Origin and evolution of fungal HECT ubiquitin ligases.

Ubiquitin ligases (E3s) are basic components of the eukaryotic ubiquitination system. In this work, the emergence and diversification of fungal HECT ubiquitin ligases is described. Phylogenetic and structural data indicate that six HECT subfamilies (RSP5, TOM1, UFD4, HUL4, HUL4A and HUL5) existed in the common ancestor of all fungi. These six subfamilies have evolved very conservatively, with only occasional losses and duplications in particular fungal lineages. However, an early, drastic reduction in the number of HECT genes occurred in microsporidians, in parallel to the reduction of their genomes. A significant correlation between the total number of genes and the number of HECT-encoding genes present in fungi has been observed. However, transitions from unicellularity to multicellularity or vice versa apparently had no effect on the evolution of this family. Likely orthologs or co-orthologs of all fungal HECT genes have been detected in animals. Four genes are deduced to be present in the common ancestor of fungi, animals and plants. Protein-protein interactions detected in both the yeast Saccharomyces cerevisiae and humans suggest that some ancient functions of HECT proteins have been conserved since the animals/fungi split.