Towards complete and error-free genome assemblies of all vertebrate species
Authors: Rhie Arang , McCarthy Shane A. , Fedrigo Olivier , Damas Joana , Formenti Giulio , Koren Sergey , Uliano-Silva Marcela , Chow William , Fungtammasan Arkarachai , Kim Juwan , Lee Chul , Ko Byung June , Chaisson Mark , Gedman Gregory L. , Cantin Lindsey J. , Thibaud-Nissen Francoise , Haggerty Leanne , Bista Iliana , Smith Michelle , Haase Bettina , Mountcastle Jacquelyn , Winkler Sylke , Paez Sadye , Howard Jason , Vernes Sonja C. , Lama Tanya M. , Grutzner Frank , Warren Wesley C. , Balakrishnan Christopher N. , Burt Dave , George Julia M. , Biegler Matthew T. , Iorns David , Digby Andrew , Eason Daryl , Robertson Bruce , Edwards Taylor , Wilkinson Mark , Turner George , Meyer Axel , Kautt Andreas F. , Franchini Paolo , Detrich H. William , Svardal Hannes , Wagner Maximilian , Naylor Gavin J. P. , Pippel Martin , Malinsky Milan , Mooney Mark , Simbirsky Maria , Hannigan Brett T. , Pesout Trevor , Houck Marlys , Misuraca Ann , Kingan Sarah B. , Hall Richard , Kronenberg Zev , Sović Ivan , Dunn Christopher , Ning Zemin , Hastie Alex , Lee Joyce , Selvaraj Siddarth , Green Richard E. , Putnam Nicholas H. , Gut Ivo , Ghurye Jay , Garrison Erik , Sims Ying , Collins Joanna , Pelan Sarah , Torrance James , Tracey Alan , Wood Jonathan , Dagnew Robel E. , Guan Dengfeng , London Sarah E. , Clayton David F. , Mello Claudio V. , Friedrich Samantha R. , Lovell Peter V. , Osipova Ekaterina , Al-Ajli Farooq O. , Secomandi Simona , Kim Heebal , Theofanopoulou Constantina , Hiller Michael , Zhou Yang , Harris Robert S. , Makova Kateryna D. , Medvedev Paul , Hoffman Jinna , Masterson Patrick , Clark Karen , Martin Fergal , Howe Kevin , Flicek Paul , Walenz Brian P. , Kwak Woori , Clawson Hiram , Diekhans Mark , Nassar Luis , Paten Benedict , Kraus Robert H. S. , Crawford Andrew J. , Gilbert M. Thomas P. , Zhang Guojie , Venkatesh Byrappa , Murphy Robert W. , Koepfli Klaus-Peter , Shapiro Beth , Johnson Warren E. , Di Palma Federica , Marques-Bonet Tomas , Teeling Emma C. , Warnow Tandy , Graves Jennifer Marshall , Ryder Oliver A. , Haussler David , O’Brien Stephen J. , Korlach Jonas , Lewin Harris A. , Howe Kerstin , Myers Eugene W. , Durbin Richard , Phillippy Adam M. , Jarvis Erich D. 
Published: April 2021

AbstractHigh-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.