Widespread false gene gains caused by duplication errors in genome assemblies

• Published in: Genome Biology Vol. 23; no. 1; pp. 1 - 205
• Main Authors: Ko, Byung June, Lee, Chul, Kim, Juwan, Rhie, Arang, Yoo, Dong Ahn, Howe, Kerstin, Wood, Jonathan, Cho, Seoae, Brown, Samara, Formenti, Giulio, Jarvis, Erich D., Kim, Heebal
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.09.2022; BMC
• Subjects: Algorithms; Assembly error; Calypte anna; Chromosomes; De novo assembly; Divergence; False duplication; Gene families; Genomes; Genomics; Haplotypes; Ornithorhynchus anatinus; Phasing error; Taeniopygia guttata; Vertebrate genome project
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-022-02764-1

Abstract Background False duplications in genome assemblies lead to false biological conclusions. We quantified false duplications in popularly used previous genome assemblies for platypus, zebra finch, and Anna’s Hummingbird, and their new counterparts of the same species generated by the Vertebrate Genomes Project, of which the Vertebrate Genomes Project pipeline attempted to eliminate false duplications through haplotype phasing and purging. These assemblies are among the first generated by the Vertebrate Genomes Project where there was a prior chromosomal level reference assembly to compare with. Results Whole genome alignments revealed that 4 to 16% of the sequences are falsely duplicated in the previous assemblies, impacting hundreds to thousands of genes. These lead to overestimated gene family expansions. The main source of the false duplications is heterotype duplications, where the haplotype sequences were relatively more divergent than other parts of the genome leading the assembly algorithms to classify them as separate genes or genomic regions. A minor source is sequencing errors. Ancient ATP nucleotide binding gene families have a higher prevalence of false duplications compared to other gene families. Although present in a smaller proportion, we observe false duplications remaining in the Vertebrate Genomes Project assemblies that can be identified and purged. Conclusions This study highlights the need for more advanced assembly methods that better separate haplotypes and sequence errors, and the need for cautious analyses on gene gains.