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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - TGIP (Trans-generational immune priming: molecular basis and fitness consequences)

Teaser

Summary

In the face of rapid ongoing environmental changes currently experienced by species, the survival of species is challenged. The belief that species potential to adapt to a changing environment relies solely on their genetic diversity and demography is been questioned by phenotypic plasticity. More recently, the discovery of environment-sensitive molecular processes that accelerate phenotypic variation opened new research avenues. Although the view that these non-genetic components may control species adaptive capacity is vigorously debated, if even partly true, could have profound implications for understanding species adaptive potential.
Epigenetic components constitute important environment-sensitive mechanisms possibly accelerating responses to selective pressures. Even though there are several epigenetic pathways that can facilitate phenotypic plasticity, the addition of a methyl group to cytosine nucleotides in genesâ€™ promoters is probably the best characterized to date.
An emerging threat from globalization to species is the uncontrolled spread of parasites and diseases. Parasites alter a hostâ€™s fitness, influence populations, communities and ultimately ecosystem functions. Therefore, understanding the mechanisms of hostâ€™s resistance to pathogens is crucial. Importantly, at birth, where individuals mostly experience the same pathogenic environment as that of their parents, developing a rapid system for the transmission of labile resistance would appear beneficial.
Thus far, the idea that mothers can alter offspring immune response and resistance via the transfer of immune cells either through the egg yolk or the placenta is widely accepted. Recently, scientists proposed that males may also contribute to offspring parasite resistance beyond the simple transfer of genetic material, also referred as paternal effects. But to what extend these effects alter the outcome of ecological interactions, such as hosts\' parasite resistance is far from clear. Furthermore, their underlying mechanism remains poorly understood.
By conducting a control infection experiment, we showed that paternal effects on parasite resistance exist. Most importantly, we provide evidence that the underlying mechanism of the trans-generational immune priming is DNA-methylation and modifications that are induced by the parasites can be transmitted across generations. This provides a fast way for offspring to effectively react to pathogens experienced from their parents.

Work performed

Investigating the contribution of parental effects on host-parasite resistance and understanding the underlying mechanisms of this effect was the overarching goal of this proposal. To tackle our questions, we combined quantitative breeding in the laboratory and state of the art next-generation genomic approaches.
To fully take advantage of all opportunities inherent from NGS approach, during the first four months of the Fellowship I received training in bioinformatics and expand my knowledge into the field of host-parasite interactions and genome evolution. Furthermore, I attended the Home Office Licensee Training Course where I studied the National Legislation and Ethics of laboratory animals to gain a Personal License.
Perhaps the major risk of this project was associated to the identification of genomic regions responsible for parasites resistance and prone to epigenetic changes. Î‘n already pubic stickleback genome exists for guiding the screen of those genomic region. However, this reference was generated from an American population with long divergence time. This might prevent us from identifying recently evolved genomic regions and key ecological functional genes involved under selection in response to environmental factors, such as parasites that studied herein. Therefore, in the first phase of the project we generated a high-quality local reference genome. To produce this genome, we used PacBio long reads and Illumina short reads sequencing technologies and conducted a hybrid de novo assemble approach.
To test if parental infection leads to epigenetic modifications on hosts cell methylome linked to parasite resistance and if these modifications are transferred across generations, we conducted a controlled laboratory infection experiment, using the three-spined stickleback (Gasterosteus aculeatus) and one of its natural trophically transmitted nematode parasite (Camallanus lacustris). Thus far, the mechanisms to transfer immune response and parasite resistance, were assumed to functionally be restricted to mothers, whereas paternal effect has been neglected. To this end, here we focused on paternal transgenerational immune priming. For all fish we quantified body condition, immune response, parasite resistance and fertilisation ability. Our findings on paternal effects revealed that non-genetic resistance to parasites exists and infected offspring from infected fathers had higher body condition, fitness, fertilization ability and immune response than infected offspring from uninfected fathers.
Yet, what is the underlying mechanism of this increase resistance to parasites awaited investigation. To do so, in the second year we screened the DNA methylation profile of G1 and G2 fish . Our results revealed that exposure to parasites modify the DNA methylation pattern and induce changes in genomic regions related to immune response and fitness traits. Most importantly, we found that a number of epigenetic modifications associated to parasite resistance can be transferred from infected fathers to their offspring. In other words, infected offspring of infected fathers shared more methylated sites (15.5%) than infected offspring of uninfected fathers (6.3%).
Thus far this project has generated outputs that could be of interest to a wide range of scientific research fields. To disseminate the results of the inheritance of paternal effects on parasite resistance I participated at the conference of the European Society of Evolutionary Biology in Groningen, Netherlands (August 2017) and gave lecture at Queen Mary University of London (UK) and GEOMAR in Kiel (Germany). Furthermore, at the upcoming conference of Evolution in Montpellier, France I will present the findings of the changes induced by parasites on hostsâ€™ DNA methylation and their association to parasite resistance. On top of that two manuscripts are in preparation to be submitted in high impact factor journals, while the produced data will be annotated and made pub

Final results

Our early findings provide evidence of the role of DNA methylation as a suitable marker of parasite resistance and hosts physiology. Yet, to fully understand their relative contribution of mendelian versus non-Mendelian inheritance to parasite resistance we need to conclude all of the major objectives of this grant. Upon a successful completion of the project, results will have a great impact in the scientific community and wide implications for diverse research areas since they i) could revolutionize management of wildlife diseases by developing bioindicators to monitor genes associated to fitness and parasite resistance and ii) improve supportive breeding programs of endangered species and stocking. By illustrating the relevance of epigenetics on heritable phenotypic variants we could also propose to extend the evolutionary significant units to incorporate epigenetic variation.