Have you ever wondered why you are the way you are? Are you "you" because of your
genes? Because of how you were raised or could it be both?
Welcome back to BOGObiology
and for this screencast we're going to discuss the concept of
epigenetics and how it helps us to understand the interactions of nature
and nurture in development. Traditionally, we've said that acquired traits are not
inherited, and this is true most of the time. For instance, this creature has
yellow fur. It can choose to dye its fur neon pink, but it's still going to
produce yellow offspring. However, as we learn more about genetics, we've come to
realize that experiences actually can change gene expression. Factors such as
diet, drug use, and chemical exposure can have a profound impact on our bodies.
All three of these factors are capable of changing which genes are active and
which genes are inactive. We used to believe that these changes in gene
activation could not be passed on to offspring. However, we're recently
discovering that these changes actually are heritable and can be passed on to
children, grandchildren, and sometimes even great-grandchildren. Their genetic
code itself has not been modified, but we have slightly changed which sections are
active and which sections are inactive. These are heritable changes in gene
expression that do not arise from changes to the DNA sequence itself. This
is what we call epigenetics. Another way to think about this is that we've
changed the organism's phenotype without changing its genotype. Understanding gene
expression is crucial to understanding epigenetics, so here's a quick review.
To begin with, every cell in the body contains the exact same DNA code.
DNA acts like a blueprint for making every kind of protein that the body needs.
The DNA is coiled up tightly inside the nucleus of the cell. A gene is a section
of DNA that codes for a particular set of characteristics. Each cell type
requires different traits, and thus they need to make different proteins.
The cell uses one DNA code to make many proteins by utilizing different sections for
different purposes. One cell type might use a certain section of the DNA
molecule, and another type might use a different section. If the gene is in use
and coding for proteins, we say that it is either "turned on" or "expressed".
So, how exactly does epigenetic influence gene expression? There are
actually a number of mechanisms, but the two about which we know the most are DNA
methylation and histone modification. Remember that the interior of the DNA
molecule is made up of four nitrogen bases; adenine, thymine, guanine, and
cytosine, and that these are connected together by hydrogen bonds.
Methyl groups, which look like this, can attach to the DNA molecule. These methyl groups can
attach to some of the cytosine nitrogen bases. The methyl groups prevent RNA
polymerase, a key enzyme in the manufacturing of proteins, from
effectively grabbing onto the DNA molecule. Since this section of DNA can
no longer be used to code for proteins, we now call it a "silenced" gene. The gene
has effectively been turned off. DNA is normally wrapped very tightly
around protein complexes known as histones. It unspools a little bit at a
time in order to be accessed and used, kind of like an old-fashioned
reel-to-reel film. Adding methyl or acetyl groups to histones impacts the
ease with which they unspool. As with DNA, methylation, the addition of a methyl
group, will inhibit the manufacturing of proteins from a certain gene. This is
because the methyl group attaches to the histone and causes the DNA to coil more
tightly, making it more challenging for enzymes to gain access. Adding an acetyl
group has the opposite effect. Acetyl groups are thought to loosen the wrapped
DNA, making certain genes more accessible. The process of both methylation and
acetylation of histones is actually reversible; the addition and removal of
these groups is done by enzymes and can be repeated many times.
Research has shown that exposure to toxic chemicals or a lousy diet can cause these acetyl
and methyl groups to bind in the wrong place, and either activate or silence the
wrong genes. This is especially problematic if, for instance, the error
caused a tumor suppressor gene to be silenced. Now let's talk about a few
examples. We'll begin by discussing Agouti Mice. Certain mice have a mutation
in a gene called the agouti gene. The mutation makes them obese and yellow, as
well as being susceptible to heart disease and diabetes. We would expect
these unhealthy mice to give birth to unhealthy offspring, but in 2003,
Waterland and Jintle showed that it was possible to silence the agouti
mutation. The female mice were fed a diet that was rich in methyl groups.
The methyl groups seemed to silence the agouti gene, and the offspring were born
healthy. Studies have also shown correlations between human maternal
health and the health of the offspring. We encourage mothers to eat folic acid
before and during their pregnancy because it helps with proper neural tube formation.
Another famous experiment showed the effect of epigenetics on the
stress response. inside of the midbrain of a rat is a region known as the
hippocampus. Within the hippocampus are structures known as glucocorticoid
receptors, which help mediate the stress response. Receiving adequate care early
in life seems to be a key factor. Baby rats who receive adequate care and
grooming from their mothers in the first weeks of life appeared to demethylate
the genes for glucocorticoid receptor development. When we remove the methyl
groups, it switches the genes on and allows for proper development of
glucocorticoid receptors within the hippocampus. These rats generally grow up
to become healthy and well-adjusted adults. If baby rats do not receive
adequate care, however, they never developed the same level of glucocorticoid
receptors. They also grew up to be highly anxious adults who had a very difficult
time managing their stress response. There appears to be a strong
relationship between maternal care and the development of a healthy stress
response later in life. Researchers are looking into the possibility of a
similar relationship in humans by studying victims of childhood trauma.
Hopefully, in years to come, we will continue to expand our knowledge of
epigenetics, how it impacts our lives, and the extent to which epigenetic changes
might be reversible.
All right, that's pretty much it for this week. If you
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