High-resolution comparative analysis of great ape genomes

• Published in: Science (American Association for the Advancement of Science) Vol. 360; no. 6393
• Main Authors: Kronenberg, Zev N., Fiddes, Ian T., Gordon, David, Murali, Shwetha, Cantsilieris, Stuart, Meyerson, Olivia S., Underwood, Jason G., Nelson, Bradley J., Chaisson, Mark J. P., 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.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 08.06.2018
• Subjects: Animals; Annotations; Apes; Artificial chromosomes; Assemblies; Assembly; Base pairs; Biological evolution; Brain; Chimpanzees; Comparative Analysis; Complementary DNA; Contig Mapping; Deoxyribonucleic acid; Divergence; DNA; DNA sequencing; Evolution; Evolution, Molecular; Fluorescence in situ hybridization; Gene expression; Gene mapping; Genes; Genetic analysis; Genetic diversity; Genetic testing; Genetic Variation; Genetics; Genome, Human; Genomes; Genomics; Glial stem cells; Gorilla gorilla; Hominidae - genetics; Homo sapiens; Humans; Inversions; Molecular chains; Molecular Sequence Annotation; Monkeys & apes; Neural stem cells; Neuronal-glial interactions; Nucleotide sequence; Organoids; Pan troglodytes; Pluripotency; Pongo; Regulatory sequences; Scaffolding; Scaffolding (Teaching Technique); Sequence Analysis, DNA; Stem cell transplantation; Stem cells; Synteny; Transcription
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aar6343

Most nonhuman primate genomes generated to date have been “humanized” owing to their many gaps and the reliance on guidance by the reference human genome. To remove this humanizing effect, Kronenberg et al. generated and assembled long-read genomes of a chimpanzee, an orangutan, and two humans and compared them with a previously generated gorilla genome. This analysis recognized genomic structural variation specific to humans and particular ape lineages. Comparisons between human and chimpanzee cerebral organoids showed down-regulation of the expression of specific genes in humans, relative to chimpanzees, related to noncoding variation identified in this analysis. Science , this issue p. eaar6343 Analysis of long-read great ape and human genomes identifies human-specific changes affecting brain gene expression. 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.