title: Applying evolutionary genetics to developmental toxicology and risk assessment.
abstract: Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States. Electronic address: mckleung11@gmail.com.
authors.forename: Maxwell C K
authors.initials: MCK
authors.lastname: Leung
authors.affiliation: Institute for Advanced Analytics, North Carolina State University, Raleigh, NC, United States.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Procter
authors.affiliation: Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA, United States.
authors.forename: Jared V
authors.initials: JV
authors.lastname: Goldstone
authors.affiliation: Department of Invertebrate Zoology, American Museum of Natural History, New York, New York, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Foox
authors.affiliation: Department of Invertebrate Zoology, American Museum of Natural History, New York, New York, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: DeSalle
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Mattingly
authors.affiliation: Department of Invertebrate Zoology, American Museum of Natural History, New York, New York, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Siddall
authors.affiliation: Department of Environmental Health Sciences, University of Massachusetts, Amherst, MA, United States.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Timme-Laragy
mesh_terms: D000818:Animals; D019295:Computational Biology; D019143:Evolution, Molecular; D006801:Humans; D010802:Phylogeny; D018570:Risk Assessment; D049490:Systems Biology; D018600:Teratology
keywords: Birth defects; Developmental toxicology; Evo-Devo; Evolutionary genetics; High-throughput screening; Signaling pathways; Systems toxicology