From a consortium sequence to a unified sequence: the Bacillus subtilis 168 reference genome a decade later.

Valérie Barbe,Tingzhang Wang,Patricia Lenoble,Agnieszka Sekowska,Antoine Danchin,Frank Kunst,Ivan Moszer,Stéphane Cruveiller,Claudine Médigue,Guillaume Meurice,David Vallenet

doi:10.1099/mic.0.027839-0

Abstract

Comparative genomics is the cornerstone of identification of gene functions. The immense number of living organisms precludes experimental identification of functions except in a handful of model organisms. The bacterial domain is split into large branches, among which the Firmicutes occupy a considerable space. Bacillus subtilis has been the model of Firmicutes for decades and its genome has been a reference for more than 10 years. Sequencing the genome involved more than 30 laboratories, with different expertises, in a attempt to make the most of the experimental information that could be associated with the sequence. This had the expected drawback that the sequencing expertise was quite varied among the groups involved, especially at a time when sequencing genomes was extremely hard work. The recent development of very efficient, fast and accurate sequencing techniques, in parallel with the development of high-level annotation platforms, motivated the present resequencing work. The updated sequence has been reannotated in agreement with the UniProt protein knowledge base, keeping in perspective the split between the paleome (genes necessary for sustaining and perpetuating life) and the cenome (genes required for occupation of a niche, suggesting here that B. subtilis is an epiphyte). This should permit investigators to make reliable inferences to prepare validation experiments in a variety of domains of bacterial growth and development as well as build up accurate phylogenies.

Highlights

Bacillus subtilis has been a model for Gram-positive bacteria for more than a century
With subregions devoid of errors and subregions with a substantial amount of variations: typically this fits well with the way the sequencing programme has been organized at its onset in some laboratories, with pieces of 15–20 kb sequenced by students, who were obviously not all able to ensure the http://mic.sgmjournals.org
We noted that some regions, which have not been resequenced by the consortium but taken as published at the time, carry a higher level of errors

Summary

Introduction

Bacillus subtilis has been a model for Gram-positive bacteria for more than a century. Recognized As Safe (GRAS), it is a ubiquitous ingredient of food supplies and a typical member of the A+T-rich Firmicutes, a major clade of the bacterial domain of life. It has been used as the reference model for cell differentiation, and many studies have analysed its welldefined sporulation programme (for reviews see Errington, 2003; Piggot & Hilbert, 2004; Yudkin & Clarkson, 2005). We need references, and comparative genomics is based on approaches that have much in common with the way hieroglyphics were understood using the Rosetta stone This was an obvious reason for the setting up of a B. subtilis genome sequencing programme in 1987. It was obvious, if one wished to couple sequencing to functional knowledge, that the various

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Conclusion