Towards Complete and Error-Free Genome Assemblies of all Vertebrate Species

Authors

• Arang Rhie, National Human Genome Research Institute (NHGRI)
• Shane A. McCarthy, University of Cambridge
• Olivier Fedrigo, Rockefeller University
• Joana Damas, University of California, Davis
• Giulio Formenti, Rockefeller University
• Sergey Koren, National Human Genome Research Institute (NHGRI)
• Marcela Uliano-Silva, Leibniz-Institut für Zoo- und Wildtierforschung
• William Chow, Wellcome Sanger Institute
• Arkarachai Fungtammasan, DNAnexus
• Juwan Kim, Seoul National University
• Chul Lee, Seoul National University
• Byung June Ko, Department of Food and Animal Biotechnology
• Mark Chaisson, University of Southern California
• Gregory L. Gedman, Rockefeller University
• Lindsey J. Cantin, Rockefeller University
• Francoise Thibaud-Nissen, National Center for Biotechnology Information (NCBI)
• Leanne Haggerty, EMBL’s European Bioinformatics Institute
• Iliana Bista, University of Cambridge
• Michelle Smith, Wellcome Sanger Institute
• Bettina Haase, Rockefeller University
• Jacquelyn Mountcastle, Rockefeller University
• Sylke Winkler, Max Planck Institute of Molecular Cell Biology and Genetics
• Sadye Paez, Rockefeller University
• Jason Howard, Novogene Co., Ltd.
• Sonja C. Vernes, Max Planck Institute for Psycholinguistics
• Tanya M. Lama, University of Massachusetts AmherstFollow
• Frank Grutzner, The University of Adelaide
• Wesley C. Warren, University of Missouri
• Christopher N. Balakrishnan, East Carolina University
• Dave Burt, The University of Queensland
• Julia M. George, Clemson University
• Matthew T. Biegler, Rockefeller University

Document Type

Article

Publication Date

4-29-2021

Publication Title

Nature

Abstract

High-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.

Volume

592

Issue

7856

First Page

737

Last Page

746

DOI

10.1038/s41586-021-03451-0

ISSN

00280836

Version

Author's Accepted Manuscript

Recommended Citation

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.; and Biegler, Matthew T., "Towards Complete and Error-Free Genome Assemblies of all Vertebrate Species" (2021). Biological Sciences: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/bio_facpubs/317