The metabolic domestication syndrome of budding yeast

Cellular metabolism evolves through changes in the structure and quantitative of metabolic networks. Here, we explore the evolutionary dynamics of metabolic by focusing on the collection of metabolite levels, the metabolome, which captures aspects of cellular physiology. Using a phylogenetic framework, we profiled metabolites in 27 populations of nine budding yeast species, providing a graduated view of bolic variation across multiple evolutionary time scales. Metabolite levels evolve rapidly and independently of changes in the metabolic network's structure, providing complementary information to enzyme repertoire. Although metabolome variation mulates mainly gradually over time, it is profoundly affected by domestication. found pervasive signatures of convergent evolution in the metabolomes of independently domesticated clades of Saccharomyces cerevisiae. Such recurring metabolite differences between wild and domesticated populations affect a substantial part of the metabolome, including rewiring of the TCA cycle and several amino acids that influence production, likely reflecting adaptation to human niches. Overall, our work previously unrecognized diversity in central metabolism and the pervasive influence human- driven selection on metabolite levels in yeasts.