Biology subjects

Robertson, E.

Publications and source records attributed to Robertson, E..

5 recordsLinked to original sources

bioRxiv2026

Loss of Adaptive Capacity Drives Climate Vulnerability Across Taxonomic Scales in an Alpine Specialist Species Complex

Accelerated warming at high elevations is having a disproportionate impact on alpine species. While assessments of climate vulnerability require quantifying the ecological and evolutionary components of adaptive capacity, such assessments are rare, especially in alpine systems. We leverage recent advances in population and landscape genomics to assess how variation in spatial heterogeneity and population connectivity across alpine systems influences adaptive capacity, using the North American Rosy-Finch species complex as a model system. In doing so, we clarify taxonomic relationships across the complex and identify one new ESU, the Sierra Nevada Rosy-Finch, based on its combined ecological and evolutionary distinctiveness. We then illustrate how combining genomic analyses with ecological data can improve estimates of adaptive capacity, sensitivity, and exposure and ultimately clarify climate vulnerability. Overall, our integrative analyses revealed that more isolated lineages, such as the Sierra Nevada Rosy-Finch, have lower adaptive capacity and face disproportionately high risks from climate change. This work highlights how conservation strategies that account for the multidimensional aspects of adaptive capacity can improve estimates of climate vulnerability.

evolutionary biology↗

bioRxiv2025

Single cell transcriptional evolution of myeloid leukaemia of Down syndrome

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), via a conserved sequence of mutations. Here, we examined the relationship between the genetic and transcriptional evolution of ML-DS from natural variation; a rich collection of primary patient samples and fetal tissues with a range of constitutional karyotypes. We distilled transcriptional consequences of each genetic step in ML-DS evolution, utilising single cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We found that transcriptional changes induced by the TAM-defining GATA1 mutations are retained in, and account for most of the ML-DS transcriptome. The GATA1 transcriptome pervaded all stages of ML-DS, including progressive disease that had undergone genetic evolution. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distilling consequences of mutations within their pathophysiological context.

cancer biology↗

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↗

bioRxiv2024

2-D organoids demonstrate specificity in the interactions of parasitic nematodes and their secreted products at the basal or apical intestinal epithelium

The intestinal epithelium is a selectively permeable barrier that absorbs water and nutrients, senses the luminal environment, and orchestrates submucosal immune responses. Some gastrointestinal nematodes occupy both submucosal and luminal niches and can cause profound changes in epithelial cells. Yet, there is little understanding of the specificity of parasite-host interactions with epithelial cells and the differential responses at the apical or basal sides. Organoids enable uncoupling of parasite-driven responses from immune-driven effects on the epithelium, and two-dimensional (2-D) organoids allow for controlled access to both sides. Here we used 2-D enteroids to model in vivo localisation of Heligmosomoides bakeri (H. bakeri) fourth-larval (L4) and adult stages and identify localisation-specific effects on gene expression. Using bulk RNA sequencing, we found an enhanced upregulation of IFN-stimulated genes (ISGs) during basal co-culture and an overall stronger response to L4 parasites than adults. Further, H. bakeri live worms induced much stronger effects on gene expression than their isolated excretory-secretory (ES), but cells that internalised H. bakeri extracellular vesicles (EVs) displayed up-regulation of ISGs, repair genes, and YAP/TAZ signalling. Our results demonstrate that nematodes and their products, including EVs, modify the host epithelium in a localisation-dependent and cell-specific manner.

immunology↗

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↗