Teeth Tell the Story of the Genetic Code Behind Dental Evolution

Teeth are more than tools for chewing; they are a window into our evolutionary past. Dental features have long been studied in anthropology and biology because of their durability and variability, making them valuable for tracing evolutionary lineages and population histories. Recent research now reveals the genetic blueprint that shapes tooth morphology, offering insights into how specific genes influence dental size, shape, and developmental processes across human populations.

For decades, scientists have recognized that teeth vary greatly among individuals, populations, and species. Evolutionary adaptations — particularly dietary shifts — have driven changes in tooth size and morphology over millions of years. For example, the reduction in human tooth size over the last several millennia is often linked to softer diets made possible by food preparation techniques. However, within modern human populations, the extent to which genetics drives dental variation, as opposed to environmental factors, has remained unclear.

Researchers recently conducted a study on Colombians of mixed European, Native American, and African ancestry, analyzing three key dental dimensions: mesiodistal diameter (MDD), buccolingual diameter (BLD), and crown height. Their findings reveal that continental ancestry has a measurable effect on dental dimensions, with genetic variants inherited from Native American ancestors increasing tooth size. Among the 18 genome regions associated with dental morphology, the most significant findings centered on the EDAR gene.

The Role of EDAR in Tooth Morphology

The EDAR gene, previously associated with traits, such as hair thickness and shovel-shaped incisors, emerged as a major influencer of tooth size. Variants of EDAR found in Native American populations consistently increased tooth MDD along an anterior-to-posterior gradient, with more pronounced effects on incisors and canines than molars. This aligns with developmental studies showing that teeth form in a sequential anterior-to-posterior direction, making anterior teeth more sensitive to genetic changes.

The evolutionary impact of EDAR is further highlighted by its selective advantage in East Asian and Native American populations, where the gene’s V370A variant plays a role in multiple physical traits. In mice, disruptions in EDAR lead to significant enamel loss in incisors but milder effects on molars, mirroring the gradient seen in human populations.

PITX2 and HS3ST3A1 Impact Dental Development

While EDAR stole the spotlight, researchers also uncovered novel associations involving two critical genes: PITX2 and HS3ST3A1. Both genes are known for their roles in early dental development:

• PITX2 is a transcription factor essential for tooth morphogenesis. Mutations in PITX2 are linked to Rieger syndrome, a disorder characterized by dental abnormalities such as hypodontia. Mouse models lacking PITX2 exhibited changes in molar size and cusp shape, further underscoring its role in tooth development.
• HS3ST3A1 and its related gene HS3ST3B1 regulate sulfation processes crucial for dental development. Variants of HS3ST3A1 not only affect tooth morphology but also reveal an intriguing evolutionary twist: some alleles were inherited from Neanderthals. This Neanderthal introgression may have contributed to tooth size reduction observed in modern European populations.

Mouse Models Validate Genetic Findings

To confirm these associations, researchers turned to mouse models. Mice lacking PITX2 or HS3ST3A1/HS3ST3B1 displayed measurable changes in tooth size and shape. Notably, the first and third molars were particularly sensitive to these genetic disruptions, reflecting the sequential development of molars in both humans and mice. This sensitivity to gene expression changes supports the idea that early developmental processes are key to determining tooth morphology.

Implications for Evolutionary Biology and Dentistry

These findings provide crucial insights into the forces shaping dental evolution. While adaptations to diet drove long-term trends in tooth size reduction among hominins, modern variation in dental features may result largely from neutral genetic drift. However, the role of specific genes like EDAR, PITX2, and HS3ST3A1 highlights how evolutionary pressures can shape dental traits through both coding and regulatory genetic changes.

From a practical standpoint, understanding the genetic basis of dental morphology can inform clinical approaches to dental dysmorphologies. For example, identifying genes involved in tooth size and shape may lead to novel strategies for managing conditions like hypodontia or enamel defects.

Conclusion

This research marks a significant step forward in our understanding of dental genetics, combining evolutionary history with developmental biology. Teeth, it seems, continue to tell the story of our past, shaped by genetic blueprints inherited over millennia. By exploring the complex interplay of genes and evolution, scientists are unlocking new possibilities for understanding — and perhaps even reshaping — the future of dental health. Click here to read the study.