The within-host evolutionary dynamics of TB remain unclear, and underlying biological characteristics (including clonality) render standard population genetic approaches based upon the Kingman coalescent largely inappropriate. In addition, the compact genome combined with a lack of recombination is expected to result in strong purifying selection as well as wide-spread background selection effects. This combination of highly skewed progeny distributions and strong constraint, combined with severe infection-related bottlenecks, are all expected to strongly reduce within patient variation. In neglecting these factors, our preliminary analyses suggest that earlier work in TB has greatly under-estimated mutation rates in order to account for these reduced levels of variation. We have carried out an approximate Bayesian (ABC) approach utilizing within-host site frequency spectra in order to disentangle these evolutionary processes, implemented under an alternative coalescent model (the so-called multiple merger coalescent). This framework thus provides novel population genetic insight in to this important human pathogen, and uniquely provides unbiased estimates of key evolutionary parameters via the development of an organism-appropriate null model.

Ana Morales earned her PhD in Archaeology at the University of Calgary, studying ancient mtDNA from Mexico and Central America. As a Center for Evolution & Medicine Research Fellow, she is currently working in the Jensen Lab (and in collaboration with the Stone Lab (ASU)) mainly on the population genetics of time-sampled pathogen data. Other projects involve the study of human past populations' microbiome through dental calculus and recovering ancient pathogens from Central America.