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While most bacteria undergo lateral gene transfer, including other mycobacteria, M. tuberculosis evolves clonally. Most methods to detect positive selection were developed for eukaryotic, sexual species. To understand the effect of positive selection on patterns of diversity in a clonally evolving population, I examined drug resistance associated loci in natural populations of M. tb with both susceptible and resistant isolates. I found that resistance loci can be characterized by either diversifying selection with numerous rare variants present in the population or selection for a specific variant. We hypothesize that this difference is related to fitness costs associated with resistance mutations. I was able to capture known resistance determinants using measures of nucleotide diversity and population differentiation combined with identification of homoplastic sites, and I identified several novel loci with patterns of diversity similar to known loci, suggesting these genes are affected by positive selection and possibly involved in drug resistance.

This work has published in mSystems here!