ancient origin and gene mosaicism of the progenitor of mycobacterium tuberculosis古老的起源和基因镶嵌性结核分枝杆菌的祖.pdfVIP

Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis 1* 2 3 4 ¨ 1 3 M. Cristina Gutierrez , Sylvain Brisse , Roland Brosch , Michel Fabre , Bahia Omaıs , Magali Marmiesse , 5 1 Philip Supply , Veronique Vincent ´ ´ ´ ´ ´ ´ ` 1 Laboratoire de Reference des Mycobacteries, Institut Pasteur, Paris, France, 2 Unite de Biodiversite des Bacteries Pathogenes Emergentes, Institut Pasteur, Paris, France, 3 ´ ´ ´ ´ ´ Unite de Genetique Moleculaire Bacterienne, Institut Pasteur, Paris, France, 4 Laboratoire de Biologie Clinique, HIA Percy, Clamart, France, 5 INSERM U629, Institut Pasteur de Lille, Lille, France The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominid