Journal Article

Human genetic ancestry, Mycobacterium tuberculosis diversity, and tuberculosis disease severity in Dar es Salaam, Tanzania

Xu, Zhi Ming, Borrell, Sonia, Reither, Klaus, Ross, Amanda, Fellay, Jacques, Hella, Jerry, Gagneux, Sebastien, Quintana-Murci, Lluis, Zwyer, Michaela, Sasamalo, Mohamed, Hiza, Hellen Charles, Rutaihwa, Liliana K, Rotival, Maxime, Brites, Daniela, Portevin, Damien

2026

Overview

Infectious diseases have affected humanity for millennia and are among the strongest selective forces. Tuberculosis (TB) is an ancient disease, caused by the human-adapted members of the Mycobacterium tuberculosis complex (MTBC). The outcome of TB infection and disease is highly variable, and co-evolution between human populations and MTBC strains may account for some of this variability. Particular human genetic ancestries have been associated with higher susceptibility to TB, but sociodemographic aspects of the disease can confound such associations. Here, we studied 1000 TB patients from Dar es Salaam, Tanzania, together with their respective MTBC isolates, by combining human and bacterial genomics with clinical data. We found that the genetic background of the TB patient population was strongly influenced by migrations of Bantu-speaking populations from West Africa, which contrasts with the corresponding MTBC genotypes that were mainly introduced from outside Africa. These findings suggest a recent evolutionary history of co-existence between the human and MTBC populations in Dar es Salaam. We detected no evidence of an effect of human genetic ancestry, or MTBC phylogenetic diversity alone, nor their interaction, on TB disease severity. There was also no evidence of an association between human variation genome-wide and TB disease severity. Treatment-seeking, social, and environmental factors are likely to be the main determinants of disease severity at the point of care in this patient population.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Adult / ancestry / Coevolution / disease severity / Environmental factors / Ethnicity / Evolutionary Biology / Female / Genetic diversity / Genetic variability / Genetic Variation / Genotype / Genotypes / HIV / host–pathogen co-evolution / host–pathogen interactions / Human immunodeficiency virus / Humans / Hypotheses / Infectious diseases / Male / Microbiology and Infectious Disease / Middle Aged / Mycobacterium tuberculosis / Mycobacterium tuberculosis - classification / Mycobacterium tuberculosis - genetics / Mycobacterium tuberculosis - isolation & purification / Patients / Phylogenetics / Phylogeny / Population / Severity of Illness Index / Tanzania - epidemiology / Tuberculosis / Tuberculosis - epidemiology / Tuberculosis - genetics / Tuberculosis - microbiology / Tuberculosis - pathology / Young Adult