Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

Abstract

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6(Quebec) genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710-1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

Fig. 1.

Fur trade geography, regional frequencies of M. tuberculosis lineages, and historical timeline. (A) Map of Canada from Natural Resources Canada (49). The main fur trade canoe route from the St. Lawrence River to the Beaufort Sea (Montreal route) is shown in light blue. Canoe routes from Hudson's Bay to the interior are shown in red. Geography of canoe routes is based on a map by A. Ray in ref. and was checked against a map of fur trade posts (50). Geography of railways, steamship lines, and areas classified as remote/traditional on the basis of archival evidence (all ca. 1920) are from figure 38 in ref. and ref. . Proportional lineage frequencies of M. tuberculosis isolates are shown as pie charts in the corresponding province (see also Table S1). Nomenclature of M. tuberculosis lineages is from refs. and . Pie charts are the same size for clarity, although total sample sizes differed among populations. Lineage frequencies were unavailable for the MB population. (B) Events shown in the timeline are the founding of New France (Quebec) in 1608; incursion of fur traders to the Northwest around 1710; British conquest of New France (and end of migration from France to Quebec) in 1760; merger of North West Company and Hudson's Bay Company (HBC) in 1820 (with subsequent abandonment of the Montreal route in favor of Hudson's Bay routes); completion of the Canadian Pacific Railway (CPR) in 1885, by which time Western buffalo herds were severely depleted; and, finally, widespread use of bush planes to reach remote areas, starting in the 1930s. Gray boxes indicate the estimated timing of processes in M. tuberculosis demographic history: dispersal of M. tuberculosis to indigenous populations (light gray), and expansion of M. tuberculosis populations as a result of shifts in host ecology (dark gray).

Fig. 2.

Minimum spanning tree of minisatellite haplotypes (12 loci) from M. tuberculosis within the DS6^Quebec lineage, in QU, ON, SK, and AB populations. The size of nodes is proportional to the frequency of TB cases associated with that M. tuberculosis haplotype. Scale is indicated by the line at the bottom of the figure, which represents a difference of one minisatellite repeat. Minisatellites were not available from the MB population.

Fig. 3.

Genetic diversity of M. tuberculosis populations. (A) Number of distinct RFLP haplotypes as a function of the number of sampled chromosomes obtained using rarefaction (Materials and Methods). Populations include QU, MB, SK, and AB; ON is not included because of its low sample size (SI Results). Every fourth data point is presented for clarity. (B) RFLP haplotype diversity (Shannon index), correcting for sample size by repeatedly sampling the total number of isolates in the smallest sample from each population (NRS, n = 123). Boxplots indicate values obtained over all samples; value for the smallest sample (NRS) is indicated by a line. Populations are as in the left panel, except that SK is split into RS and NRS populations. Although Manitoba contains both remote and nonremote regions (Fig. 1), detailed geographic data were not available for the MB sample; diversity shown here is for the entire sample.