Identification and Classification of Fungal GPCR Gene Families

Abstract

G protein-coupled receptors (GPCRs) are transmembrane proteins crucial for signal transduction in eukaryotes, responding to diverse extracellular signals. Researchers have found 14 distinct types of GPCRs in fungi, but their distribution among numerous fungal species has remained largely unexamined. Our study identified and classified GPCRs in 1,357 fungal species and shed light on their distribution in fungi. The predominant class detected in fungi was Pth11-like GPCRs, exclusively found in Pezizomycotina and notably recognized for their involvement in fungal pathogenicity. Our analysis suggested that the Pezizomycotina ancestor possessed a more extensive array of Pth11-like GPCRs, but over time, some species experienced considerable reductions in these GPCRs in conjunction with genome contractions. Additionally, we identified 2,089 mammalian homologs in the Rhodopsin, Glutamate, and Frizzled classes across 594 fungal species, thereby augmenting the recognized fungal GPCR classes by including three classes previously thought to be mammalian-specific. Utilizing a custom-built convolutional neural network (CNN) for the identification of fungal GPCRs, we discovered several potential novel fungal GPCRs. Moreover, predicted interactions between these prospective new GPCRs and G-alpha proteins, as simulated by AlphaFold Multimer, provided further validation for these findings.