Genetic dominance governs the evolution and spread of mobile genetic elements in bacteria

Abstract

14 Mobile genetic elements (MGEs), such as plasmids, promote bacterial evolution 15 through horizontal gene transfer (HGT). However, the rules governing the repertoire 16 of traits encoded on MGEs remain unclear. In this study, we uncovered the central 17 role of genetic dominance shaping genetic cargo in MGEs, using antibiotic resistance 18 as a model system. MGEs are typically present in more than one copy per host 19 bacterium and, as a consequence, genetic dominance favors the fixation of dominant 20 mutations over recessive ones. Moreover, genetic dominance also determines the 21 phenotypic effects of horizontally acquired MGE-encoded genes, silencing recessive 22 alleles if the recipient bacterium already carries a wild-type copy of the gene. The 23 combination of these two effects governs the catalogue of genes encoded on MGEs, 24 dictating bacterial evolution through HGT.25

Evolutionary Pathways and Trajectories in Antibiotic Resistance

“…When new mutations appear in multicopy plasmids, the mutations coexist with their ancestral allele during a number of generations that are proportional to the plasmid copy number. This coexistence allows plasmids to provide simultaneous resistance to different antibiotics of the same family, overcoming the restraints imposed by tradeoffs in the evolution of antimicrobial resistance genes (258). These features highlight multicopy plasmids as important catalysts of bacterial evolution.…”

“…Polyploidy derived from multiple replication forks might produce a phenotypic delay of a recessive, antibiotic-resistance mutation that remains undetectable during the next 3-4 generations (256,257). This is particularly the case for plasmid recessive mutations, because plasmids can be regarded as stable polyploid DNA molecules (258). In any case, our current ability to detect rare mutations in the global sequence space that potentially provide antibiotic resistance is probably low.…”

Evolutionary mechanisms that determine which bacterial genes are carried on plasmids

“…Rodríguez-Beltrán et al [44] have recently shown that polyploidy (i.e. gene copies being present on both mobile element and chromosome or, for multi-copy plasmids, on multiple plasmids) plays an important, and thus far neglected, role in mobile genetic element evolution: polyploidy masks the e↵ect of recessive mutations on mobile genetic elements ('genetic dominance'), and thus mobile genetic elements are primarily associated with dominant mutations.…”

Increased copy number couples the evolution of plasmid horizontal transmission and antibiotic resistance

“…However, high PCN can also limit evolvability because it affects both genetic drift and selection acting on plasmid mutations 34 . Selection will further depend on the genetic dominance of plasmid alleles 35 . copA* variants might differ in all these aspects, as they will have high PCN but also experience frequent bottlenecks due to conjugation.…”