False gene and chromosome losses in genome assemblies caused by GC content variation and repeats.

Journal Article (Journal Article)

BACKGROUND: Many short-read genome assemblies have been found to be incomplete and contain mis-assemblies. The Vertebrate Genomes Project has been producing new reference genome assemblies with an emphasis on being as complete and error-free as possible, which requires utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. A more thorough evaluation of the recent references relative to prior assemblies can provide a detailed overview of the types and magnitude of improvements. RESULTS: Here we evaluate new vertebrate genome references relative to the previous assemblies for the same species and, in two cases, the same individuals, including a mammal (platypus), two birds (zebra finch, Anna's hummingbird), and a fish (climbing perch). We find that up to 11% of genomic sequence is entirely missing in the previous assemblies. In the Vertebrate Genomes Project zebra finch assembly, we identify eight new GC- and repeat-rich micro-chromosomes with high gene density. The impact of missing sequences is biased towards GC-rich 5'-proximal promoters and 5' exon regions of protein-coding genes and long non-coding RNAs. Between 26 and 60% of genes include structural or sequence errors that could lead to misunderstanding of their function when using the previous genome assemblies. CONCLUSIONS: Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the Vertebrate Genomes Project reference genomes.

Full Text

Duke Authors

Cited Authors

  • Kim, J; Lee, C; Ko, BJ; Yoo, DA; Won, S; Phillippy, AM; Fedrigo, O; Zhang, G; Howe, K; Wood, J; Durbin, R; Formenti, G; Brown, S; Cantin, L; Mello, CV; Cho, S; Rhie, A; Kim, H; Jarvis, ED

Published Date

  • September 27, 2022

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 204 -

PubMed ID

  • 36167554

Pubmed Central ID

  • PMC9516821

Electronic International Standard Serial Number (EISSN)

  • 1474-760X

Digital Object Identifier (DOI)

  • 10.1186/s13059-022-02765-0


  • eng

Conference Location

  • England