Global analysis of the genetic and epigenetic contributions to phenotypic plasticity in a wild yeast strain

The natural M28 Saccharomyces cerevisiae strain, isolated from damaged grapes in Montalcino area (Tuscany), showed a fascinating 2:2 segregation of two unlinked loci: the recessive resistance to a toxic analogue of leucine (5’5’5 trifloroleucine, TFL) and the morphotype. Two of the four M28 meiotic products (spores) in fact grow as smooth colonies while the other two exhibit complex structured filigreed colonies. In this work, preliminary phenotypic investigations demonstrated the uniqueness of the M28 system since the four meiotic products displayed a remarkable phenotypic variability concerning the ability to generate pseudohyphal structures or to invade solid substrates. Additionally, we showed that each spore is able to spontaneously and reversibly switch between the two described morphotypes at high frequencies. Seduced by this puzzling system where Mendelian and Lamarckian theories seems to be reconciled we started a global investigation of the genetic, proteomic and chromatin profiles across the four spores. Using cutting-edge mass spectrometry and sequencing technologies we obtained the following results: i) we confirmed the genetic determinant of the TFL-phenotype additionally illustrating how this loss of function can massively reshape the amino acid metabolism through the alteration of chromatin accessibility via histone modifications (trimethylation of lysine 4 of histone H3 and acetylation of histone H4); ii) we demonstrated there are no genetic polymorphisms segregating with the morphotype but rather we identified few epialleles segregating 2:2 with the morphotype; iii) for the first time we showed the extensive epigenome variability among four meiotic products of a natural S. cerevisiae strain; iv) we found structural protein rearrangements in several prion-like proteins during the dimorphic transition from filigreed to smooth and vice-versa and showed that for Hrp1 protein this switch is accompanied by a significant change in the number of cells per population bearing the Hrp1p-aggregate. These results evidenced that both genetic and epigenetic contributions are affecting the phenotypic plasticity in the M28 system proposing an update of the “genome renewal” theory that introduces chromatin reshaping as a rapid adaptive mechanism allowing the appearance of new stable and potentially advantageous traits in the progeny of diploid strains.