Faces are sculpted by 'junk DNA'

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. But 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
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% 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 behaviour of
the specific genes that code for facial
The results of the analysis are
published on Thursday in 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," said Visel.
"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 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
In further experiments to test their
findings, the scientists genetically
engineered mice to lack three of the
enhancers they had identified. They
then used CT (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
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
behavioural 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
The technology to go beyond
diagnosis and make precise
corrections of the genome does not
yet exist and, even if it did, it is not
clear that changing genes or
enhancers to create "designer" faces
would be worthwhile. "I don't think it
would be desirable to even attempt
that. It's certainly not something that
motivates me to work on this," said
Visel. "And I don't think anyone
working in this field would seriously
view this as a possible motivation."