Applying evolutionary genetics to developmental toxicology and risk assessment

Area of Science:

• Evolutionary biology
• Toxicology
• Developmental biology
• Systems toxicology

Background:

• A communication gap exists between evolutionary biology and toxicology regarding developmental pathways and human birth defects.
• Current methods for identifying developmental toxicants need enhancement through interdisciplinary approaches.

Purpose of the Study:

• To apply evolutionary genetics to improve the design and interpretation of studies identifying human developmental toxicants.
• To bridge the gap between evolutionary biology and toxicology for better understanding of health and disease.

Main Methods:

• Reviewing molecular systems of stress response and cell-cell signaling pathways crucial for development.
• Revisiting teratology principles with advances in high-throughput screening, big data, and systems toxicology.
• Utilizing multiscale systems modeling, phylogenetic analysis, and comparative bioinformatics for cross-species extrapolation.

Main Results:

• Updated 18 consensual cell-cell signaling pathways and reviewed five molecular stress response systems.
• Highlighted the role of evolutionary history (phylogeny) in species-specific susceptibility (ontogeny).
• Demonstrated the value of evolutionary approaches in identifying molecular initiating events for adverse developmental outcomes.

Conclusions:

• Integrating evolutionary genetics with toxicology offers novel applications for developmental toxicity and risk assessment.
• An evolutionary developmental (evo-devo) perspective can advance the study of developmental origins of health and disease.
• This interdisciplinary approach enhances the identification and validation of developmental toxicants across species.