Periodic Reporting for period 1 - MultiOmicsTox (Multi-view learning and quantitative genetics to identify the molecular basis of adaptation to chemical pollutants)
Reporting period: 2021-05-01 to 2023-04-30
The existing methods for setting regulatory limits on hazardous chemicals in the environment currently overlook the impact of population genetic variability on toxicity endpoints. These methods rely on arbitrary adjustments to account for this variability, which can lead to either over-regulation or under-regulation. To ensure accurate environmental risk assessment, it is best to consider the evolutionary potential and adaptive capacity of natural populations. MultiOmicsTox is a project that measures the genetic basis of chemical toxicity at the population level, considering natural selection. This understanding is essential for the development of evidence-based environmental protection policies and regulations pertaining to chemicals. The primary objective of the MultiOmicsTox project was to explore toxicity response pathways and investigate their roles in the adaptation process, using the model species Daphnia. By addressing the knowledge gap regarding the influence of genetic diversity on population-level responses to chemicals, this project has contributed valuable insights to the fields of evolutionary and toxicological genomics.
The MultiOmicsTox project focused on the utilization of multi-omics data obtained from a Daphnia population from Lake Ring, a well-characterized Danish lake in central Jutland. This lake has a historical record spanning 120 years, during which it underwent various pollution events such as eutrophication caused by sewage inflows, pesticide contamination from agricultural run-off, and subsequent recovery. The project specifically examined the response of Daphnia populations of genetically distinct genotypes, derived from identical clones to pesticide exposure.
The ecological history of the four Daphnia sub-populations in Lake Ring is well-documented. Through radiometric chronology and paleolimnological analysis of sediment, it was determined that the lake was relatively pristine until the late 1950s. Subsequently, human activities led to eutrophication and the introduction of pesticides, primarily carbamates, into the lake through agricultural run-off. From 1999 onwards, the lake has shown significant recovery from eutrophication and pesticide toxicity, indicating reduced land use in modern times. To capture the different ecological phases, genetically distinct lines of Daphnia sub-populations were established at the University of Birmingham, representing the pristine, eutrophication, pesticide, and recovery phases.
Genome analysis of the Lake Ring Daphnia revealed the impact of eutrophication and pesticides on the genetic diversity of the population, highlighting potential targets of natural selection in response to environmental changes. Transcriptomic analysis demonstrated context-dependent changes in pesticide response at both individual and sub-population levels. The project successfully identified potential novel candidate gene regulatory networks and potential toxicity pathways, shedding light on adaptive changes and their association with adverse outcome pathways.
While the model chemical insecticide used in this study was banned in European markets, the genes and gene regulatory networks uncovered hold promise as biomarkers for other pesticides with similar modes of action. These biomarkers have the potential to assess the impact of chemical exposure and monitor its effects on susceptible populations.
Continued sharing of the findings and insights from this research with various stakeholders can potentially contribute to regulatory decision-making processes. This includes supporting the development of targeted monitoring strategies and the implementation of appropriate mitigation measures to safeguard human health and the environment.
The ecological history of the four Daphnia sub-populations in Lake Ring is well-documented. Through radiometric chronology and paleolimnological analysis of sediment, it was determined that the lake was relatively pristine until the late 1950s. Subsequently, human activities led to eutrophication and the introduction of pesticides, primarily carbamates, into the lake through agricultural run-off. From 1999 onwards, the lake has shown significant recovery from eutrophication and pesticide toxicity, indicating reduced land use in modern times. To capture the different ecological phases, genetically distinct lines of Daphnia sub-populations were established at the University of Birmingham, representing the pristine, eutrophication, pesticide, and recovery phases.
Genome analysis of the Lake Ring Daphnia revealed the impact of eutrophication and pesticides on the genetic diversity of the population, highlighting potential targets of natural selection in response to environmental changes. Transcriptomic analysis demonstrated context-dependent changes in pesticide response at both individual and sub-population levels. The project successfully identified potential novel candidate gene regulatory networks and potential toxicity pathways, shedding light on adaptive changes and their association with adverse outcome pathways.
While the model chemical insecticide used in this study was banned in European markets, the genes and gene regulatory networks uncovered hold promise as biomarkers for other pesticides with similar modes of action. These biomarkers have the potential to assess the impact of chemical exposure and monitor its effects on susceptible populations.
Continued sharing of the findings and insights from this research with various stakeholders can potentially contribute to regulatory decision-making processes. This includes supporting the development of targeted monitoring strategies and the implementation of appropriate mitigation measures to safeguard human health and the environment.
The research project findings have revealed the importance of integrating genetic factors leading to the discovery of robust and reliable biomarkers. This integration significantly enhances the accuracy and dependability of toxicity assessments. Additionally, considering climate change scenarios is essential to anticipate and predict adverse outcome pathways in toxicity studies, ensuring their relevance and applicability in the future.