Research led by scientist Hannah Long at the University of Edinburgh has found that specific regions of Neanderthal DNA are more effective at activating genes responsible for jaw development than those in humans, potentially explaining why Neanderthals had larger lower jaws.
Neanderthal. Image credit: Natural History Museum Trustees.
“With the Neanderthal genome being 99.7% identical to that of modern humans, the variations between species are likely to account for differences in appearance,” Dr. Hanna stated.
“Both human and Neanderthal genomes consist of roughly 3 billion characters that code for proteins and regulate gene expression in cells. Identifying the regions that influence appearance is akin to searching for a needle in a haystack.”
Dr. Long and her team had a targeted approach, focusing on a genomic area linked to the Pierre Robin sequence, a condition marked by an unusually small mandible.
“Individuals with the Pierre Robin sequence often have significant deletions or rearrangements in this portion of the genome that affect facial development and restrict jaw formation,” Dr. Hanna explained.
“We hypothesized that minor differences in DNA could produce more nuanced effects on facial structure.”
Upon comparing human and Neanderthal genomes, researchers discovered that in this segment, approximately 3,000 letters long, there are only three one-letter variations between the species.
This DNA region doesn’t code for genes but regulates when and how certain genes, particularly SOX9, which plays a crucial role in facial development, are activated.
To confirm that these Neanderthal-specific differences were significant for facial development, scientists needed to demonstrate that the Neanderthal version could activate genes in the appropriate cells at the right developmental stage.
They introduced both Neanderthal and human versions of this region into zebrafish DNA and programmed the cells to emit different colors of fluorescent protein based on the activation of either region.
By monitoring zebrafish embryo development, researchers observed that cells responsible for forming the lower jaw were active in both human and Neanderthal regions, with the Neanderthal regions showing greater activity.
“It was thrilling when we first noticed the activity of specific cell populations in the developing zebrafish face, particularly near the forming jaw, and even more exhilarating to see how Neanderthal-specific variations could influence activity during development,” said Dr. Long.
“This led us to contemplate the implications of these differences and explore them through experimental means.”
Recognizing that Neanderthal sequences were more effective at activating genes, the authors questioned whether this would lead to enhanced target activity affecting the shape and function of the adult jaw, mediated by SOX9.
To validate this idea, they augmented zebrafish embryos with additional samples of SOX9 and discovered that cells involved in jaw formation occupied a larger area.
“Our lab aims to further investigate the effects of genetic differences using methods that simulate various aspects of facial development,” Dr. Long remarked.
“We aspire to deepen our understanding of genetic variations in individuals with facial disorders and improve diagnostic processes.”
“This study demonstrates how examining extinct species can enhance our knowledge of how our own DNA contributes to facial diversity, development, and evolution.”
The findings are published in the journal Development.
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Kirsty Utley et al. 2025: Neanderthal-derived variants enhance SOX9 enhancer activity in craniofacial progenitor cells, influencing jaw development. Development 152 (21): dev204779; doi: 10.1242/dev.204779
Source: www.sci.news
