You know something I love about biology? The depth. The complexity that we don’t always
recognize at first. I remember when I first learned about Punnett squares-
I was in 9th grade - and there were practice problems with
eye color as the trait. But then, as we would explore more depth in biology,
we learned: eye color is actually very complex. It’s a polygenic trait with many genes and
that trait is so complex that it really doesn’t work like a simple Punnett square. In fact, even
traits that we often treat like a one gene trait – like attached or free earlobes - even that trait
isn’t quite that simple so we even mention that in our pedigree video when we use it as an example.
There are so many exceptions and details in biology, and
they are fascinating to discover. They are still there waiting for you to explore them,
even when you think you’ve mastered general biology. For a perfect example:
something I not too long ago learned in a graduate level biology course: the topic of epigenetics.
And I have to share it with you now. Just like I did when I called my sister at 11:02 pm on
a Wednesday night when I was covering it as part of my course: it’s that interesting. Epigenetics.
Consider identical twins. They have the same DNA code, right? But if one of them
develops a disease that has a major genetic component, it does not necessarily mean the
other one will also develop it. Even though the identical twins have the same genetic code. Why?
Recall your DNA has bases and those bases code for physical traits like your eye color, your hair
color, your height, and more. We learn about this in biology. But there’s something else at work
too. Epigenetic factors. I don’t mean to sound so dramatic with my voice when I say “epigenetic,:
but I really wish this had been something that I had learned about even when I was in high school.
Although, to be fair, scientists are still learning a lot about epigenetic factors and
this field is already more advanced than it was when I was when I was in high school.
The root “epi” can mean “above” which is fitting for the word epigenetic as “above genome.” You can
visualize this word as factors that work on the genome and change how the genome is expressed.
Let’s talk about epigenetic marks: these can influence gene activity.
One example is methylation. Methyl groups that are attached to DNA bases in certain locations
and they keep transcription from occurring. [some exceptions]
You remember transcription, right? It’s part of protein synthesis. You have the
DNA and you transcribe it to mRNA – that’s transcription. You have to do that because the
other part of protein synthesis is translation, and that’s when the mRNA is used as a template so
the correct amino acids will be brought in to eventually make a protein. But DNA methylation
can prevent transcription so the DNA that is methylated will not be actively transcribed.
Demethylation can remove methyl groups where those areas of DNA then could be actively transcribed.
Epigenetic marks don’t have to be on the DNA directly; they can also impact
the histones. Histones are proteins that DNA will be rolled up and wound around.
Often compared to a spool for the DNA. Histones, too, can have methyl groups attached which
would be histone methylation and this generally tends to prevent transcription. And we also want
to mention histone acetylation which is where acetyl groups are attached to certain parts of
the histones. NOW when acetyl groups are attached, this causes a change to how tightly histones grip
the DNA – the packing is more loose, and it allows transcription factors to access the DNA. There is
also histone deacetylation which removes acetyl groups and this will cause the DNA to be more
tightly wrapped around the histones. This intense packing will limit the access of transcription
factors and enzymes involved in transcription, and this can be used along with methylation.
Epigenetic marks liked the ones mentioned can impact which genes are expressed. And
that can make very big differences. Like what kind of difference? There are several examples
in rodents that we have referenced in our video details: one example is how parental care that
female rats have on their offspring – specifically whether female rats lick and groom their young
or not – can affect the control of the expression of the GR gene. The GR gene codes for receptors
that are involved in regulating the stress response in rats. Epigenetic marks, which in this
case are influenced by the mother rat’s behavior, can influence the transcription of the GR gene
in the offspring. Due to whether this GR gene is frequently expressed, or not, this can affect the
baby rats’ stress response and behavior even when they reach adulthood and have their own offspring.
Another example is the agouti trait in mice. Consider two mice that have the same DNA. Only
they don’t look alike because one of them is a brown mouse with an average mouse size
and the other is a yellow mouse with obesity. In the yellow mouse, a gene called the agouti gene is
being actively transcribed. The gene is not being actively transcribed in its twin; it is actually
methylated. And it turns out, the active agouti gene can affect more than the color as the agouti
mouse as it also makes this mouse prone to being obese and potentially prone to specific diseases.
Scientists found that the environment that a pregnant mouse is in – and the diet that
the pregnant mouse has- can impact whether the offspring will have this agouti gene active or
not, so it’s actually passed down. And, if a pregnant mouse is fed foods that are high
in methyl groups? Well, it turns out, this can decrease the expression of the agouti gene in
her offspring even if the pregnant mouse herself fully expresses the agouti gene.
Before I move on: two quick points I want to mention.
First point is about inheritance. So when an organism’s body cells divide in mitosis, the new
daughter cells can inherit the same epigenetic marks as the original cells they came from.
This can be inherited from cell to cell. Now, when a sperm cell and egg cell combine to form a
fertilized egg –which occurs in humans and many other organisms-
epigenetic marks are often “cleared.” Except some epigenetic marks are not cleared and can
therefore be inherited from parent to offspring in this way. See the further reading details.
#2, I don’t want to create a misconception that epigenetic marks are only something
influenced by the external environment. So, for example, you have so many different types
of specialized cells- after all, most of your human body cells contain your entire DNA code,
but generally your cells are actively transcribing certain genes based on the cell type. Meaning,
your eye cells and stomach cells aren’t actively transcribing the exact same genes.
Many of these genes are actively transcribed or not actively transcribed due to epigenetic
marks from internal cues in addition to external ones. It’s critical for human development too.
One last thing. You may wonder: why is the field of epigenetics
so important? Well, as we mentioned earlier, many diseases that have a genetic component
can involve epigenetics. Cancer can be an example, and cancer is one that personally
has affected our family and many other families. We talk about cancer in our cell cycle video.
And, yes, with cancer there is an uncontrolled growth of a person’s own cells,
and also as we mention in that video, those cells are not functioning like they should. And by not
functioning like they should, it can mean that there are genes that are actively transcribed
that should be turned off or genes that have been inactivated that should be actively transcribed.
In cancer cells, the epigenetic marks are often not arranged as they should be.
In a fascinating field known as epigenetic therapy, researchers are looking to advance
cancer treatment options and treatment for a lot of other medical conditions too
by targeting those epigenetic marks acting on the genome.
Overall, increasing our understanding of the epigenome – and by that, I mean the genome and
ALL of its epigenetic marks- will help all of us in better understanding how our cells
and bodies function. Well, that’s it for the Amoeba Sisters, and we remind you to stay curious.