Epistasis, core-genome disharmony, and adaptation in recombining bacteria

Aidan J. Taylor, Koji Yahara, Ben Pascoe, Seungwon Ko, Leonardos Mageiros, Evangelos Mourkas, Jessica K. Calland, Santeri Puranen, Matthew D. Hitchings, Keith A. Jolley, Carolin M. Kobras, Sion Bayliss, Nicola J. Williams, Arnoud H. M. van Vliet, Julian Parkhill, Martin C. J. Maiden, Jukka Corander, Laurence D. Hurst, Daniel Falush, Paul Keim, Xavier Didelot, David J. Kelly, Samuel K. Sheppard

Recombination of short DNA fragments via horizontal gene transfer (HGT) can introduce beneficial alleles, create genomic disharmony through negative epistasis, and create adaptive gene combinations through positive epistasis. For non-core (accessory) genes, the negative epistatic cost is likely to be minimal because the incoming genes have not co-evolved with the recipient genome and are frequently observed as tightly linked cassettes with major effects. By contrast, interspecific recombination in the core genome is expected to be rare because disruptive allelic replacement is likely to introduce negative epistasis. Why then is homologous recombination common in the core of bacterial genomes? To understand this enigma, we take advantage of an exceptional model system, the common enteric pathogens Campylobacter jejuni and C. coli that are known for very high magnitude interspecies gene flow in the core genome. As expected, HGT does indeed disrupt co-adapted allele pairings, indirect evidence of negative epistasis. However, multiple HGT events enable recovery of the genome's co-adaption between introgressing alleles, even in core metabolism genes (e.g., formate dehydrogenase). These findings demonstrate that, even for complex traits, genetic coalitions can be decoupled, transferred, and independently reinstated in a new genetic background-facilitating transition between fitness peaks. mBio. April 2024

KmerAperture: Retaining k-mer synteny for alignment-free extraction of core and accessory differences between bacterial genomes

Matthew P. Moore, Mirjam Laager,Paolo Ribeca, Xavier Didelot

By decomposing genome sequences into k-mers, it is possible to estimate genome differences without alignment. Techniques such as k-mer minimisers, for example MinHash, have been developed and are often accurate approximations of distances based on full k-mer sets. These and other alignment-free methods avoid the large temporal and computational expense of alignment. However, these k-mer set comparisons are not entirely accurate within-species and can be completely inaccurate within-lineage. This is due, in part, to their inability to distinguish core polymorphism from accessory differences. Here we present a new approach, KmerAperture, which uses information on the k-mer relative genomic positions to determine the type of polymorphism causing differences in k-mer presence and absence between pairs of genomes. We show that KmerAperture can accurately distinguish both core and accessory sequence diversity without alignment, outperforming other k-mer based tools.

PLos Genetics.; April 2024