From X-Men to Ninja Turtles to the meta-humans of Static Shock,
science fiction is full of mutants, complete with laser eyes, weather control, and telekinesis.
And in these media, mutations seem to be the thing separating the humans — or, uh, turtles — from
the superhumans — or superturtles. But the truth is, everyone has mutations.
These complex genetic changes can be helpful, harmful, or just neutral.
And while mutations haven’t led to bonafide superheroes yet, there are mutations that have
given us some pretty unique abilities. Like the ones that let some of us
experience the wonders of coffee by metabolizing caffeine more efficiently.
Or the mutations that let some people feel rested with less sleep than others.
But there are also mutations that can cause conditions that shorten people’s life
expectancy and affect critical bodily functions. So the more we learn about how mutations really
happen — outside the movies — the more we can help people live healthier lives.
Hi! I’m Dr. Sammy, your friendly neighborhood entomologist, and this is Crash Course Biology.
I think I left the theme music in my super suit.
Has anyone seen my super suit? Where is my super suit??
The word mutation comes with a lot of baggage from popular culture.
But a mutation is simply a change in an organism’s genetic code, alternatively called a variation.
You see, DNA contains sequences of nucleotide bases,
and each base is represented by a particular letter: A, T, G, or C.
Stretches of these sequences of letters make up genes.
And genes are like recipes for countless types of proteins that organisms rely on.
A mutation occurs when the letters in DNA are altered.
This can sometimes change the protein that that section of DNA codes for, the way a new
ingredient can totally change a dish — like if you accidentally added sugar instead of salt.
Which, trust me, will really ruin your date night.
But mutations can also happen in DNA that doesn’t code for proteins.
These mutations occur quite often with no real effect — kind of like the garnish on your plate.
And mutations can happen for a variety of reasons. For example, there might be an error during DNA
replication, a process that’s happening pretty much constantly in the cells of your body.
Or, an organism might be exposed to a mutagen, a chemical or physical factor that can kickstart
changes in DNA, like UV radiation from the sun or the chemicals in tobacco products.
Sidenote: mutagens in fiction create smart-mouthed karate turtles named after Renaissance artists.
Mutagens in real life often produce non-functional cells or even cancers.
And yeah, that includes nuclear radiation, though as far as we know, there are
probably no radiation-induced Godzilla-sized lizards lurking beneath the Pacific Ocean.
The Marianas Trench is pretty deep though…so the chances aren’t actually zero.
Anyway, there are also some mutations that are considered inherited mutations because they can
be passed down from parent to offspring. This includes hemophilia, for example — a
condition that makes it harder for your blood to clot properly.
Now, like life itself, mutations are diverse, and their effects vary wildly.
But there are two main factors that help to determine the effects of a mutation.
The first is location.
Different cells, in different parts of the body, can end up with the same mutation.
But the effects are going to look different in cells that
create your heart muscles versus cells coding for proteins in your brain.
So, where a mutation occurs in the body is going to help determine its impact.
A mutation that occurs after conception is called a somatic mutation, and it can occur anywhere
in the body except the egg or sperm cells. Somatic mutations don’t get passed on genetically.
But, if an organism develops a mutation in one of its egg or sperm cells, well, that altered DNA
could be passed to all of its offspring’s cells. This is called a de novo mutation.
The second big thing that helps determine a mutation’s outcome is the “how” factor.
How did the mutation alter the DNA?
One common “how” is substitution, where one nucleotide is substituted for a different one.
Depending on which letter is swapped, this could mean nothing noticeable happens,
or it could potentially affect the entire organism.
For instance, the nucleotides G-A-A tell a cell to add glutamic acid to the protein it’s building.
If that code changes by a single letter to become G-U-A,
the cell will instead add valine, a completely different amino acid.
This type of substitution is called a missense mutation,
and it creates a different protein that might not work as intended.
This one-letter mutation causes sickle cell anemia, a disease affecting red blood cells.
Think of it this way, your DNA is an instruction manual
that has to be followed to the letter, literally.
So changing even one letter can alter the instructions.
Imagine if the instructions said “make a hatchet” but because of a mutation the “h”
in “hatchet” became an “r”. Instead you’d get a ratchet
and no matter how hard you try, a ratchet can’t split logs as handily as a hatchet.
Alternatively, G-A-A could become U-A-A, a stop codon.
This code tells a cell that whatever protein it’s building is finished – even when it’s not.
And this can stop production, resulting in a fragment rather than a complete protein.
This type of mutation is called a nonsense mutation, and it’s been linked to some serious
diseases, including cystic fibrosis — a genetic condition that affects the lungs and other organs.
There are also silent mutations, which might be a misleading name.
See, for decades, scientists thought a lot of substitutions didn’t do anything,
because genetic codes have a certain amount of redundancy.
For example, G-A-A codes for glutamic acid, but so does G-A-G.
So, if this last letter mutated from an A to G,
nothing would happen, or at least that’s what we thought.
Until, in 2022, a study on yeast found that these mutations still hurt the yeast’s ability
to reproduce in more than 75 percent of cases. Even if silent mutations weren’t changing the
molecules in a protein, they were affecting when and how often proteins were made.
More research needs to be done to see how this applies to other organisms,
but there’s a chance that these silent mutations aren’t so silent after all.
Another way mutations can happen is if nucleotides get deleted,
or extra ones get inserted. These are called frameshift
mutations: when this happens, the entire protein-building process is thrown off.
To understand why, let's play a quick imagined game called Threeopoly.
Where the only rule is this: after every three letters, you /have/ to
add a space – whether the word makes sense or not. So, round one, translate this string of letters ….
I’ll wait.
All right, times up! If you said:
“The big old cat sat.” you are correct! Ten points to all you old cat lovers.
Ready for round two? This time we have one
extra letter. And…go!
I’ll keep waiting.
That’s time…so the new correct answer is… “Tho
ebi gol dca tsa t.” That makes no sense.
This is what happens in a frameshift mutation. Since the letters in DNA are read in groups
of three, if you add even one extra letter, or take one away, that rhythm is disrupted,
and you could end up with a completely different protein.
Now, it’s important to remember that mutations aren’t harmful by default.
They’re just changes to the genetic code,
and their outcomes fall on a spectrum from positive, like the one that helps you feel
rested without a full eight hours of sleep, to negative, like cancer.
For instance, if you’re an adult who can chug a huge glass of milk without getting a stomach ache,
you probably have mutations to thank for your lactose tolerance!
Other mutations can protect people against HIV,
prevent severe cases of malaria, and reduce the risk of heart attacks.
And of course, mutations can be neutral, too. They might cause a change that doesn’t affect
an organism’s ability to survive — or even a change so small that it’s imperceptible.
While we can take some preventative measures to avoid certain types of harmful mutations,
like applying sunscreen to minimize exposure to UV radiation.
Ultimately, mutations are inevitable because our bodies aren’t perfect machines – we age.
Aging means both an accumulation of mutations
themselves, but also DNA damage from exposure to, well, living.
And while there really isn’t any science to back up a reversal of the aging process, recently,
scientists have developed techniques to create and reverse mutations manually.
They’re able to take control of something that used to be largely uncontrollable.
And although these methods are still in development,
this sort of gene editing could mean big things for medicine in the future.
I’m talking about gene therapy. Scientists can use a modified virus,
for example, to introduce a healthy copy of a gene into someone’s body.
The virus won’t get them sick, but it will give
their cells new instructions for how to make functional proteins.
Scientists can even use gene therapy to turn off genes with problematic mutations.
Gene therapy has had limited success so far, but it could eventually be used to treat everything
from AIDS to heart disease to cancer. And it’s not even the most
powerful tool scientists have. That honor, arguably, goes to CRISPR, genetic
scissors capable of some pretty cool things. Let’s check them out in the Thought Bubble…
This bacterium might look like Mardi Gras beads, but don’t be fooled:
Streptococcus pyogenes can really rain on your parade.
It causes strep throat, scarlet fever, and more. But by studying this microbe, scientists
unexpectedly discovered a pretty impressive gene-editing process.
You see, this strep throat-causing bacterium has its own ancient immune system.
So even as the bacterium makes you sick, there are harmful viruses that would make it sick.
To disarm them, it uses that immune system, called CRISPR/Cas, to chop up viral DNA.
And in 2020, scientists Emmanuelle Charpentier and
Jennifer Doudna won the Nobel Prize in Chemistry for figuring out how to
harness that powerful immune system into a gene-editing tool called CRISPR/Cas9.
Here’s how it works: Scientists identify a section of DNA they want to alter,
create a short guide sequence that matches that DNA, and then CRISPR/Cas9
binds to that section and either cuts it out or activates specific genes.
It’s so precise that scientists can make multiple cuts to either remove a section
of DNA entirely or add new nucleotides. And so far, this system has been used to
make crops more resistant to disease, help people with sickle cell anemia, and more.
Thanks, Thought Bubble! At the time of this recording,
in 2023, medical treatments with CRISPR are still in clinical trials — it’s still very early days.
But if this system proves to be safe and effective,
it could make some genetic conditions a thing of the past.
Meanwhile, even just knowing what genes a person
has can help their doctor make more informed decisions about their health.
This personalized approach is called pharmacogenomics.
That word will get you 30 points in Scrabble, and it might also
help your doctor prescribe you the most effective treatments.
Pharmacogenomics is the study of how genes affect the way medicine
works — or the way your DNA influences how your body responds to certain drugs.
For instance, people often take aspirin to lower their risk of blood clots — and
by extension, strokes and heart attacks. But whether or not aspirin works for this
purpose depends on someone’s genes. So, by testing for certain mutations,
doctors can figure out if aspirin is the way to go, or if something else would be more effective.
At the end of the day, while it’s unlikely that a mutation is going to
give you telepathic abilities or the power to control static electricity,
they might give you a leg up on some everyday activities like drinking milk or sleeping.
And as for the mutations that cause harmful effects,
scientists are making breakthroughs on ways to reverse or even eliminate them.
So, while it’s unlikely we will ever get to just pick and choose our favorite mutations,
one thing is for sure: we all have them.
Ultimately, they’re just another aspect of life that connects us all.
Now as they say on TV, tune in next time for more thrilling adventures in Biology,
when we examine bacterial DNA! It’ll put a shock to your system!
This series was produced in collaboration with HHMI BioInteractive.
If you’re an educator, visit BioInteractive.org/CrashCourse for
classroom resources and professional development related to the topics covered in this course.
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in Indianapolis, Indiana, and was made with the help of all these nice people.
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