Co-evolution of Mycobacterium tuberculosis and Homo sapiens

Abstract

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future 'genome-to-genome' studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines.

Keywords: adaptation; host; pathogen; selection; virulence.

Figure 1

Whole-genome phylogeny of 220 strains of MTBC. Bootstrap support for the main branches after inference with Neighbor-joining (left) and Maximum-likelihood (right) analyses are shown. The grey circle indicates the ‘modern’ strains (see main text). Scale bars indicate substitutions per site. The occurrence of the TbD1 deletion is indicated with an asterisk. Adapted from Comas et al. (29).

Figure 2

Simplified schematic illustrating the phylogenetic relationships of animal strains based on different phylogenies published previously ((31,40,49,51,52)). The length of the branches does not reflect real phylogenetic distances. Dashed branches represent putative relative relationships. The phylogenetic positions of genomic deletions discussed in the main text and of the mutations in the phoPR genes (54) are indicated. The geographical and host ranges of the animal lineages do not include reports from zoos, as those were considered incidental infections.

Figure 3

Comparison of the MTBC phylogeny based on 220 genomes (left) and a phylogeny derived from 4955 mitochondrial genomes representative of the main human mitochondrial haplogroups (right). The color coding highlights the similarities in tree topology, and geographic distribution between MTBC strains and the main human mitochondrial macrohaplogroups (black, African clades: MTBC Lineages 5 and 6, human mitochondrial macrohaplogroups L0–L3; pink, Southeast Asian and Oceania clades: MTBC Lineage 1, human mitochondrial macrohaplogroup M; blue, Eurasian clades: MTBC Lineages 2, 3, and 4, human mitochondrial macrohaplogroup N). MTBC Lineage 7 has only been found in Ethiopia, and its correlation with any of the three main human haplogroups remains unclear. Figure from Comas et al. (29).

Figure 4

Geographic and genetic structure of a global sample of MTBC genomes. Adapted from Pepperell et al. (107). (A) Maximum clade credibility phylogeny inferred from genome-wide MTBC SNP data. Tips are colored by the geographic origin of the MTBC isolate (see key). Modifications: the lineage nomenclature (indicated with an asterisk) and color codes used by Comas et al. (29) was added to the original tree; the red arrows indicate the calibration points used for dating the most recent common ancestor of MTBC. (B) Countries of origin for MTBC isolates used in this study are shown as colored dots on the global map. One dot is shown per country but some countries were represented by >1 MTBC isolate. Colors correspond to global regions (see key). (C) Phylogeny of global human populations based on Y chromosome data (120). Tips are colored according to the same scheme as the MTBC phylogeny (A). Modifications: the names of the relevant human Y haplogroups were added (indicated with an asterisk) and color coded as in Comas et al. (29).

Figure 5

Summary of the most important archeological findings and molecular evidence indicating the presence of MTBC in human remains. All studies reported MTBC in human skeletons or mummies except in Rothschild et al. (133). (i) Human movements possibly involved in the expansion of MTBC; (ii) Intervals for coalescent times (95% HPD) concerning the MRCA of different MTBC lineages obtained from the two most discrepant inferences (40,29); (iii) Interpretation of both archeological and biomolecular findings. For a better understanding of the molecular typing techniques see Coscolla and Gagneux (15). For each molecular marker, the number of archeological specimens containing DNA with that specific marker is indicated within parentheses. BP, before present; spol., spoligotyping pattern; und., undefined; WGS, whole-genome sequencing.