Research article

Insights into the evolutionary history of tubercle bacilli as disclosed by genetic rearrangements within a PE_PGRS duplicated gene pair

Anis Karboul^{* 1} , Nicolaas C Gey van Pittius^{* 2} , Amine Namouchi¹ , Véronique Vincent³ , Christophe Sola^4,11 , Nalin Rastogi⁴ , Philip Suffys⁵ , Michel Fabre⁶ , Angel Cataldi⁷ , Richard C Huard⁸ , Natalia Kurepina⁹ , Barry Kreiswirth⁹ , John L Ho¹⁰ , M Cristina Gutierrez³ and Helmi Mardassi¹

¹Unit of Typing and Genetics of Mycobacteria, Institut Pasteur de Tunis, 13 Place Pasteur, 1002 Tunis-Belvédère, Tunis, Tunisie

²DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, South Africa

³Laboratoire de Référence des Mycobactéries, Institut Pasteur, Paris, France

⁴Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Guadeloupe

⁵Laboratory of Molecular Biology and Diagnosis of Infectious Diseases, Oswaldo Cruz Institute, Brazil

⁶Laboratoire de Biologie Clinique, HIA Percy, Clamart, France

⁷Instituto de Biotecnologia, INTA, Castelar, Buenos Aires, Argentina

⁸Clinical Microbiology Service and the Department of Pathology, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY, USA

⁹Public Health Research Institute (PHRI), Newark, New Jersey, USA

¹⁰Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, NY, USA

¹¹Unit of Mycobacterial genetics, Institut Pasteur, Paris, France

author email corresponding author email* Contributed equally

BMC Evolutionary Biology 2006, 6:107doi:10.1186/1471-2148-6-107

Published:	12 December 2006

Abstract

Background

The highly homologous PE_PGRS (Proline-glutamic acid_polymorphic GC-rich repetitive sequence) genes are members of the PE multigene family which is found only in mycobacteria. PE genes are particularly abundant within the genomes of pathogenic mycobacteria where they seem to have expanded as a result of gene duplication events. PE_PGRS genes are characterized by their high GC content and extensive repetitive sequences, making them prone to recombination events and genetic variability.

Results

Comparative sequence analysis of Mycobacterium tuberculosis genes PE_PGRS17 (Rv0978c) and PE_PGRS18 (Rv0980c) revealed a striking genetic variation associated with this typical tandem duplicate. In comparison to the M. tuberculosis reference strain H37Rv, the variation (named the 12/40 polymorphism) consists of an in-frame 12-bp insertion invariably accompanied by a set of 40 single nucleotide polymorphisms (SNPs) that occurs either in PE_PGRS17 or in both genes. Sequence analysis of the paralogous genes in a representative set of worldwide distributed tubercle bacilli isolates revealed data which supported previously proposed evolutionary scenarios for the M. tuberculosis complex (MTBC) and confirmed the very ancient origin of "M. canettii" and other smooth tubercle bacilli. Strikingly, the identified polymorphism appears to be coincident with the emergence of the post-bottleneck successful clone from which the MTBC expanded. Furthermore, the findings provide direct and clear evidence for the natural occurrence of gene conversion in mycobacteria, which appears to be restricted to modern M. tuberculosis strains.

Conclusion

This study provides a new perspective to explore the molecular events that accompanied the evolution, clonal expansion, and recent diversification of tubercle bacilli.