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MBE Advance Access published online on June 1, 2007

Molecular Biology and Evolution, doi:10.1093/molbev/msm111
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© 2007 The Authors.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (
http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Research Article

Contribution of Horizontally Acquired Genomic Islands to the Evolution of the Tubercle Bacilli

Jennifer Becq1, Maria Cristina Gutierrez2, Vania Rosas-Magallanes3, Jean Rauzier3, Brigitte Gicquel3, Olivier Neyrolles3,4,* and Patrick Deschavanne1,*

1 Genomics and Molecular Bioinformatics, INSERM U726, University Paris 7, Paris, France
2 Unit of Biodiversity of Emerging Pathogenic Bacteria, Institut Pasteur, Paris, France
3 Unit of Mycobacterial Genetics, Institut Pasteur, Paris, France
4 Centre National de la Recherche Scientifique, URA 2172, Paris, France

Correspondence should be sent to O. Neyrolles, Institut Pasteur, Unit of Mycobacterial Genetics, 28 rue du Dr Roux, 75015 Paris, France, Tel: +33 (0)1 45 68 88 40, FAX: +33 (0)1 45 68 88 43, e-mail: neyrolle{at}pasteur.fr, or to P. Deschavanne, EBGM Inserm U726 - Université Paris 7, Case 7113, 2 place Jussieu, Paris 75251 Cedex 05, France, Tel: +33 (0)1 44 27 77 12, FAX: +33 (0)1 43 26 38 30, e-mail: patrick.deschavanne{at}ebgm.jussieu.fr

Received for publication December 14, 2006. Revision received April 19, 2007. Accepted for publication May 29, 2007.

The contribution of horizontal gene transfer (HGT) to the evolution of Mycobacterium tuberculosis — the main causal agent of tuberculosis in humans — and closely related members of the M. tuberculosis complex remains poorly understood. Using a combination of genome-wide parametric analyses, we have identified 48 M. tuberculosis chromosomal regions with atypical characteristics, potentially due to HGT. These specific regions account for 4.5 % of the genome (199 kb) and include 256 genes. Many display features typical of the genomic islands found in other bacteria, including residual material from mobile genetic elements, flanking direct repeats, insertion in the vicinity of tRNA sequences, and genes with putative or documented virulence functions. Southern blotting analysis of 9 of these 48 regions confirmed their presence in "Mycobacterium prototuberculosis", the ancestral species of the M. tuberculosis complex. Finally, our results strongly suggest that the ancestor of the tubercle bacilli was an environmental bacillus that exchanged genetic material with other bacterial species, including Proteobacteria in particular, present in its surroundings. This study describes a rational approach to searching for mycobacterial virulence genes, and highlights the importance of dissecting gene transfer networks to improve our understanding of mycobacterial pathogenicity and evolution.

Key Words: Horizontal gene transfer • Mycobacterium tuberculosis complex • Tuberculosis • Virulence


* These authors share senior authorship.


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