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

Abstract

Mycobacterium abscessus exhibits extensive genomic diversity, yet independently emerged dominant circulating clones (DCCs) have achieved widespread distribution. However, the evolutionary changes associated with their emergence and subsequent diversification remain poorly understood. Here, we analyzed 11,314 genomes from 30 countries using a conservative framework integrating population-wide validation and read-supported sequence reconstruction, defining a stable core genome of 3,001 genes. Across seven DCCs, accessory-gene gains consistently exceeded losses on the ancestral branches leading to clone formation, with recurrent functions involving metal homeostasis, metabolism, environmental sensing and stress responses. Recombination also contributed substantial variation in specific lineages; in DCC3, ancestral recombinant regions encompassed core genes involved in iron acquisition, respiratory metabolism and protein homeostasis. Following DCC establishment, the relative contribution of homologous recombination to mutation consistently declined during within-clone diversification, indicating a broad shift toward mutation-dominated core-genome evolution. Together, these findings suggest a recurring pattern in DCC evolution, with accessory-genome gain and lineage-specific recombination occurring during clone formation, followed by increasingly mutation-dominated diversification after establishment.