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Open Access Highly Accessed Research article

Consistent mutational paths predict eukaryotic thermostability

Vera van Noort1, Bettina Bradatsch2, Manimozhiyan Arumugam1, Stefan Amlacher2, Gert Bange25, Chris Creevey3, Sebastian Falk2, Daniel R Mende1, Irmgard Sinning2, Ed Hurt2* and Peer Bork14*

Author Affiliations

1 European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, 69117, Germany

2 Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, Heidelberg, D-69120, Germany

3 Teagasc Animal Bioscience Centre, Grange, Dunsany, Co. Meath, Ireland

4 Max-Delbrück-Centre for Molecular Medicine, Berlin-Buch, Germany

5 Current address: LOEWE Zentrum für synthetische Mikrobiologie, Phillips-University-Marburg, Marburg, Germany

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BMC Evolutionary Biology 2013, 13:7  doi:10.1186/1471-2148-13-7

Published: 10 January 2013

Abstract

Background

Proteomes of thermophilic prokaryotes have been instrumental in structural biology and successfully exploited in biotechnology, however many proteins required for eukaryotic cell function are absent from bacteria or archaea. With Chaetomium thermophilum, Thielavia terrestris and Thielavia heterothallica three genome sequences of thermophilic eukaryotes have been published.

Results

Studying the genomes and proteomes of these thermophilic fungi, we found common strategies of thermal adaptation across the different kingdoms of Life, including amino acid biases and a reduced genome size. A phylogenetics-guided comparison of thermophilic proteomes with those of other, mesophilic Sordariomycetes revealed consistent amino acid substitutions associated to thermophily that were also present in an independent lineage of thermophilic fungi. The most consistent pattern is the substitution of lysine by arginine, which we could find in almost all lineages but has not been extensively used in protein stability engineering. By exploiting mutational paths towards the thermophiles, we could predict particular amino acid residues in individual proteins that contribute to thermostability and validated some of them experimentally. By determining the three-dimensional structure of an exemplar protein from C. thermophilum (Arx1), we could also characterise the molecular consequences of some of these mutations.

Conclusions

The comparative analysis of these three genomes not only enhances our understanding of the evolution of thermophily, but also provides new ways to engineer protein stability.

Keywords:
Thermophily; Comparative genomics; Protein engineering; Eukaryotes; Fungi