Exploiting nematode genomes to illuminate parasite biology

Genomic epidemiology is emerging as a valuable tool for informing helminth control strategies. Recent advances in population genomics applied to Fasciola hepatica, Onchocerca volvulus, Wuchereria bancrofti, and Brugia malayi have demonstrated utility in characterising drug resistance loci, estimating reproductive worm burden, assessing treatment response, and elucidating transmission dynamics. In F hepatica, comparative analyses have identified region specific triclabendazole resistance loci, underscoring the need for geographically tailored surveillance. In filarial parasites, genome-wide data from individual microfilariae have enabled the estimation of reproductive worm burden and the differentiation between recrudescence and reinfection, two critical parameters for evaluating treatment efficacy and mass drug administration (MDA) programs that were previously difficult to obtain. Genetic relatedness and population structure analyses have provided further insight into transmission dynamics, revealing parasite movement within and between host populations, across geographic regions, and among host species. These approaches offer a framework for tracking transmission pathways and the spread of epidemiologically important traits such as drug resistance. However, broader implementation and effective integration of genomic tools into control programs will require continued development and coordinated efforts. Although technical advances such as exome capture and whole-genome amplification have significantly improved the recovery of parasite DNA from clinical and field samples, further refinement of methods to obtain parasite genetic data from diverse sample types, such as stool biobanks, blood smears, and vector samples for xenomonitoring, should remain a high priority. In parallel, it is essential to establish curated population genomic databases and standardised, modular analytical pipelines adaptable to varied epidemiological scenarios to support the design of gene panels with informative markers suitable for field-deployable genotyping platforms. Genomic methods when used as a complement to parasitological techniques have the capacity to significantly enhance the precision and effectiveness of helminth control efforts.

Professor Makedonka Mitreva

Washington University School of Medicine, USA

Professor Makedonka Mitreva

Washington University School of Medicine, USA

The HYP genes of plant-parasitic Globodera nematodes encode secreted effector proteins with staggering sequence diversity. Previous work on HYPs strongly suggests that this diversity is allelic and that it is produced by developmentally-programmed rearrangements: that is, the nematodes edit HYP genes in their somatic cells by shuffling a set of short DNA sequence motifs within a hypervariable domain. Although the germline diversity of HYP alleles is small, such editing is thought to create hundred or thousands of distinct somatic alleles across a population. Both the mechanism of HYP editing and its pathogenic function are unknown. In this talk, we discuss a DNA repair hypothesis for the editing mechanism that the nematode uses to rearrange HYP genes, and we evaluate this in light of the latest findings. We also present an immune evasion hypothesis for the pathogenic function of HYP editing, which we discuss in comparison with a range of analogous editing systems in distantly related organisms.

Dr Vincent Hanlon

University of Cambridge, UK

Dr Vincent Hanlon

University of Cambridge, UK

Vincent's work bridges the genetics of mutation and technology development for DNA sequencing. Previously, he worked on the accumulation of heritable somatic mutations in large old trees, before developing single-cell DNA sequencing protocols and associated bio-informatics for haplotyping and inversion-calling applications. Now his research focuses on the somatic diversification of HYP genes in Globodera plant-parasitic nematodes.

Strongyloides ratti is a common parasitic nematode of rats. It has c. 900 genes associated with parasitism. Among these are genes encoding astacin-like metalloproteases, acetylcholinesterases, CAP domain-containing proteins, and transthyretin-like proteins. Many of these genes are arranged adjacently in gene clusters referred to as "parasitism islands". In UK S. ratti populations these parasitism islands have higher levels of polymorphisms than other genomic regions. Most of these polymorphisms are non-synonymous, suggesting functional divergence among parasitism island gene products. To explore the functional impact of such variation in the island genes, we analysed genomes from twenty-five wild UK S. ratti genotypes using long-read sequencing and characterised their parasitism islands. We find that parasitism island structure is diverse among genotypes in terms of the number of islands, their genomic position, and gene composition. Focusing on astacin-like metalloproteases, structural protein modelling and alignment with experimentally-determine structures shows that over 85% of parasitism island encoded astacins lack the zinc-binding motif that is essential for protease activity. This loss contrasts with astacins encoded outside of parasitism islands, where most retain the motif and, presumably, protease activity. Because genes encoding these non-canonical, motif-deficient astacins are highly expressed, we suspect that they may have alternative, non-protease functions such as substrate binding, and phylogenetic analyses shows that their evolution is Strongyloides-specific.

Dr Mohammed Ahmed

University of Liverpool, UK

Dr Mohammed Ahmed

University of Liverpool, UK

Mohammed Ahmed is a nematologist and evolutionary biologist whose research spans the systematics, genomics, and evolutionary history of nematodes and other parasitic organisms. Trained in nematode taxonomy and phylogeny, he employs integrative morphological and molecular approaches to uncover hidden diversity and evolutionary relationships across the nematode phylum, particularly those from poorly known groups. His earlier work addressed the taxonomy and phylogenomics of terrestrial and marine nematodes, demonstrating expertise in bioinformatics and high-throughput sequencing. Currently, Mohammed is a postdoc at the University of Liverpool focussing on the parasitic nematode Strongyloides ratti, exploring the genomic basis of parasitism. His work highlights large-scale gene-expansion events linked to parasitic lifestyle evolution, strain-level genomic diversity within S ratti populations and evolution of parasitism gene families. This research aims to offer new insights into how S ratti evolved novel genetic toolkits to invade, exploit and persist within its hosts.

Caenorhabditis elegans primarily reproduces by self-fertilization, which leads to reduced levels of genetic diversity and potentially limits the adaptive potential of the species. In previous studies, we amassed 1,952 wild C. elegans strains collected from around the globe, sequenced the genomes using short-read technologies, and found that these strains contain punctuated genomic regions of extreme genetic diversity (hyper-divergent regions, HDRs) when compared to the reference N2 strain. These HDRs are enriched for genes associated with environmental responses such as xenobiotic stress and olfaction and might play a role in adaptation. However, the gene content of these regions remains incomplete because the extreme divergence in HDRs between the wild and reference genomes complicates short-read DNA alignments. To address this limitation, we generated de novo assemblies of 144 wild strains using PacBio HiFi long-read sequencing. We predicted protein-coding genes in these wild strain genomes, identified single-nucleotide and structural variants, and created a gene-based pangenome. Our gene-based pangenome has elucidated gene copy-number variation among wild strains, and we have identified hundreds of novel genes. We quantified levels of enrichment for structural variants, copy-number variants of specific genes, and novel gene birth in HDRs. This gene-based pangenome will be used to create new genotype matrices and perform genome-wide association mappings to connect gene content differences to phenotypic variation across the species, further elucidating the molecular mechanisms of adaptation and the role HDRs have in the long-term survival of this androdioecious species.

Mr Lance O'Connor

John Hopkins University, USA

Mr Lance O'Connor

John Hopkins University, USA

Lance is a third year Cell, Molecular, Developmental Biology, and Biophysics PhD Candidate at John Hopkins University. He earned his BS in Cellular and Organismal Physiology from the University of Minnesota in 2023 and enrolled at John Hopkins University to study computational genomics in Erik Andersen's laboratory. Lance received an honourable mention for his NSF GFRP application in 2025 and a Victor Corces Excellence in Teaching Award from John Hopkins University. He is interested in how intraspecies genetic variation shapes adaptive potential of species and how genotypic variation influences phenotypic variation.