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Science fiction is full of superpowered mutants, but in reality, mutations are much more diverse and complex. Sometimes, they can change someone’s entire body, and other times, we don’t notice them at all! In this episode, we’ll unpack what mutations are, how they work (including substitutions and frameshift mutations), and how scientists are learning to control mutations using tools like CRISPR/Cas9 and gene therapy.

Introduction: Mutations Outside the Movies
What Are Mutations?
What Determines Mutations' Effects?
Types of Mutations
Positive, Negative, or Neutral?
Gene Therapy & CRISPR
Review & Credits

This series was produced in collaboration with HHMI BioInteractive, committed to empowering educators and inspiring students with engaging, accessible, and quality classroom resources. Visit for more information.

Check out our Biology playlist here:

Watch this series in Spanish on our Crash Course en Español channel here:

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 for   classroom resources and professional development  related to the topics covered in this course. Thanks for watching this episode of Crash  Course Biology which was filmed at our studio   in Indianapolis, Indiana, and was made  with the help of all these nice people.  If you want to help keep Crash  Course free for everyone,   forever, you can join our community on Patreon.