Biology subjects

Hellgren, O.

Publications and source records attributed to Hellgren, O..

10 recordsLinked to original sources

bioRxiv2026

Parasite epigenetic memory and blood barriers dictate host transcriptional responses during generalist host-shifts

The evolutionary success of generalist parasites is often attributed to their capacity to rapidly navigate divergent host environments through transcriptional plasticity. While host-parasite dynamics are frequently studied in avian models, the immunogenic impact of the heterologous blood matrix, a critical variable in cross-species inoculation experiments, is rarely accounted for. In this study, we investigated the host-transcriptomic landscape of domestic canaries (Serinus canaria) infected with the avian malaria parasite Plasmodium homocircumflexum (lineage COLL4), employing a crosswise infection design to differentiate between homologous and heterologous donor sources. By implementing a factorial experimental framework, we successfully isolated the transcriptional noise induced by the heterologous blood matrix per se, revealing that mismatched transfusions trigger significant, non-specific innate immune activation independently of parasite presence. Upon correcting for this background effect, we observed distinct transcriptional trajectories: while adapted (homologous) infections induced a metabolic catalytic overload driven by key kinase hubs (e.g., AKT1, CDK6), heterologous infections were characterized by a shift toward structural and ribosomal regulation. These divergence patterns in the host, combined with the strain-specific transcription of the parasite, suggest that early infection phases are heavily constrained by recent host-switching events. Our results demonstrate that this epigenetic memory acts as a fundamental determinant of virulence, providing a new systems-based framework for understanding how pathogen history and host-donor compatibility reshape infection dynamics and host molecular outcomes during the colonization of novel ecological frontiers.

evolutionary biology↗

bioRxiv2026

The genome of the avian malaria parasite Haemoproteus majoris (lineage WW2) and its relationship to other Plasmodium species

Avian malaria parasites form a highly prevalent and genetically diverse group within the haemosporidians, yet they have long been overlooked relative to their human- and rodent-infecting counterparts. Among these, parasites of the genus Haemoproteus (Haemosporida, Haemoproteidae) are widespread and prevalent blood parasites of birds, transmitted by louse flies (Hippoboscidae) and biting midges (Ceratopogonidae). Recent phylogenomic analyses place Haemoproteus parasites at the root of the haemosporidian tree, making genomic data from these taxa essential for understanding the evolutionary origins of malaria parasites. To date, only two avian Plasmodium and one avian Haemoproteus genomes have been sequenced. We present the first assembled genome of Haemoproteus majoris (lineage WW2), a common blood parasite of passerine birds. As avian erythrocytes are nucleated, parasite DNA was enriched by FACS-based sorting to discriminate and isolate the parasite from host cell nuclei prior to whole-genome amplification. The genome was assembled using Nanopore long-read sequencing and polished with Illumina short-reads, yielding 145 contigs with a total assembly size of 23.9Mb and a G+C content of 27.85%. Genome annotation identified 5501 protein-coding genes, 69 non-coding RNA genes, and 57 long terminal repeat retrotransposons (LRT-RTs), including one full-length element. This genomic resource represents a critical step towards elucidating the evolutionary history and genomic architecture of avian malaria parasites. SIGNIFICANCE STATEMENTWe present the first assembled genome of Haemoproteus majoris (lineage WW2), a prevalent and generalist avian malaria parasite. Taxonomic resolution of this genus is difficult as there are few distinct morphological differences among closely-related species. This genome provides a valuable resource for studying the evolution within the Haemoproteus genus and to elucidate the evolutionary history of malaria parasites.

genomics↗

bioRxiv2026

Spatiotemporal and demographic effects on avian malaria prevalence in blue tits

While the ubiquity of parasites is well understood, the extent to which host demographic factors shape parasite prevalence patterns merits further investigation. Using 15 years of breeding data from blue tits (Cyanistes caeruleus) in southern Sweden, spanning a 26-year timeframe, we assessed the roles of host age, sex, and field site on the odds of infection with three avian malaria parasite genera: Haemoproteus, Plasmodium, and Leucocytozoon. Further, we also evaluated the effects of these demographics on the odds of triple-genus coinfections. We found first-year breeders have fewer infections with Haemoproteus and Plasmodium, and fewer triple infections compared to older age classes, suggesting that birds are accumulating infections over time. Leucocytozoon infections are more prevalent in males than in females, and this may be due to sex-specific differences in physiology. The prevalence of malaria parasites and their coinfections also vary between the three sampling sites, indicative of an effect of host breeding habitat, even at a relatively small spatial scale (neighboring sites were separated by <5km). Across all three field sites, prevalence is overall significantly increasing over time. For Haemoproteus, this increase is more pronounced in older birds compared to younger birds. Such temporal changes in age-related infection patterns would not have been apparent without long-term data thus highlighting the importance of long-term studies for informing our understanding of host demographic effects on parasite prevalence.

molecular biology↗

bioRxiv2025

Climate-driven increase in transmission of wildlife malaria parasite over the last quarter century

Climate warming is expected to influence the prevalence of vector-transmitted parasites. Understanding the extent to which this is ongoing, or has already occurred, requires empirical data from populations monitored over long periods of time, but these studies are sparse. Further, vector-disease research involving human health is often influenced by disease control efforts that supersede natural trends. By screening for malaria parasite infections in a wildlife population of blue tits (Cyanistes caeruleus) in Northern Europe, over a 26-year period, we tested whether observed prevalence and transmission changes were climate-driven and show that all three malaria parasite genera have increased significantly in their prevalence and transmission over time. The most common parasite in the study, Haemoproteus majoris, increased in prevalence from 47% (1996) to 92% (2021), and this is a direct consequence of warmer temperatures elevating transmission. Climate window analyses reveal that elevated temperatures between May 9th and June 24th, a time period that overlaps with the host nestling period, are strongly positively correlated with H. majoris transmission in one-year-old birds. Warmer climate during this narrow timeframe has a demonstrable impact on parasite transmission, and this permeates into the overall prevalence in the host population. We now have empirical support that climate warming can drive a rapid rise in vector-transmitted parasites, and this has implications for other host-parasite systems. Given that we now know the exact time of year when climate warming is most influential on a common vector-transmitted parasite in this system, it is possible to investigate the evolutionary and environmental mechanisms that underly how these infections ultimately manifest. While more challenging to measure, similar implications of climate warming on human vector-disease systems might be occurring.

ecology↗

bioRxiv2025

Generalist malaria parasites and host imprinting: Unveiling transcriptional memory

Generalist parasites must rapidly adapt to diverse host environments to ensure their survival and transmission. Parasites may employ fixed genetic responses, transcriptional plasticity, or epigenetic mechanisms to optimize survival. The avian malaria parasite Plasmodium homocircumflexum serves as an ideal model for studying transcriptional variation and adaptive strategies. We experimentally inoculated P. homocircumflexum into different bird hosts, bypassing vector recombination, to investigate whether parasite gene expression remains stable across hosts, resets in response to new environments, or reflects epigenetic inheritance. Our study evaluates four potential mechanisms: (1) A universal gene expression profile ("one key fits all"), where expression remains stable across hosts. Our outcomes revealed that gene expression differed significantly depending on the host species and time post-infection, thus rejecting this hypothesis. (2) Complete transcriptional plasticity, where gene expression is fully determined by the recipient host. Contrary to this hypothesis, we observed that gene expression was primarily influenced by the donor at 8 days post-infection (dpi), whereas gene expression was more aligned with the recipient host at 16 dpi. (3) Epigenetic inheritance, where early-stage gene expression reflects the donor host but gradually adjusts to the recipient. Our results support this mechanism, as 2,647 differentially expressed genes (DEGs) were associated with donors at 8 dpi, whereas 271 DEGs were linked to the recipient by 16 dpi. (4) Selection-driven differentiation favoring specific haplotypes. This latter hypothesis was not supported since SNP analyses showed low genetic differentiation. These findings suggest a P. homocircumflexum transition from donor-dependent to recipient-dependent gene expression, likely mediated by epigenetic regulation and transcriptional plasticity.

genomics↗

bioRxiv2024

Beyond immunity: a transcriptomic landscape of Plasmodium's modulation of mosquito metabolic pathways

The focus of mosquito-Plasmodium interactions has predominantly been centered on mosquito immunity, revealing key mechanisms by which mosquitoes attempt to combat Plasmodium infection. However, recent evidence suggests that beyond immunity, a multitude of mosquito physiological and metabolic pathways play crucial roles in determining whether the parasite completes its development within the mosquito. We review which of these metabolic pathways are potentially modulated by Plasmodium, revealing a fragmented and occasionally contradictory state of knowledge. We then present a comprehensive transcriptomic analysis of Plasmodium-infected and uninfected mosquitoes, examining gene expression of crucial genes across different stages of the parasites development. These genes range from key enzymes and proteins involved in gut structure and function, to genes involved in egg production and resorption, salivary gland invasion and mosquito behaviour. For this purpose, we use a non-model system consisting of the avian malaria parasite Plasmodium relictum, an invasive parasite threatening bird biodiversity across the world, and its natural vector, the mosquito Culex pipiens. Our results reveal how at each stage of its development within the mosquito, Plasmodium modulates a myriad of mosquito metabolic pathways, in ways that potentially favour its survival and the completion of its life cycle. We discuss whether this constitutes sufficient evidence of parasite-driven manipulation or whether the changes are simply the mosquitos response to the infection, which the parasite may serendipitously exploit to enhance its fitness. Our study extends the comparative transcriptomic analyses of malaria-infected mosquitoes beyond human and rodent parasites, and provides insights into the degree of conservation of metabolic pathways and into the selective pressures exerted by Plasmodium parasites on their vectors.

genomics↗

bioRxiv2022

Immune gene expression in the mosquito vector Culex quinquefasciatus during an avian malaria infection

Plasmodium relictum is the most widespread avian malaria parasite in the world. It is listed as one of the 100 most dangerous invasive species, having been responsible for the extinction of several endemic bird species, and the near-demise of several others. Here we present the first transcriptomic study examining the effect of P. relictum on the immune system of its vector (the mosquito Culex quinquefasciatus) at different times post-infection. We show that over 50% of immune genes identified as being part of the Toll pathway and 30-40% of the immune genes identified within the Imd pathway are overexpressed during the critical period spanning the parasites oocyst and sporozoite formation (8-12 days), revealing the crucial role played by both these pathways in this natural mosquito-Plasmodium combination. Comparison of infected mosquitoes with their uninfected counterparts also revealed some unexpected RNA expression patterns earlier and later in the infection: Significant differences in expression of several immune effectors were observed as early as 30 minutes after the ingestion of the infected blood meal. In addition, in the later stages of the infection (towards the end of the mosquito lifespan), we observed an unexpected increase in immune investment in uninfected, but not in infected, mosquitoes. In conclusion, our work extends the comparative transcriptomic analyses of malaria-infected mosquitoes beyond human and rodent parasites and provides insights into the degree of conservation of immune pathways and into the selective pressures exerted by Plasmodium parasites on their vectors.

evolutionary biology↗

bioRxiv2020

Gene regulation of the avian malaria parasite Plasmodium relictum, during the different stages within the mosquito vector

The malaria parasite Plasmodium relictum is one of the most widespread species of avian malaria. As is the case in its human counterparts, bird Plasmodium undergoes a complex life cycle infecting two hosts: the arthropod vector and the vertebrate host. In this study, we examine the transcriptome of P. relictum (SGS1) during crucial timepoints within its natural vector, Culex pipiens quinquefasciatus. Differential gene-expression analyses identified genes linked to the parasites life-stages at: i) a few minutes after the blood meal is ingested, ii) during peak oocyst production phase, iii) during peak sporozoite phase and iv) during the late-stages of the infection. A large amount of genes coding for functions linked to host-immune invasion and multifunctional genes was active throughout the infection cycle. One gene associated with a conserved Plasmodium membrane protein with unknown function was upregulated throughout the parasite development in the vector, suggesting an important role in the successful completion of the sporogonic cycle. Transcript annotation further revealed novel genes, which were significantly differentially expressed during the infection in the vector as well as upregulation of reticulocyte-binding proteins, which raises the possibility of the multifunctionality of these RBPs. We establish the existence of highly stage-specific pathways being overexpressed during the infection. This first study of gene-expression of a non-human Plasmodium species in its natural vector provides a comprehensive insight into the molecular mechanisms of the common avian malaria parasite P. relictum and provides essential information on the evolutionary diversity in gene regulation of the Plasmodiums vector stages.

evolutionary biology↗

bioRxiv2019

Early-life gut dysbiosis linked to mass mortality in ostriches

Dysbiosis in the vertebrate gut microbiome has been associated with several diseases. However, it is unclear whether particular gut regions or specific time periods during ontogeny are responsible for the development of dysbiosis, especially in non-model organisms. Here we examine the microbiome associated with dysbiosis in different parts of the gastrointestinal tract (ileum, caecum, colon) in a long-lived bird with high juvenile mortality, the ostrich. Individuals that died of gut disease (n=68) had substantially different microbial composition from age-matched controls (n=50) throughout the gut. Several taxa were associated with mortality (Enterobacteriaceae, Peptostreptococcaceae, Porphyromonadaceae, Clostridium) and some with survival (Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, Turicibacter). Repeated faecal sampling showed that pathobionts were already present shortly after hatching and proliferated in individuals with low diversity, resulting in mortality weeks later. The factors influencing seeding of the gut microbiota may therefore be key to understanding dysbiosis and host development.

microbiology↗

bioRxiv2018

The development of gut microbiota in ostriches and its association with growth

The development of gut microbiota during ontogeny in vertebrates is emerging as an important process influencing physiology, immune system, health, and adult fitness. However, we have little knowledge of how the gut microbiome is colonised and develops in non-model organisms, and to what extent microbial diversity and specific taxa influence changes in fitness-related traits. Here, we used 16S rRNA gene sequencing to describe the successional development of the faecal microbiota in juvenile ostriches (Struthio camelus; n = 71) over their first three months of life, during which time a five-fold difference in weight was observed. We found a gradual increase in microbial diversity with age, an overall convergence in community composition among individuals, multiple colonisation and extinction events, and major taxonomic shifts coinciding with the cessation of yolk absorption. In addition, we discovered significant but complex associations between juvenile growth and microbial diversity, and identified distinct bacterial groups that had positive (Bacteroidaceae) and negative (Enterobacteriaceae, Enterococcaceae, Lactobacillaceae) correlations with the growth of individuals at specific ages. These results have broad implications for our understanding of the development of gut microbiota and its association with juvenile growth.

microbiology↗