Citation:

Colbourne, J., J. Shaw, E. Sostare, C. Rivetti, R. Derelle, R. Barnett, B. Campos, C. Lalone, M. Viant, AND G. Hodges. Toxicity by descent: a comparative approach for chemical hazard assessment. Environmental Advances. Elsevier B.V., Amsterdam, Netherlands, 9:100287, (2022). https://doi.org/10.1016/j.envadv.2022.100287

Impact/Purpose:

Human health and ecotoxicology has typically been treated as separate fields in toxicology. However, it is increasingly becoming more known that the conservation of genes, pathways and their functions are widespread and that even non-vertebrate species share common genes and pathways with vertebrates (including non-mammalian species). This comparative phylogenetic approach evaluates homology across the animal kingdom to better understand what gene families are conserved between invertebrates and humans and other vertebrates, particularly focused on disease-relevant genes. It is anticipated that results from this study could pave the way to connect efforts and tools in the research arena of comparative toxicology, making better use of invertebrate species, where appropriate, for informing human and environmental health within the advancing non-animal testing global research agenda.

Description:

Toxicology is traditionally divided between human and eco-toxicology. In the shared pursuit of environmental health, this separation does not account for discoveries made in the comparative studies of animal genomes. Here, we provide evidence on the feasibility of understanding the health impact of chemicals on all animals, including ecological keystone species and humans, based on a significant number of conserved genes and their functional associations to health-related outcomes across much of animal diversity. We test four conditions to understand the value of comparative genomics data to inform mechanism-based human and environmental hazard assessment: (1) genes that are most fundamental for health evolved early during animal evolution; (2) the molecular functions of pathways are better conserved among distantly related species than the individual genes that are members of these pathways; (3) the most conserved pathways among animals are those that cause adverse health outcomes when disrupted; (4) gene sets that serve as molecular signatures of biological processes or disease-states are largely enriched by evolutionarily conserved genes across the animal phylogeny. The concept of homology is applied in a comparative analysis of gene families and pathways among invertebrate and vertebrate species compared with humans. Results show that over 70% of gene families associated with disease are shared among the greatest variety of animal species through evolution. Pathway conservation between invertebrates and humans is based on the degree of conservation within vertebrates and the number of interacting genes within the human network. Human gene sets that already serve as biomarkers are enriched by evolutionarily conserved genes across the animal phylogeny. By implementing a comparative method for chemical hazard assessment, human and eco-toxicology converge towards a more holistic and mechanistic understanding of toxicity disrupting biological processes that are important for health and shared among animals (including humans).

URLs/Downloads:

Record Details: