Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis - PubMed (original) (raw)

Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis

M Cristina Gutierrez et al. PLoS Pathog. 2005 Sep.

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.

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Conflict of interest statement

Competing interests. The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Phylogenetic Position of the Tubercle Bacilli within the Genus Mycobacterium

The blue triangle corresponds to tubercle bacilli sequences that are identical or differing by a single nucleotide. The sequences of the genus Mycobacterium that matched most closely to those of M. tuberculosis were retrieved from the BIBI database (

http://pbil.univ-lyon.fr/bibi/

) and aligned with those obtained for 17 smooth and MTBC strains. The unrooted neighbor-joining tree is based on 1,325 aligned nucleotide positions of the 16S rRNA gene. The scale gives the pairwise distances after Jukes-Cantor correction. Bootstrap support values higher than 90% are indicated at the nodes.

Figure 2

Figure 2. Splits Graph of the 17 Concatenated Sequences of the Six Housekeeping Genes

The nodes represent strains and are depicted as small red (smooth tubercle bacilli) or blue (MTBC members) squares. The scale bar represents Hamming distance. Numbers at the edges represent the percent bootstrap support of the splits obtained after 1,000 replicates. The fit was 61.7%. Note that the branching order of MTBC strains is weakly supported, and it should therefore not be seen as contradicting previous evolutionary hypotheses based on deletion patterns [16].

Figure 3

Figure 3. Nucleotide Polymorphism Detected in the Six Housekeeping Genes for the 17 Sequenced Strains

(A) Location of the genes on the genome of M. tuberculosis H37Rv. Note that gyrB and gyrA are adjacent. (B) Pattern of polymorphic sites revealing mosaicism of sequences. Colored blocks correspond to sequence stretches in the smooth strains that are similar or identical to the sequences in the MTBC. Boxes correspond to blocks of consecutive nucleotides in smooth strains that differ by at least three nucleotides from M. tuberculosis H37Rv. The last column indicates the allele number for each gene. Letters N and s indicate nonsynonymous and synonymous substitutions, respectively.

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