Environmentally induced DNA methylation – a passive biomarker or driver of genetic mutation?

About the Project

Project:

DNA methylation is a core epigenetic mechanism involved in regulating gene expression, mediating environmental responses, and potentially influencing genome evolution. However, the function of gene-body DNA methylation is debated. One hypothesis posits that gene-body methylation stabilizes gene expression by maintaining open chromatin structure. The other suggests that it acts as a mutagenic force, increasing cytosine deamination rates at CpG sites and thereby generating potentially heritable genetic changes. Determining whether gene-body methylation functions as a regulatory stabilizer or as a mutagenic driver is critical, as each implies a distinct role in risk assessment—either as a reversible biomarker of exposure or as a driver of transgenerational outcomes. Clarifying this distinction will shape how epigenetic data are used to monitor and predict population resilience in the face of environmental pollution.

Daphnia magna is a freshwater crustacean and OECD alternative to animal testing. It is uniquely suited to test these hypotheses in a risk assessment framework. It has dormant life stages which are preserved in lake sediments allowing resurrection of populations that share a common genetic origin but were exposed to distinct environmental pressure across decades. These temporal populations provide a rare resource to assess long-term methylation dynamics. The recent development of high-quality reference genome and epigenome for D. magna enables parallel measurement of methylation and genomic changes. Preliminary data from the Marshall lab has shown enrichment of DNA methylation at zero-fold and two-fold degenerate codon sites, supporting the idea that gene-body methylation may act as a functional mutagen. If confirmed at the population level, this pattern would indicate that DNA methylation contributes directly to heritable genetic change, an insight with major implications for environmental risk assessment.

Ob1 – Map temporal dynamics of gene-body methylation across environmental pressures.

Methylation patterns in Daphnia resurrected from multiple sediment layers with distinct pollution histories will be compared. This will reveal whether methylation reliably tracks environmental contamination levels, supporting its use as a diagnostic biomarker of historical and ongoing pollution.

Ob2 – Test the mutagenic potential of methylation and its genomic consequences.

By correlating methylation levels with genome divergence, we will evaluate whether gene-body methylation contributes to mutation rates. This addresses whether methylation signatures are transient signals of exposure or drivers of long-term genomic change across generations, a key consideration for regulatory frameworks.

Ob3 – Integrate gene function and expression to assess biomarker utility.

We will assess whether gene-body methylation patterns are linked to gene function, expression dynamics, and selection signatures. This will help define which methylation signals are stable and which are functional indicators for environmental risk assessment.

Training opportunities:

This project integrates ecotoxicology, experimental evolution, genetic sequencing via Nanopore and bioinformatic analysis, aligning with the Centre for Environmental Health and Sustainability. The Marshall lab works with CEHS and Professor Luisa Orsini (Centre for Environmental Research and Justice, University of Birmingham, proposed 2nd supervisor) to translate core mechanistic findings to human health related applications.

Enquiries

Project Enquiries to hjm32@leicester.ac.uk

To apply please refer to

https://le.ac.uk/study/research-degrees/research-subjects/genetics