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 Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries.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.

Towards complete and error-free genome assemblies of all vertebrate species / A. Rhie, S.A. Mccarthy, O. Fedrigo, J. Damas, G. Formenti, S. Koren, M. Uliano-Silva, W. Chow, A. Fungtammasan, J. Kim, C. Lee, B.J. Ko, M. Chaisson, G.L. Gedman, L.J. Cantin, F. Thibaud-Nissen, L. Haggerty, I. Bista, M. Smith, B. Haase, J. Mountcastle, S. Winkler, S. Paez, J. Howard, S.C. Vernes, T.M. Lama, F. Grutzner, W.C. Warren, C.N. Balakrishnan, D. Burt, J.M. George, M.T. Biegler, D. Iorns, A. Digby, D. Eason, B. Robertson, T. Edwards, M. Wilkinson, G. Turner, A. Meyer, A.F. Kautt, P. Franchini, H.W. Detrich, H. Svardal, M. Wagner, G.J.P. Naylor, M. Pippel, M. Malinsky, M. Mooney, M. Simbirsky, B.T. Hannigan, T. Pesout, M. Houck, A. Misuraca, S.B. Kingan, R. Hall, Z. Kronenberg, I. Sović, C. Dunn, Z. Ning, A. Hastie, J. Lee, S. Selvaraj, R.E. Green, N.H. Putnam, I. Gut, J. Ghurye, E. Garrison, Y. Sims, J. Collins, S. Pelan, J. Torrance, A. Tracey, J. Wood, R.E. Dagnew, D. Guan, S.E. London, D.F. Clayton, C.V. Mello, S.R. Friedrich, P.V. Lovell, E. Osipova, F.O. Al-Ajli, S. Secomandi, H. Kim, C. Theofanopoulou, M. Hiller, Y. Zhou, R.S. Harris, K.D. Makova, P. Medvedev, J. Hoffman, P. Masterson, K. Clark, F. Martin, K. Howe, P. Flicek, B.P. Walenz, W. Kwak, H. Clawson, M. Diekhans, L. Nassar, B. Paten, R.H.S. Kraus, A.J. Crawford, M.T.P. Gilbert, G. Zhang, B. Venkatesh, R.W. Murphy, K. Koepfli, B. Shapiro, W.E. Johnson, F. Di Palma, T. Marques-Bonet, E.C. Teeling, T. Warnow, J.M. Graves, O.A. Ryder, D. Haussler, S.J. O'Brien, J. Korlach, H.A. Lewin, K. Howe, E.W. Myers, R. Durbin, A.M. Phillippy, E.D. Jarvis. - In: NATURE. - ISSN 0028-0836. - 592:7856(2021 Apr), pp. 737-746. [10.1038/s41586-021-03451-0]

Towards complete and error-free genome assemblies of all vertebrate species

G. Formenti;S. Secomandi;
2021

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.
vertebrate genomes; long-reads; complete assembly
Settore BIOS-14/A - Genetica
   Great ape genome variation now and then: current diversity and genomic relics of extinct primates
   ApeGenomeDiversity
   European Commission
   Horizon 2020 Framework Programme
   864203

   The genomic basis of convergent evolution in modern sloths (Xenarthra, Mammalia)
   CONVGENOMS
   European Commission
   Horizon 2020 Framework Programme
   750747
apr-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
s41586-021-03451-0 (1).pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 9.53 MB
Formato Adobe PDF
9.53 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1141035
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 1101
  • ???jsp.display-item.citation.isi??? 571
social impact