LAUSR

SignificancePrevious attempts to identify the action of natural selection in the Mycobacterium tuberculosis complex (MTBC) were limited by sample size and averaging across time and lineages. We investigate changes in selective pressures across time for every single gene of the MTBC. We developed a methodology to analyze temporal signals of selection in a large dataset (∼5,000 complete genomes) and showed that 1) almost half of the genes seem to have been under positive selection at some point in time; 2) experimentally confirmed epitopes tend to accumulate more mutations in deeper branches than in external branches; and 3) temporal signals identify genes that were conserved in the past but under positive selection in the present, suggesting ongoing adaptation to the host.