Evaluating the contributions of purifying selection and progeny-skew in dictating within-host Mycobacterium tuberculosis evolution

The within-host evolutionary dynamics of TB remain unclear, and underlying biological characteristics render standard population genetic approaches based upon the Wright-Fisher model largely inappropriate. In addition, the compact genome combined with an absence of recombination is expected to result in strong purifying selection effects. Thus, it is imperative to establish a biologically-relevant evolutionary framework incorporating these factors in order to enable an accurate study of this important human pathogen. Further, such a model is critical for inferring fundamental evolutionary parameters related to patient treatment, including mutation rates and the severity of infection bottlenecks. We here implement such a model and infer the underlying evolutionary parameters governing within-patient evolutionary dynamics. Results demonstrate that the progeny skew associated with the clonal nature of TB severely reduces genetic diversity and that the neglect of this parameter in previous ...