Cross-species evolutionary rewiring in the enteric bacterium Campylobacter

The lateral transfer of genes among bacterial strains and species has opposing effects, conferring potentially beneficial adaptations whilst introducing disharmony in coadapted genomes. The prevailing outcome will depend upon the fitness cost of disrupting established epistatic interactions between genes. It is challenging to understand this in nature because it requires population-scale analysis of recombination and genomic coadaptation, and laboratory confirmation of the functional significance of genotype variation. By assigning the ancestry of DNA in the genomes of two species of the world’s most common enteric bacterial pathogen, we show that up to 28% of the Campylobacter coli genome has been recently introgressed from Campylobacter jejuni . Then, by quantifying covariation across the genome we show that >83% of putative epistatic links are between introgressed C. jejuni genes in divergent genomic positions (>20kb apart), consistent with independent acquisition. Much of this covariation is between 16 genes, with just 5 genes accounting for 99% of epistatic SNP pairs. Laboratory mutagenesis and complementation cloning assays demonstrated functional links between these genes, specifically related to formate dehydrogenase (FDH) activity. These findings suggest that the genetic confederations that define genomic species may be transient. Even for complex traits such as central metabolism in the bacterial cell, conditions can arise where epistatic genes can be decoupled, transferred and reinstated in a new genetic background. ### Competing Interest Statement The authors have declared no competing interest.