Pan-genome analysis ofMycobacterium africanum: insights to dynamics and evolution

Mycobacterium tuberculosis complex (MTBC) consists of seven major lineages with three of them reported to circulate within West Africa: lineage 5 (West African 1) and lineage 6 (West African 2) which are geographically restricted to West Africa and lineage 4 (Euro-American lineage) which is found globally. It is unclear why the West African lineages are not found elsewhere; some hypotheses suggest that it could either be harboured by an animal reservoir which is restricted to West Africa, or strain preference for hosts of West African ethnicity, or inability to compete with other lineages in other locations. We tested the hypothesis that M. africanum (MAF) might have emigrated out of West Africa but was outcompeted by more virulent strains of M. tuberculosis (MTB). Whole genome sequences of MTB from Nigeria (n=21), China (n=21) and MAF from Mali (n=24) were retrieved, and a pan-genome analysis was performed after fully annotating these genomes. The outcome of this analysis shows that Lineages 4, 5 and 6 have relatively close pan-genomes whilst lineage 2 has an open pan-genome. We also see a correlation in numbers of some multiple copy core genes and amino acid substitution with lineage specificity that may have contributed to geographical distribution of these lineages. The findings in this study provides a perspective to one of the hypotheses that M. africanum might find it difficult to compete against the more modern lineages outside West Africa hence its localization to the geographical region.