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Open Access Highly Accessed Research article

Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1

Nikolai V Ravin1, Michael A Eldarov1, Vitaly V Kadnikov1, Alexey V Beletsky1, Jessica Schneider3, Eugenia S Mardanova1, Elena M Smekalova2, Maria I Zvereva2, Olga A Dontsova2, Andrey V Mardanov1 and Konstantin G Skryabin1*

Author Affiliations

1 Centre “Bioengineering” of RAS, Prosp. 60-let Oktyabrya, bld. 7-1, Moscow 117312, Russia

2 Faculty of Chemistry, Lomonosov Moscow State University, 119999 Moscow, Russia and Belozersky Institute, Moscow State University, Leninskie Gory 1, Bldg. 40, 119991 Moscow, Russia

3 Institute for Bioinformatics, Center for Biotechnology, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany

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BMC Genomics 2013, 14:837  doi:10.1186/1471-2164-14-837

Published: 27 November 2013

Abstract

Background

Hansenula polymorpha DL1 is a methylotrophic yeast, widely used in fundamental studies of methanol metabolism, peroxisome biogenesis and function, and also as a microbial cell factory for production of recombinant proteins and metabolic engineering towards the goal of high temperature ethanol production.

Results

We have sequenced the 9 Mbp H. polymorpha DL1 genome and performed whole-genome analysis for the H. polymorpha transcriptome obtained from both methanol- and glucose-grown cells. RNA-seq analysis revealed the complex and dynamic character of the H. polymorpha transcriptome under the two studied conditions, identified abundant and highly unregulated expression of 40% of the genome in methanol grown cells, and revealed alternative splicing events. We have identified subtelomerically biased protein families in H. polymorpha, clusters of LTR elements at G + C-poor chromosomal loci in the middle of each of the seven H. polymorpha chromosomes, and established the evolutionary position of H. polymorpha DL1 within a separate yeast clade together with the methylotrophic yeast Pichia pastoris and the non-methylotrophic yeast Dekkera bruxellensis. Intergenome comparisons uncovered extensive gene order reshuffling between the three yeast genomes. Phylogenetic analyses enabled us to reveal patterns of evolution of methylotrophy in yeasts and filamentous fungi.

Conclusions

Our results open new opportunities for in-depth understanding of many aspects of H. polymorpha life cycle, physiology and metabolism as well as genome evolution in methylotrophic yeasts and may lead to novel improvements toward the application of H. polymorpha DL-1 as a microbial cell factory.

Keywords:
Hansenula polymorpha; Genome; Methylotrophic yeasts; RNA-seq; Yeast evolution