Genetic and environmental determinants of multicellular-like phenotypes in fission yeast

Abstract

Multicellular fungi have repeatedly given rise to primarily unicellular yeast species. Some of these, includingSchizosaccharomyces pombe, are able to revert to multicellular-like phenotypes (MLP). Our bioinformatic analysis of existing data suggested that, besides some regulatory proteins, most proteins involved in MLP formation are not functionally conserved betweenS. pombeand budding yeast. We developed high-throughput assays for two types of MLP inS. pombe: flocculation and surface adhesion, which correlated in minimal medium, suggesting a common mechanism. Using a library of 57 naturalS. pombeisolates, we found MLP formation to widely vary across different nutrient and drug conditions. Next, in a segregantS. pombelibrary generated from an adhesive natural isolate and the standard laboratory strain, MLP formation correlated with expression levels of the transcription-factor genembx2and several flocculins. Quantitative trait locus mapping of MLP formation located a causal frameshift mutation in thesrb11gene encoding cyclin C, a part of the Cdk8 kinase module (CKM) of the Mediator complex. Other CKM deletions also resulted in MLP formation, consistently through upregulation ofmbx2, and only in minimal media. We screened a library of 3721 gene-deletion strains, uncovering additional genes involved in surface adhesion on minimal media. We identified 31 high-confidence hits, including 19 genes that have not been associated with MLPs in fission or budding yeast. Notably, deletion ofsrb11, unlike deletions of the 31 hits, did not compromise cell growth, which might explain its natural occurrence as a QTL for MLP formation.