ClarkArchana RajaAnneMarie E WelchMelanie SorensenCarl BakerRobert S FultonJoel ArmstrongTina A Graves-LindsayAhmet M DenliEmma R HoppePingHsun HsiehChristopher M HillAndy Wing Chun PangJoyce LeeErnest T LamSusan K DutcherFred H GageWesley C WarrenJay ShendureDavid HausslerValerie A SchneiderHan CaoMario VenturaRichard K WilsonBenedict PatenAlex Aaron PollenEvan E EichlerPublished in: Science (New York, N.Y.) (2018)
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.