How old are bacterial pathogens?

Abstract

Only few molecular studies have addressed the age of bacterial pathogens that infected humans before the beginnings of medical bacteriology, but these have provided dramatic insights. The global genetic diversity of Helicobacter pylori, which infects human stomachs, parallels that of its human host. The time to the most recent common ancestor (tMRCA) of these bacteria approximates that of anatomically modern humans, i.e. at least 100 000 years, after calibrating the evolutionary divergence within H. pylori against major ancient human migrations. Similarly, genomic reconstructions of Mycobacterium tuberculosis, the cause of tuberculosis, from ancient skeletons in South America and mummies in Hungary support estimates of less than 6000 years for the tMRCA of M. tuberculosis Finally, modern global patterns of genetic diversity and ancient DNA studies indicate that during the last 5000 years plague caused by Yersinia pestis has spread globally on multiple occasions from China and Central Asia. Such tMRCA estimates provide only lower bounds on the ages of bacterial pathogens, and additional studies are needed for realistic upper bounds on how long humans and animals have suffered from bacterial diseases.

Keywords: ancient DNA; comparative genomics; gastritis; history of disease; plague; tuberculosis.

Figure 1.

Population structure, dated phylogeny and ancient migrations of Helicobacter pylori based on sequences of seven housekeeping gene fragments. (a) Global population structure (based on electronic supplementary material, figure S3 [25] updated with additional data from [22]). (b,c) Migrations into the Pacific of hspMaori and hpSahul (modified from figure 1 of [22]). (b) A phylogenetic tree of hspMaori, a subpopulation of hpEastAsia, shows patterns of serial descent from bacteria from indigenous Taiwanese of six ethnic groupings through isolates from Filipinos, Melanesians and Polynesians. (c) Frequencies of hspMaori (orange) and hpSahul (red) in pie charts according to geographical source. (c inset; Taiwan subdivided by indigenous ethnic group; number of hspMaori/number of all H. pylori (Austronesian language family)). (d) Quantitative parallel patterns of pairwise genetic distances between H. pylori and human mtDNA samples from corresponding geographical areas. (source: figure 7 of [20]). (e) Comparison of phylogenetic tree of H. pylori housekeeping gene fragments (left) and human mtDNA (right) (source: figure 6 of [20]). African lineages are shown on a green background, whereas the background for lineages outside Africa is light blue. San clades are purple, non-San clades are orange and H. acinonychis is yellow. San mtDNA lineages that were identified in this study are shown as white lines.

Figure 2.

Plague pandemics and phylogeny of Yersinia pestis. (a) Manual concatenation of the topologies of phylogenies described in [30], [16] and [31], including additional ancient genomes and genotypes (see below), plus proposed mnemonics for those populations. Sources of ancient genomes and genotypes: the Bronze Age (0.PRE1, 0.PRE2; grey) [31], the Justinianic Pandemic (0.ANT4; blue) [32]; the Black Death (1.PRE1; maroon; London, 1348 [33]; Barcelona 1300–1420 [34]; SNP-based genotypes from Germany (fourteenth and seventeenth centuries) [35]) and descendent branches of 1.PRE from Ellwangen (1.PRE1B; 1485–1627) [34] and Marseille (1.PRE1.A, 1722) [36]). One SNP further along branch 1 are the populations 1.PRE2 (London, 1362–1400 [36] and the related low-resolution genotype found in Berg-Op-Zoom, The Netherlands from the fourteenth century [37]; green). One further SNP down the branch is a short branch leading to a genome from Western Asia (1.PRE3; Bolgar City, Tatarstan, Russia; light blue) [34]. (b,c) Maps of the spread of the Justinianic (b) and second plague (c) pandemics. With permission from Elisabeth Carniel. (d) Reconstruction of waves of transmission of individual lineages within the third pandemic. Modified from supplementary figure 3 from [30] (http://research.ucc.ie/NG1/index.html).

Figure 3.

Estimated tMRCA of Mycobacterium tuberculosis. (a) Phylogenetic tree of genomes from lineages L1–L7 that infect humans, lineages that are associated with animal infections, and ancient genomes from Peruvians (modified from figure 3a from [55]). (b) Phylogenetic tree of 1582 genomes of lineage 4 of M. tuberculosis shows the location within the tree of 4 high coverage (blue lines and dots) and 10 low coverage genomes (red dots) from metagenomic sequences of mummified bodies in Hungary [56]. (c) Principles of phylogenetic placement with MGPlacer [56] for the mapping results in part (b). Polymorphisms that are identified by mapping short reads to a reference genome are traced down a pre-calculated phylogeny until no further SNPs match the branches leading to existing genotypes. The diameters of the pie charts reflect the number of known genotypes for each node, whereas the shaded slices indicate the proportion of characteristic SNPs within each pie that were found in the metagenomic reads. Parts (b) and (c) from figure 3 of [56].