Biology subjects

Martinez-Ugalde, I.

Publications and source records attributed to Martinez-Ugalde, I..

3 recordsLinked to original sources

bioRxiv2025

Comparative transcriptomics reveals an extracellular worm argonaute as an ancestral regulator of LTR retrotransposons.

Safeguarding the genome from non-self elements is essential for reproduction, development, and ageing. One of the major threats to genome integrity is Transposable Elements (TEs), which can be post-transcriptionally silenced through small RNAs (sRNAs) and argonaute proteins. Recent work suggests TE-derived sRNAs may also act as virulence factors in host-pathogen interactions. During infection, the intestinal parasite Heligmosomoides bakeri secretes a single argonaute protein (exWAGO) and a wide variety of TE-derived sRNAs. Although exWAGO is highly expressed, conserved, and secreted by parasitic nematodes, its function and sRNA guide preference remain unclear. Using comparative transcriptomics of the sRNAs bound to exWAGO within parasites of rodents, livestock and humans, and its orthologs in C. elegans, we found that exWAGO is capable of loading sRNAs produced from all classes of TEs in addition to some protein-coding and non-coding transcripts. However, our results suggest that the ancestral endogenous function of exWAGO was likely linked to LTR retrotransposon regulation. To understand how this relates to potential extracellular functions of exWAGO we also examined the sRNAs bound to exWAGO secreted by H. bakeri in both vesicular and non-vesicular forms. Extracellular exWAGO preferentially loads sRNA guides derived from non-autonomous and fragmented LTRs, suggesting the existence of adaptable reservoirs of regulatory sRNAs with potential roles in cross-species RNA communication. Together, our results show that exWAGO is part of an evolutionarily conserved pathway for LTR retrotransposon regulation, while preferentially utilising degenerated elements as sources of secreted sRNAs.

genomics↗

bioRxiv2025

A non-vesicular Argonaute protein is transmitted from nematode to mouse and is important for parasite survival

Argonautes are ancient proteins with well-characterised functions in cell-autonomous gene regulation and genome defense but less clear roles in non-cell-autonomous processes. Extracellular Argonautes have been reported across plants, animals and protozoa yet their biochemical and functional properties remain elusive. Here we demonstrate that an extracellular Argonaute (exWAGO) released by the rodent-infective parasitic nematode Heligmosomoides bakeri is detectable inside mouse cells during the natural infection. We further show that exWAGO is released from H.bakeri in both vesicular and non-vesicular forms that have different resistances to proteolysis, different accessibilities to antibodies and associate with different subsets of secondary siRNAs. Using recombinant exWAGO protein we demonstrate that non-vesicular exWAGO is directly internalised by mouse cells in vitro and that immunisation of mice with exWAGO confers partial protection against subsequent H. bakeri infection and generates antibodies that block exWAGO uptake into cells. Finally, we show that properties of exWAGO are conserved across Clade V nematodes that infect humans and livestock. Together this work expands the context in which Argonautes function and illuminates an RNA-binding protein as a vaccine target for parasitic nematodes.

molecular biology↗

bioRxiv2023

Ancient diversity in host-parasite interaction genes in a model parasitic nematode

Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to increased fitness of rare alleles, resulting in negative frequency-dependent selection, a form of balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Despite their economic and ecological importance, there is limited evidence for balancing selection in parasitism-relevant genes in parasitic nematodes. Here, we sequenced the genomes of several individuals of Heligmosomoides bakeri, a parasite of house mice that is a well-established model parasitic nematode, and Heligmosomoides polygyrus, a closely related parasite of wood mice. We combined our single nematode genome assemblies with chromatin conformation capture (Hi-C) libraries derived from pools of individuals to generate chromosome-level reference genomes for both species. Although H. bakeri is commonly referred to as H. polygyrus in the literature, their genomes show levels of divergence that are consistent with millions of years of independent evolution. We found that the H. bakeri genome, which we expected to be highly homozygous through inbreeding, contained hundreds of hyper-divergent haplotypes, similar to those recently reported in free-living nematodes. Within these haplotypes, we found an enrichment of protein families that interact with the host immune response, including protease inhibitors and transthyretin-related proteins. We also found that many of these haplotypes originated prior to the divergence between H. bakeri and H. polygyrus, suggesting that they have been maintained since the last common ancestor of the two species by long-term balancing selection. Together, our results suggest that selection pressures exerted on parasites by their hosts have led to unexpected modes and levels of genetic diversity in the genomes of these economically and ecologically important species.

evolutionary biology↗