Genome-wide evolutionary shifts shape the emergence of dominant circulating clones in Mycobacterium abscessus

Mycobacterium abscessus (Mab) infections have been linked to the rise of dominant circulating clones (DCCs), but the evolutionary factors contributing to their formation are not well understood. Researchers analyzed 11,314 Mab genomes from around the world to study genome-wide changes during the emergence of seven DCCs. To ensure accurate evolutionary inferences, they established a robust core-genome analytical framework that accounts for gene conservation on a population-wide scale and validates individual genome reads.

Based on this framework, they identified a stable core genome of 3,001 genes as the minimum common set across the currently sequenced Mab populations. Analyzing the core genome showed a significant decrease in recombination relative to mutation following the expansion of DCCs. This shift suggests a predominant mutation-driven clonal evolution.

In addition to changes in recombinational processes, selective pressures also shifted during this transition. Of the 29 genes that shifted from purifying to positive selection, these genes continued to adapt during DCC expansion. On the other hand, 19 genes demonstrated the opposite pattern, indicating increased functional constraint after clonal establishment.

While the specific accessory genes acquired varied among the DCCs, gains consistently outweighed losses during DCC formation. These gains were found to display functional convergence in areas such as environmental sensing, metabolism, metal homeostasis, and stress responses.

In summary, this study highlights consistent evolutionary shifts across independently emerged DCCs of Mab. These shifts primarily occur in evolutionary processes and adaptive functions, rather than through a single shared genetic determinant.