Journal Article > ResearchFull Text
Nat Genet. 2016 October 31; Volume 48 (Issue 12); 1535-1543.; DOI: 10.1038/ng.3704
Stucki D, Brites D, Jeljeli L, Coscolla M, Liu Q, et al.
Nat Genet. 2016 October 31; Volume 48 (Issue 12); 1535-1543.; DOI: 10.1038/ng.3704
Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
Journal Article > ResearchAbstract
Nat Genet. 2015 January 19; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, et al.
Nat Genet. 2015 January 19; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.