Co-evolutionary dynamics of defense systems and anti-defense genes in chromosomes and mobile genetic elements of Enterobacteriaceae

Bacterial defense systems undergo rapid evolutionary changes, yet the specific contributions of the genomic compartment (chromosomal versus mobile genetic element [MGE]) to these dynamics remain unclear. We analyzed 6,907 genomes from 213 species of Enterobacteriaceae using a phylogenetic birth-death model to quantify gain, loss, expansion, and reduction of defense (DEF) and anti-defense (anti-DEF) gene families. We found that DEF turnover differs from the background dynamics of the genomic elements that carry them. Direct comparisons among DEFs further revealed differences in loss and copy-number dynamics across genomic compartments, with the highest rates on chromosomes, intermediate rates on plasmids and ICEs/IMEs, and the lowest rates on prophages, whereas the relative balance between gain and loss and between expansion and reduction remained similar across chromosomes and MGEs. MGE-associated anti-DEFs showed higher loss, expansion, and reduction rates than DEFs, whereas chromosome-associated anti-DEFs showed lower gain rates than DEFs. Finally, we found that gains and losses of DEFs and anti-DEFs were positively correlated across bacterial lineages, with positive associations observed for both matching (that is, antagonistic) and non-matching pairs. Together, these results show that genomic background affects the overall flux of DEFs and anti-DEFs, and that turnover of DEFs and anti-DEFs is evolutionarily coupled across lineages.