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Nature Reviews Microbiology
3,
859-869
(2005);
doi:10.1038/nrmicro1268
DISCOVERING NOVEL BIOLOGY BY IN SILICO ARCHAEOLOGY

Thijs J. G. Ettema, Willem M. de Vos & John van der Oost
about the authors
Abstract
Archaea are prokaryotes that evolved in parallel with bacteria. Since the discovery of the distinct status of the Archaea, extensive physiological and biochemical research has been conducted to elucidate the molecular basis of their remarkable lifestyle and their unique biology. Here, we discuss how in-depth comparative genomics has been used to improve the annotation of archaeal genomes. Combined with experimental verification, bioinformatic analysis contributes to the ongoing discovery of novel metabolic conversions and control mechanisms, and as such to a better understanding of the intriguing biology of the Archaea.
Summary
- Archaea are prokaryotes that have evolved in parallel with bacteria. Since the discovery of the distinct status of the archaea, extensive physiological and biochemical research is starting to reveal the molecular basis of their remarkable lifestyle and unique biology.
- Analysis of the first completely sequenced archaeal genomes revealed mysterious 'genomescapes', encoding incomplete pathways and many genes for which no function could be assigned. With the development of archaeal model organisms, and efficient genetic systems still being in their infancy, other methods had to be explored to tackle this problem.
- With over 20 sequenced archaeal genomes available, several conceptually different types of comparative genomics analyses have proven to be a powerful tool for prediction of gene function. As such, these analyses can be used to improve the functional annotation of archaeal genomes and serve as a lead for experimental analysis.
- In this review, we discuss how these different types of 'genome context' analysis, often in combination with subsequent experimental verification, have resulted in the functional identification of novel archaeal systems and several missing links that continue to exist in archaeal metabolic pathways.
- In the near future, it is to be expected that the integration of comparative and functional genomics data resulting from large-scale experimental design (systems biology) will greatly contribute to a better understanding of the intriguing biology of the archaea.

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