Figure 1.
Evolutionary relationships of the Mycobacterium tuberculosis complex.
(A) Unrooted MIRU Neighbour-joining phenogram depicting genetic distance relationships among tubercle bacilli isolates based on Nei et al.'s DA distances. (B) Rooted MIRU population Neighbour-joining tree based on genetic distance. M. prototuberculosis was used as an outgroup. Values on the nodes represent the percentage of bootstrap replicates over individuals (N = 1000) showing the particular nodes. Branch lengths are proportional to the genetic distance between the tubercle lineages. It is noteworthy that low bootstrap values within clade 2 prevent us from drawing further inferences on the branching order in this clade (see also main text). Wa, West-Africa. (C) Population structure of 20 MTBC clonal lineages using the no-admixture model, where K = 3. Each colour represents one cluster, and the length of the color segment shows the strains' estimated proportion of membership in that cluster. Results shown are averages over 10 STRUCTURE runs. For clarity, strains codes are also given according to Gagneux et al. (2006).
Figure 2.
Genetic variability in the different MTBC lineages.
(A and B) MIRU allelic richness in each population within clade 1 and 2 respectively. Rarefaction included eight isolates per population (smaller populations were not considered in this analysis. (C) Clades mean allelic richness. Notice that the difference between clade 1 and 2 is not significant (t-test, P = 0.08).
Figure 3.
Calculated posterior mean for MIRU-VNTR mutation rate among loci using the MSVAR algorithm.
This graph corresponds to the output obtained for the Haarlem population sample and the 95% interval confidence is given (red dotted lines).
Table 1.
Estimated Times (in years) since the most recent common ancestor (TMRCA).
Figure 4.
Detection of recent expansion in different MTBC lineages.
(A) Posterior distribution of M. bovis TMRCA, including the 95% confidence interval and density plots of the marginal posterior distribution of log (N0), where N0 is the current effective number of chromosomes and log (Nd), where Nd is the number of chromosomes before expansion. (B) Same plots for EAI. ta is expressed in years (±SD) and denotes the time that has elapsed since the population growth began.
Table 2.
Time to the most recent common ancestor (TMRCA), time elapsed since the last expansion began (ta) and growth rate estimates based on the MSVAR software.
Figure 5.
M. tuberculosis evolutionary scenario (out of Mesopotamia).
The main migrations events are numbered and correspond to: 1, M. prototuberculosis, the ancestor of the MTBC, this bacterium reached the Fertile Crescent some 40,000 years ago by sea or land; 2 and 3, two distinct basal lineages arose, EAI and LAM and spread out of Mesopotamia some 10, 000 years ago; 4, 5 and 6, later on (8–5000 years ago) derived populations from clade 1 followed main human migration patterns to Africa, Asia and Europe, giving rise to locally adapted tubercle strains and further diversifications. Note that the depicted borders are “artificial” and are used for the demonstration. Global movements and intercontinental exchanges tend to blur this phylogenetic signal though strong enough to be detected nowadays.