BackgroundHorizontal gene transfer (HGT) is an evolutionary mechanism of adaptive importance, which has been deeply studied in wineS. cerevisiaestrains, where those acquired genes conferred improved traits related to both transport and metabolism of the nutrients present in the grape must. However, little is known about HGT events that occurred in wildSaccharomycesyeasts and how they determine their phenotypes.ResultsThrough a comparative genomic approach amongSaccharomycesspecies, we detected a subtelomeric segment present in theS. uvarum,S. kudriavzevii, andS. eubayanusspecies, belonging to the first species to diverge in theSaccharomycesgenus, but absent in the otherSaccharomycesspecies. The segment contains three genes, two of which were characterized, namedDGD1andDGD2.DGD1encodes dialkylglicine decarboxylase, whose specific substrate is the non-proteinogenic amino acid 2-aminoisobutyric acid (AIB), a rare amino acid present in some antimicrobial peptides of fungal origin.DGD2encodes putative zinc finger transcription factor, which is essential to induce the AIB-dependent expression ofDGD1. Phylogenetic analysis showed thatDGD1andDGD2are closely related to two adjacent genes present inZygosaccharomyces.ConclusionsThe presented results show evidence of an early HGT event conferring new traits to the ancestor of theSaccharomycesgenus that could be lost in the evolutionary more recentSaccharomycesspecies, perhaps due to loss of function during the colonization of new habitats.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12915-023-01566-6.