Eco-evolutionary hysteresis in bacterial genomes driven by horizontal gene transfer

Many naturally-occurring bacteria lead a lifestyle of metabolic dependency, i.e. they depend on others for crucial resources. We do not understand what factors drive bacteria towards this lifestyle, and how. Here, we systematically explain the role of horizontal gene transfer (HGT) in metabolic dependency evolution. Across 835 bacterial species, we mapped gene dynamics on a deep evolutionary tree, and assessed the impact of HGT and gene loss on bacterial metabolic networks. Our analyses suggest that genes acquired by HGT can affect which genes are later lost. Dependency evolution by gene loss is contingent on earlier HGT via two steps. First, we find that HGT and gene loss act on contrasting regions of metabolic networks—losses remove existing anabolic routes; HGT adds new catabolic routes. This increases the chance of new metabolic interactions between bacteria, which is a prerequisite for dependency evolution. Second, we show how gaining new routes can promote the loss of specific ancestral routes (termed "eco-evolutionary hysteresis", EEH). Phylogenetic patterns indicate that both types of dependencies—those mediated by EEH and pure gene loss—are equally likely. Our results highlight HGT as an important driver of metabolic dependency evolution in bacteria.