Differences in a specific region of the Neanderthal genetic code may have contributed to their distinctive protruding jawline, a study suggests. A Neanderthal and a human skull on display at the National Museum of Scotland (credit: Hannah long) The genetic changes identified have been linked to a gene involved in facial development in humans.The changes were found in a region of DNA within the so-called dark genome – the underexplored 98% of people’s DNA that doesn’t contain instructions for making proteins.The study, by researchers at the Institute of Genetics and Cancer (IGC), sheds light on how genetic variants in this area of the dark genome could influence modern human face shape. Genetic switches Once thought of as ‘junk’ DNA, experts now believe that the dark genome – or non-coding genome – has a crucial role to play in the body by controlling how, when and where genes are switched on or off.Scientists previously discovered that the expression of a gene called SOX9 – known to play a role in facial development in humans – is reduced in patients with Pierre Robin sequence (PRS), leading to an underdeveloped lower jaw.Patients with PRS have a section of DNA missing in the non-coding genome. This section of DNA, known as an enhancer, is responsible for switching on the SOX9 gene. When deleted, activity of the gene is altered, limiting jaw development.The study looked at whether tweaking of the same enhancer switch could lead to altered jaw shape across evolutionary time. Increased activity It used zebrafish models to explore how variations in DNA in the Neanderthal genome influence activity of the SOX9 enhancer switch. Researchers identified three variants in the same region of the dark genome in Neanderthals which increased activity of the enhancer during crucial stages of facial development, compared with the human version.This high level of enhancer activity was linked to a population of early developmental cells, called neural crest-derived progenitor cells, which play a crucial role in forming the skeletal structures of the face.The findings highlight the important role changes to enhancers may have played in the evolutionary divergence between humans and Neanderthals.The study, funded by the Medical Research Council, was published in the journal Development. We found the enhancer is active in an intriguing population of facial progenitor cells which contribute to jaw formation. Boosting its activity may have affected expression of the target gene SOX9 during development, perhaps contributing to some of the jaw shape differences seen between modern day humans and fossilised remains from Neanderthals. In the future, we are interested to explore other DNA sequence changes at this enhancer to understand their impact on human face shape variation and how they may contribute to disease Dr Hannah Long Study lead from the Institute of Genetics and Cancer Related links Read the study in Development The researchers behind the paper Hannah Long Research Group Tags 2025 Publication date 10 Nov, 2025
