Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis

Abstract

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 hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success.

Tuberculosis and leprosy in Italy. New skeletal evidence

“…At this moment, the most ancient real cases known in the world are: for TB an Eastern Mediterranean (Israel) Neolithic settlement dated about 9000 BP (Hershkovitz et al, 2008) while for leprosy there is a case found in India and dated 2000 BE (Robbins et al, 2009). Molecular studies have shown that both diseases started from Africa following the migration paths of the first human groups in the direction of Asia (Gutierrez et al, 2005;Monot et al, 2005). It has been shown that TB was widespread in Italy in the past (Fig.…”

Advances in tuberculosis

“…A more recent report of TB infection found in humans dates back to 9,000 years ago (Hershkovitz et al, 2008). M. tuberculosis complex (MTBC), the group of mycobacteria causing tuberculosis is estimated to have been present for over 3 million years (Gutierrez et al, 2005), diverged from its kin, Mycobacterium leprae, the causative agent of leprosy, over 33 million years earlier.…”

Pulmonary Tuberculosis and Mycobacterium Tuberculosis: Modern Molecular Epidemiology and Perspectives

“…One important outgrowth of the phylogenetic revolution is the recognition that phylogenetic trees provide an important and appropriate context to address questions in a variety of disciplines such as molecular epidemiology and evolutionary biology. More and more, the phylogenetic approach is used to explore the population structure and to infer the system of reproduction of various organisms [58,83].These analyses contribute complementary information beyond population genetics studies, such as genetic structuring in a population, identification of a genetically individualized entity, for example, cryptic species and epidemics. Furthermore, the congruence or incongruence of different gene phylogenies also provides substantial insight into the population structure.…”

“…Recently, a study based on phylogenetic and sequence analysis was published by Gutierrez et al [83] in order to unravel the evolutionary success of MTB. Members of the MTBC suggested representing the clonal progeny of a single successful ancestor, resulting from a recent evolutionary bottleneck that occurred 20,000-35,000 years ago [177].…”

“…Members of the MTBC suggested representing the clonal progeny of a single successful ancestor, resulting from a recent evolutionary bottleneck that occurred 20,000-35,000 years ago [177]. Gutierrez et al [83] identified the progenitor of MTBC, which includes M. canettii (already suggested by Brosch et al [20]), a rare tubercle bacillus with an unusual smooth colony phenotype [199], and other smooth tubercle bacilli from Djibouti. These authors proposed to call this group of strains M. prototuberculosis species.…”