Scientist Hannah Long and her team at the University of Edinburgh have discovered that specific regions of Neanderthal DNA are more effective at activating genes related to jaw formation compared to human DNA, which might explain why Neanderthals had larger lower jaws.
Neanderthal. Image credit: Natural History Museum Trustees.
“The Neanderthal genome shows a 99.7% similarity to the human genome, suggesting that the differences between the species contribute to variations in appearance,” explained Dr. Hanna.
“Both the human and Neanderthal genomes comprise around 3 billion characters that code for proteins and regulate gene usage in cells. Therefore, pinpointing regions that affect appearance is akin to finding a needle in a haystack.”
Dr. Long and her collaborators had a targeted hypothesis regarding where to initiate their search. They focused on a genomic area linked to the Pierre Robin sequence, a condition characterized by a notably small jaw.
“Some individuals with Pierre Robin sequence exhibit significant deletions or rearrangements in this genomic region that disrupt facial development and impede jaw formation,” stated Dr. Hanna.
“We speculated that minor variations in DNA could subtly influence facial shape.”
Through the comparison of human and Neanderthal genomes, researchers identified that in a segment approximately 3,000 letters long, there are just three one-letter differences between the two species.
This DNA segment lacks any specific genes but regulates the timing and manner in which genes, particularly SOX9, a crucial factor in facial development processes, are activated.
To demonstrate the significance of these Neanderthal-specific differences for facial development, researchers needed to confirm that the Neanderthal region could activate genes in the correct cells at the appropriate developmental stage.
They introduced both Neanderthal and human variants of this region into zebrafish DNA concurrently and programmed the cells to emit different colors of fluorescent protein based on whether the human or Neanderthal region was active.
By monitoring zebrafish embryo development, researchers observed that the cells crucial for lower jaw formation were active in both regions, with the Neanderthal regions showing greater activity than those of humans.
“We were thrilled when we first detected the activity in a specific group of cells within the developing zebrafish face, near the jaw, and even more so when we realized that Neanderthal-specific differences could modify this activity during development,” Dr. Long noted.
“This led us to ponder the potential implications of these differences and how we may explore them experimentally.”
Recognizing that Neanderthal sequences were more adept at activating genes, the authors inquired whether this would correlate with heightened activity in target cells, influencing the shape and function of the adult jaw as governed by SOX9.
To test this hypothesis, they administered additional samples to zebrafish embryos. They found that the cells involved in jaw formation occupied a larger area.
“In our lab, we aim to investigate the effects of additional DNA sequence differences using methods that replicate aspects of facial development,” Dr. Long said.
“We aspire to enhance our understanding of sequence alterations in individuals with facial disorders and assist with diagnostic efforts.”
“This research illustrates that by examining extinct species, we can gain insights into how our own DNA contributes to facial variation, development, and evolution.”
Findings are detailed in the journal Development here.
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Kirsty Utley et al. 2025: Variants derived from Neanderthals enhance SOX9 enhancer activity in craniofacial progenitor cells that shape jaw development. Development 152 (21): dev204779; doi: 10.1242/dev.204779
Source: www.sci.news
