The evolution and function of fish TRIM E3 ubiquitin ligases

FishTRIM aims to study the evolution and function of the TRIM family of E3 ubiquitin ligases in fish.

This family has undergone several clade-specific expansions across the fish phylogeny, with single-copy mammalian TRIMs frequently present in large numbers in fish genomes.

TRIM E3 ligases and their direct interactions with viral proteins are key in host-pathogen relationships, and several fish TRIMs have been associated to antiviral responses.

Additionally, positive selection has been observed in fish TRIM protein domains involved in protein-protein interactions and pathogen recognition.

This suggests that this family of fish E3 ubiquitin ligases may act as an immune mechanism against specific viral pathogens, and therefore the repeated independent expansions of the TRIM repertoire in fish could be the result of an arms race between fish and viruses.

To address these questions, FishTRIM will focus on understanding the function of this family in fish, and their potential co-evolutionary interactions with viruses.

Recent advances in the fields of functional genetics and genomics, such as single-cell technologies and genome editing, allow us to interrogate gene function at unprecedented scale and resolution.

Nonetheless, a phylogenomic approach will be fundamental to determine potential functional overlap across independent expansions, and selection patterns in the context of TRIM protein domains will contribute to illuminate the function of the expanded TRIM repertoire.

FishTRIM aims to deliver frontier knowledge on the biological significance of the different fish TRIM expansions, with potential to revolutionise our understanding of fish immune systems and the evolution of the ubiquitination machinery.

FishTRIM will also explore the role of TRIMs in resistance to viral diseases in fish, with potential transformative outcomes leading to improved fish welfare and food security.