The Architecture of Gene Silencing: Evolutionary Landscapes of Argonaute Proteins and small RNA pathways in Nematoda and Nematomorpha

: (Alternative Format Thesis)

Abstract

RNA interference (RNAi) is an ancient mechanism of gene regulation and genome defence, mediated by the sequence complementarity between a small RNA (sRNA) guide, bound to an Argonaute protein, and its target RNA molecule. Foundational discoveries in RNAi have come from the model nematode Caenorhabditis elegans, yet beyond C. elegans and its close relatives, the diversity of these systems across the broader nematode phylum remains unclear.
Nematoda is a species-rich group with complex life cycles, wide ecological niches, and both free-living and parasitic representatives. Extrapolating knowledge from a single model to such diversity is therefore inappropriate. While the RNAi repertoire of other nematodes is still being uncovered, even less is known about their sister phylum, the Nematomorpha; an exclusively parasitic lineage infecting non-vertebrate hosts and largely unexplored in terms of sRNA biology.
This thesis investigates the evolutionary and functional diversification of Argonaute proteins and their associated sRNA pathways across nematodes and nematomorphs using phylogenetic, comparative genomic, and molecular approaches. Chapter 2 reconstructs Argonaute phylogeny across nematodes, revealing clade-specific expansions and losses that shaped sRNA pathway evolution. Chapter 3 characterises the interactome of SrWAGO1, a worm-exclusive WAGO protein enriched in parasitic female Strongyloides ratti, through combined molecular and computational analyses. Chapter 4 uses orthology and transcriptomic data to define RNAi systems in nematomorphs, providing the first comparative insight into sRNA pathway evolution in this group.
Together, these findings reveal that nematodes and nematomorphs followed distinct evolutionary strategies in shaping their RNAi repertoires, reflecting both adaptive pressures and genomic constraints. By integrating phylogenetic, genomic, and functional analyses, this work establishes a new framework for exploring the evolution of Argonaute proteins and sRNA pathways beyond traditional models and reveals how ancient regulatory systems adapt to diverse lifestyles. These findings advance our understanding of RNAi diversity and provide a foundation for future studies linking Argonaute function, small RNA biology, and genome evolution.

Date of Award	24 Jun 2026
Original language	English
Awarding Institution	University of Bath
Sponsors	UKRI BBSRC
Supervisor	Vicky Hunt (Supervisor) & Laurence Hurst (Supervisor)