Researchers have started to figure out how DNA fine-tunes faces. In experiments on mice, they have identified thousands of regions in the genome that act like dimmer switches for the many genes that code for facial features, such as the shape of the skull or size of the nose.
Specific mutations in genes are already known to cause conditions such as cleft lips or palates. Yet in the latest study, a team of researchers led by Axel Visel of the Lawrence Berkeley National Laboratory in Berkeley, California, wanted to find out how variations seen across the normal range of faces are controlled.
Though everybody’s face is unique, the actual differences are relatively subtle. What distinguishes us is the exact size and position of things like the nose, forehead or lips. Scientists know that our DNA contains instructions on how to build our faces, but until now they have not known exactly how it accomplishes this.
Visel’s team was particularly interested in the portion of the genome that does not encode for proteins — until recently nicknamed “junk” DNA — but which comprises around 98 percent of our genomes. In experiments using embryonic tissue from mice, where the structures that make up the face are in active development, Visel’s team identified more than 4,300 regions of the genome that regulate the behavior of the specific genes that code for facial features.
The results of the analysis were published on Thursday in the journal Science.
These “transcriptional enhancers” tweak the function of hundreds of genes involved in building a face. Some of them switch genes on or off in different parts of the face, others work together to create, for example, the different proportions of a skull, the length of the nose or how much bone there is around the eyes.
“If you think about face development, a gene that is important for both development of the nose and the mouth might have two different enhancers and one of them activates the gene in the nose and the other just in the mouth,” Visel said.
“Certainly, one evolutionary advantage that is associated with this is that you can now change the sequence of the nose or mouth enhancers and, independently, affect the activity of the gene in just one structure or the other. It may be a way that nature has evolved in which you can fine-tune the expression of genes in complex ways without having to mess with the gene itself. If you destroy the protein itself that usually has much more severe consequences,” he added.
In further experiments to test their findings, the scientists genetically engineered mice to lack three of the enhancers they had identified. They then used computed tomography scanning to build 3D images of the resulting mouse skulls at the age of eight weeks.
Compared with normal mice, the skulls of the modified mice had microscopic, but consistent, changes in the length and width of the faces, as expected. Importantly, all of the modified mice only showed subtle changes in their faces, and there were no serious harmful results such as cleft lips or palates.
Though the work was done in mice, Visel said that the lessons transfer across to humans very well.
“When you look at the anatomy and development of the mouse versus the human, we find that the faces are actually very similar. Both are mammals and they have, essentially, all the same major bones and structures in their skulls, they just have a somewhat different shape in the mouse. The same genes that are important for mouse face development are important in humans,” he said.
Visel said that the primary use of this information, beyond basic genetic knowledge, would be as part of a diagnostic tool, for clinicians who might be able to advise parents if they are likely to pass on particular mutations to their children.
Peter Hammond, a professor of computational biology at University College London’s Institute of Child Health, who researches genetic effects on facial development, said understanding how faces develop can be important for health.
“There are many genetic conditions where the face is a first clue to diagnosis, and even though the facial differences are not necessarily severe, the condition may involve significant intellectual impairment or adverse behavioral traits, as well as many other effects,” he said. “Diagnosis is important for parents as it reduces the stress of not knowing what is wrong, but also can be important for prognosis.”