Metabolic adaptations underlying genome flexibility in prokaryotes

Even across genomes of the same species, prokaryotes exhibit remarkable flexibility in gene content. We do not know whether this flexible or \"accessory\" content is mostly neutral or adaptive, largely due to the lack of explicit analyses of accessory gene function. Here, across 96 diverse prokaryotic species, I show that a considerable fraction (~40%) of accessory genomes harbours beneficial metabolic functions. These functions take two forms: (1) they significantly expand the biosynthetic potential of individual strains, and (2) they help reduce strain-specific metabolic auxotrophies via intra-species metabolic exchanges. I find that the potential of both these functions increases with increasing genome flexibility. Together, these results are consistent with a significant adaptive role for prokaryotic pangenomes.\n\nAuthor SummaryRecent and rapid advancements in genome sequencing technologies have revealed key insights into the world of bacteria and archaea. One puzzling aspect uncovered by these studies is the following: genomes of the same species can often look very different. Specifically, some \"core\" genes are maintained across all intraspecies genomes, but many \"accessory\" genes differ between strains. A major ongoing debate thus asks: do most of these accessory genes provide a benefit to different strains, and if so, in what form? In this study, I suggest that the answer is \"yes, through metabolic interactions\". I show that many accessory genes provide significant metabolic advantages to different strains in different conditions. I achieve this by explicitly conducting a large-scale systematic analysis of 1,339 genomes across 96 diverse species of bacteria and archaea. A surprising prediction of this study that in many ecological niches, co-occurring strains of the same species may help each other survive by exchanging metabolites exclusively produced by these different accessory genes. More pronounced gene differences lead to more underlying metabolic advantages.