Study Uses Neanderthal DNA to Gain Insights into Modern Human Facial Development

Human faces are unique, yet the genetic factors shaping our facial features remain largely unclear. Scientists from the University of Edinburgh are investigating how differences in DNA between modern humans and our ancient relatives, the Neanderthals, influence facial development. Neanderthals had distinct features including large noses, pronounced brow ridges, and robust lower jaws. Researchers focused on a region of Neanderthal DNA linked to face and jaw formation, finding it activates a gene called SOX9 more strongly than the comparable human DNA sequence. 

The Neanderthal genome shares 99.7% similarity with modern humans, making the small genetic differences significant in altering physical appearance. By comparing this specific DNA region, about 3,000 letters long, researchers identified only three distinct genetic variations between Neanderthals and humans. This region does not contain genes itself but regulates the timing and degree to which SOX9 is activated. To test the functional impact, scientists inserted both Neanderthal and human versions of this region into zebrafish DNA, tracking gene activity through colored markers during development. They observed that the Neanderthal DNA region was more active in cells contributing to the jaw, which is consistent with Neanderthals' larger lower jaws.

“It was very exciting when we first observed activity in the developing zebrafish face in a specific cell population close to the developing jaw, and even more so when we observed that the Neanderthal-specific differences could change its activity in development,” said Hannah Long, senior author of the study published in Development. “This led us to think about what the consequences of these differences could be, and how to explore these experimentally.” Knowing that the Neanderthal sequence was more powerful at activating genes, Long and colleagues then asked if the resulting increased activity of its target, SOX9, might change the shape and function of the adult jaw. To test this theory, they provided the zebrafish embryos with extra SOX9 and found that cells that contribute to forming the jaw occupied a larger area.

“In our lab, we are interested in exploring the impact of additional DNA sequence differences, using a technique that mimics aspects of facial development in a dish. We hope this will inform our understanding of sequence changes in people with facial conditions and inform diagnosis,” added Long.