Mycobacterium abscessus (Mab) infections are increasingly associated with dominant circulating clones (DCCs), yet the evolutionary processes underlying their emergence remain poorly understood. Here, we analyzed 11,314 globally collected Mab genomes to investigate genome-wide evolutionary changes during the emergence of seven DCCs. We established a conservative core-genome analytical framework that integrates population-wide gene conservation with read-level validation to minimize the influence of assembly-derived variation on downstream evolutionary inference. Applying this framework to the global Mab population, we defined a stable core genome of 3,001 genes, representing a conservative lower bound across currently sequenced Mab populations. Core-genome analysis revealed a substantial decline in recombination relative to mutation following DCC expansion, indicating a broad shift towards mutation-dominated clonal evolution. Selective pressures also changed across this transition: 29 genes shifted from purifying to positive selection, consistent with continued adaptation during DCC expansion, whereas 19 showed the opposite pattern, suggesting increased functional constraint after clonal establishment. Although the accessory genes acquired differed among DCCs, gains consistently exceeded losses during DCC formation and showed functional convergence in environmental sensing, metabolism, metal homeostasis and stress responses. Together, these findings reveal consistent evolutionary shifts across independently emerged DCCs, with convergence occurring primarily in evolutionary processes and adaptive functions rather than through a single shared genetic determinant.
Zhu, C., Zhou, Y., Ni, M., Huang, Z., Wang, Z., Li, W.
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