Toward Next-Generation Teratology: Understanding Developmental Vulnerability Through Evolutionary and Comparative Genomics.

Teratology, the study of congenital anomalies, has developed from a descriptive discipline into a mechanistic science focused on the proximate causes of developmental defects, meaning how such anomalies arise during development. However, a comprehensive understanding requires not only this mechanistic insight but also an evolutionary perspective on why developmental systems are susceptible to disruption, often following recurring yet diverse patterns. To better grasp this susceptibility, it is important to consider evolutionary contexts, including concepts such as evolutionary trade-offs, environmental mismatch, and the intrinsic properties of developmental constraints. This perspective is now greatly enriched by advances in genome sequencing technologies. In this review, we revisit the concept of teratology within an evolutionary framework, and highlight the profound impacts of modern genome sequencing technologies, which are reshaping our view of teratology, evolutionary biology, and life science as a whole. We proceed to explore developments in three key research areas, each corresponding to a different evolutionary timescale: vertebrate appendage patterning and its evolutionary origins, whole-genome duplication and ohnolog evolution as sources of developmental complexity and dosage sensitivity, and deeply conserved chromosomal organization and transposable-element dynamics across animal evolution. Finally, we propose a future direction for "next-generation teratology" that fully integrates evolutionary and comparative genomics with conventional teratology to provide novel approaches to understand, diagnose, and ultimately prevent congenital anomalies.