Population genomics of Mycobacterium tuberculosis in the Inuit.
Nunavik, Québec suffers from epidemic tuberculosis (TB), with an incidence 50-fold higher than the Canadian average. Molecular studies in this region have documented limited bacterial genetic diversity among Mycobacterium tuberculosis isolates, consistent with a founder strain and/or ongoing spread. We have used whole-genome sequencing on 163 M. tuberculosis isolates from 11 geographically isolated villages to provide a high-resolution portrait of bacterial genetic diversity in this setting. All isolates were lineage 4 (Euro-American), with two sublineages present (major, n = 153; minor, n = 10). Among major sublineage isolates, there was a median of 46 pairwise single-nucleotide polymorphisms (SNPs), and the most recent common ancestor (MRCA) was in the early 20th century. Pairs of isolates within a village had significantly fewer SNPs than pairs from different villages (median: 6 vs. 47, P < 0.00005), indicating that most transmission occurs within villages. There was an excess of nonsynonymous SNPs after the diversification of M. tuberculosis within Nunavik: The ratio of nonsynonymous to synonymous substitution rates (dN/dS) was 0.534 before the MRCA but 0.777 subsequently (P = 0.010). Nonsynonymous SNPs were detected across all gene categories, arguing against positive selection and toward genetic drift with relaxation of purifying selection. Supporting the latter possibility, 28 genes were partially or completely deleted since the MRCA, including genes previously reported to be essential for M. tuberculosis growth. Our findings indicate that the epidemiologic success of M. tuberculosis in this region is more likely due to an environment conducive to TB transmission than a particularly well-adapted strain.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada, H3A 1A2; The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada, H4A 3J1;
Robyn S
RS
Lee
The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada, H4A 3J1;
Nicolas
N
Radomski
Nunavik Regional Board of Health and Social Services, Kuujjuaq, QC, Canada, J0M 1C0;
Jean-Francois
JF
Proulx
Département de Sciences Biologiques, Université de Montréal, Montreal, QC, Canada, H2V 2S9;
Ines
I
Levade
Département de Sciences Biologiques, Université de Montréal, Montreal, QC, Canada, H2V 2S9;
B Jesse
BJ
Shapiro
The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada, H4A 3J1;
Fiona
F
McIntosh
Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada, H9X 3R5;
Hafid
H
Soualhine
The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada, H4A 3J1.
Dick
D
Menzies
The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; marcel.behr@mcgill.ca.
Marcel A
MA
Behr
D005798:Genes, Bacterial; D005828:Genetics, Population; D006801:Humans; D004930:Inuit; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011792:Quebec / Q000453:epidemiology; D012641:Selection, Genetic; D014376:Tuberculosis / Q000453:epidemiology / Q000635:transmission
Mycobacterium tuberculosis; evolution; whole-genome sequencing