Periodic Reporting for period 1 - EPI-TRADEOFF (Molecular trade-offs between adaptation to salinity and immunity in three-spined sticklebacks)
Reporting period: 2021-05-03 to 2023-05-02
To accommodate the stress induced by climate change, aquatic organisms face the choice of either moving to a better environment or adapting to changes. However, life history trade-offs limit the effectiveness of adaptation. Parasites and pathogens are widespread and exert strong selection pressure. Indirect changes in environmental salinity can impact immune defences and the survival of populations in their current environment. Adapting to salinity reduces the ability to respond to other challenges like parasites and diseases, which can disrupt immune functions and related genes.
Parasites play a role in evolution by promoting the fight against diseases in multiple manners, including tolerance. Tolerance enables hosts to endure infections without significant negative effects on their fitness and unlike resistance does not lead to the elimination of the parasites. Yet, the underlying mechanisms and possible heritability of this mechanisms remain unknown. In certain fish species, paternal infection is linked to increased disease tolerance in offspring, and infection is associated with DNA methylation. However, the precise role of DNA methylation in transmitting tolerance remains to be evidenced.
The primary objectives of our research were to:
1. Describe the methylation patterns related to immunity and salinity.
2. Identify genes involved in the trade-off of methylation between immunity and salinity.
3. Experimentally examine the induction of trade-offs through changes in salinity and parasite infection.
4. Functionally test the effects of methylation trade-offs on gene expression.
DNA methylation, an important epigenetic marks, plays a crucial role in understanding its transmission mechanisms and trade-offs among different stressors. This knowledge is essential in the fields of evolutionary biology and biodiversity conservation. Additionally, DNA methylation has been observed to change in relation to factors like age and cancer type, making our research relevant to various areas of biomedicine with potential significant implications.
We found a strong correlation between the infectious status of fathers and changes in the methylome of their offspring. This effect was so strong that the offspring infection status hardly predicted their methylation patterns compared to that of their father. Ultimately, we identified DNA methylation marks that were associated with tolerance, that could be used as potential biomarkers. Our results provide new insights into the molecular mechanisms underlying tolerance as well and trans-generational immune priming via the paternal line.
Parasites play a role in evolution by promoting the fight against diseases in multiple manners, including tolerance. Tolerance enables hosts to endure infections without significant negative effects on their fitness and unlike resistance does not lead to the elimination of the parasites. Yet, the underlying mechanisms and possible heritability of this mechanisms remain unknown. In certain fish species, paternal infection is linked to increased disease tolerance in offspring, and infection is associated with DNA methylation. However, the precise role of DNA methylation in transmitting tolerance remains to be evidenced.
The primary objectives of our research were to:
1. Describe the methylation patterns related to immunity and salinity.
2. Identify genes involved in the trade-off of methylation between immunity and salinity.
3. Experimentally examine the induction of trade-offs through changes in salinity and parasite infection.
4. Functionally test the effects of methylation trade-offs on gene expression.
DNA methylation, an important epigenetic marks, plays a crucial role in understanding its transmission mechanisms and trade-offs among different stressors. This knowledge is essential in the fields of evolutionary biology and biodiversity conservation. Additionally, DNA methylation has been observed to change in relation to factors like age and cancer type, making our research relevant to various areas of biomedicine with potential significant implications.
We found a strong correlation between the infectious status of fathers and changes in the methylome of their offspring. This effect was so strong that the offspring infection status hardly predicted their methylation patterns compared to that of their father. Ultimately, we identified DNA methylation marks that were associated with tolerance, that could be used as potential biomarkers. Our results provide new insights into the molecular mechanisms underlying tolerance as well and trans-generational immune priming via the paternal line.
In this project, we focused an elucidating the heritability of tolerance transmission seen in Kaufman et al. (2014), following the suggestion by Sagonas et al (2020) that methylation could be implicated. Specifically, we investigated the role of DNA methylation in the evolution of tolerance via the paternal line across generations of three-spined stickleback (Gasterosteus aculeatus). Using a new analytical framework applied to reduced representation bisulfite sequencing, we asked (1) whether offspring DNA methylation profile varies with paternal infection, and (2) whether DNA methylation correlates with tolerance in offspring. We found a strong correlation between the infectious status of fathers and changes in the methylome of their offspring. This effect was so strong that the offspring infection status hardly predicted their methylation patterns compared to that of their father. Ultimately, we identified DNA methylation marks that were associated with tolerance, that could be used as potential biomarkers. Our results provide new insights into the molecular mechanisms underlying tolerance as well and trans-generational immune priming via the paternal line. We are preparing two manuscripts that we expect to publish in high impact peer-reviewed journals.
The impact of parasite-mediated selection extends beyond the evolution of resistance. Disease tolerance is defined as the capacity to withstand infection without suffering its costs. The work achieved during the project fills a knowledge gap investigating the molecular basis of tolerance and its transmission across generations. We identified DNA methylation as candidate biomarkers of tolerance transmitted through the father’s line. Hitherto, this work provides the tools and conceptual framework to understand the evolution of tolerance and its genetic basis.
Our unprecedented perspective on intergenerational inheritance of disease tolerance is of high interest for the scientific community and will help to move the field of phenotypic plasticity in particular and of evolution in general forward.
The project integrates multidisciplinary approaches involving -omics technologies in the context of evolutionary biology and biodiversity conservation. This is in alignment with key policies including UN Sustainable Goals (2030)(goal 14 “life below water”), EU Biodiversity Strategy for 2030 and EU Green Deal. Many fish species are faced with parasitic infections (which already cost $1.9b annually). Similar, the trading of fish is associated with increasing infection. The project will have impacts in aquaculture, ornamental fish trading industry and as a guidance to governmental stakeholders.
Our unprecedented perspective on intergenerational inheritance of disease tolerance is of high interest for the scientific community and will help to move the field of phenotypic plasticity in particular and of evolution in general forward.
The project integrates multidisciplinary approaches involving -omics technologies in the context of evolutionary biology and biodiversity conservation. This is in alignment with key policies including UN Sustainable Goals (2030)(goal 14 “life below water”), EU Biodiversity Strategy for 2030 and EU Green Deal. Many fish species are faced with parasitic infections (which already cost $1.9b annually). Similar, the trading of fish is associated with increasing infection. The project will have impacts in aquaculture, ornamental fish trading industry and as a guidance to governmental stakeholders.