Fungi represent one of the most important kingdoms with a large diversity of complexity levels (from unicellular yeasts to complex multicellular mushrooms), lifestyles and nutritional modes, and include some of the most devastating plant and animal pathogens. Sensing environmental cues is a key process in multicellular organisms (e.g. for cell-cell communication), and as such its sophistication has been instrumental in the evolution of multicellularity. While there is evidence for the expansion of cell surface receptor families in most multicellular lineages, known receptor families show no signs of expansion in multicellular fungi. This suggests that the evolution of multicellularity in fungi either did not follow this principle or that hitherto undiscovered receptor families should exist. This predisposition and preliminary comparative genomic data led us to a systematic inventory of 7-transmembrane domain proteins with a GPCR-like architecture in the fungal kingdom. Analysis of >400 complete fungal genomes revealed 0 to 537 (mean 82) GPCR-like proteins that lack clear GPCR domain signatures but show some homology to canonical GPCR genes, considered hereafter as putative G-protein coupled receptors (pGPCR). We investigate the function of identified pGPCRs in multicellular development and fungal pathogenicity by mining transcriptomic data, gene knockouts and biochemical assays. Tests of the correlation between cellular complexity and pGPCR repertoires suggest functional links between multicellularity in several fungal groups. There are 5-10 times more pGPCRs than canonical GPCRs in fungal genomes, providing a large pool of uncharacterized fungal proteins that may also be key targets in the development of antifungal drugs.
Pázmány Péter Catholic University, Esztergom, Hungary