Identification and Classification of Fungal GPCR Gene Families

Area of Science:

• Mycology
• Biochemistry
• Genomics

Background:

• G protein-coupled receptors (GPCRs) are vital transmembrane proteins for eukaryotic signal transduction.
• Previous studies identified 14 fungal GPCR types and 3 mammalian homologs, but their distribution was unexamined.
• A unified classification of fungal GPCRs was lacking.

Purpose of the Study:

• To establish a comprehensive, unified classification of fungal GPCRs.
• To analyze the distribution and evolutionary patterns of GPCRs across fungal species.
• To identify novel fungal GPCR candidates and predict their functions.

Main Methods:

• Integrated 14 fungal and 3 mammalian GPCR groups into a unified classification system.
• Classified 28,294 GPCRs from 1357 fungal species.
• Employed a custom convolutional neural network (CNN) for novel GPCR identification and AlphaFold Multimer for interaction prediction.

Main Results:

• Established a unified classification of 17 GPCR classes in fungi, significantly expanding the known repertoire.
• Revealed distinct distribution patterns: mammalian homologs prevalent in Early Diverging Fungi (EDF), while other classes dominate Ascomycota and Basidiomycota.
• Identified Pth11-like GPCRs as the most abundant class in Pezizomycotina, linked to fungal pathogenicity, with evidence of lineage-specific reductions.
• Discovered putative novel fungal GPCRs using CNN, with predicted functional relevance through G-alpha protein interactions.

Conclusions:

• Defined the first large-scale, unified classification of fungal GPCRs.
• Uncovered lineage-specific expansions and contractions in fungal GPCR repertoires.
• Identified novel GPCR candidates with potential roles in fungal signaling, opening new avenues for research.