RT Journal Article SR Electronic T1 Full-length Genome of a Ogataea polymorpha strain CBS4732 ura3Δ reveals large duplicated segments in subtelomeric regions JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.17.440260 DO 10.1101/2021.04.17.440260 A1 Jia Chang A1 Jinlong Bei A1 Qi Shao A1 Hemu Wang A1 Huan Fan A1 Tung On Yau A1 Wenjun Bu A1 Jishou Ruan A1 Dongsheng Wei A1 Shan Gao YR 2021 UL http://biorxiv.org/content/early/2021/11/15/2021.04.17.440260.abstract AB Background Currently, methylotrophic yeasts (e.g., Pichia pastoris, Ogataea polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains—CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, the O. polymorpha strain CBS4732 ura3Δ (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion.Results In the present study, we have assembled the full-length genome of O. polymorpha HU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5’ and 3’ telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. Particularly, we detected large duplicated segments (LDSs) in the subtelomeric regions and exactly determined all the structural variations (SVs) between CBS4732 and NCYC495.New findings mainly include (1) the genomic differences between HU-11/CBS4732 and NCYC495 include single nucleotide polymorphisms, small insertions and deletions, and only three SVs; (2) six genes were incorporated into CBS4732 from Cyberlindnera jadinii by horizontal gene transfer and may bring HU-11/CBS4732 new biological functions or physiological properties; (3) many recombination events may have occurred on chromosome 4 and 5 of CBS4732 and NCYC495’ ancestors and two large segments were acquired by CBS4732 and NCYC495 from chromosome 6 and C. jadinii during recombination, respectively; and (4) the genome expansion in methylotrophic yeasts is mainly driven by large segment duplication in subtelomeric regions.Conclusions The present study preliminarily revealed the complex relationship between CBS4732, NCYC495, and DL-1. The new findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha CBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of the O. polymorpha strain HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies of Ogataea spp..Competing Interest StatementThe authors have declared no competing interest.TRtandem repeatSTRshort tandem repeatLTRlong terminal repeatmtmitochondrialntnucleotideaaamino acidORFOpen Reading FrameCDSCoding SequenceSVStructural Variation(SNPs)single nucleotide polymorphisms(InDels)insertions and deletions