Functional and evolutionary integration of a fungal gene with a bacterial operon

Abstract

AbstractSiderophores are crucial for iron-scavenging in microorganisms. While many yeasts can uptake siderophores produced by other organisms, they are typically unable to synthesize siderophores themselves. In contrast,Wickerhamiella/Starmerella(W/S) clade yeasts gained the capacity to make the siderophore enterobactin following the remarkable horizontal acquisition of a bacterial operon enabling enterobactin synthesis. Yet, how these yeasts absorb the iron bound by enterobactin remains unresolved. Here, we demonstrate that Enb1 is the key enterobactin importer in the W/S-clade speciesStarmerella bombicola. Through phylogenomic analyses, we show thatENB1is present in all W/S clade yeast species that retained theenterobactin biosynthetic genes. Conversely, it is absent in species that lost theentgenes, except forStarmerella stellata, making this species the only cheater in the W/S clade that can utilize enterobactin without producing it. Through phylogenetic analyses, we infer thatENB1is a fungal gene that likely existed in the W/S clade prior to the acquisition of theentgenes and subsequently experienced multiple gene losses and duplications. Through phylogenetic topology tests, we show thatENB1likely underwent horizontal gene transfer from an ancient W/S clade yeast to the order Saccharomycetales, which includes the model yeastSaccharomyces cerevisiae, followed by extensive secondary losses. Taken together, these results suggest that the fungalENB1and bacterialentgenes were cooperatively integrated into a functional unit within the W/S clade that enabled adaptation to iron-limited environments. This integrated fungal-bacterial circuit and its dynamic evolution determines the extant distribution of yeast enterobactin producers and cheaters.