DNA is the most useful instruction manual in the world.

This special molecule   contains all the information needed to not only  make your body, but keep it running all your life.  And DNA does this job in every living  organism that we know of so far. But it’s even wilder than that.

Within those organisms are cells — trillions   of cells, in your case — that each need  their own copy of the instruction manual.  That’s a lot of toner. And the manual is massive.  If you were to print out the roughly 3 billion  letters of the genetic code stored in your DNA,   they would fill hundreds of thousands of pages.  You’ve got the most robust technical  library in the world inside of your body. Cells can read this manual cover to cover, but  for nearly all of scientific history, we couldn’t.  Until 2022, when — building on many decades  of progress — scientists finally produced the   first complete sequence of the human genome.

That means that they were able to document,   in order, the entire genetic  code that makes a human body. This major breakthrough could help  us understand all kinds of things,   like: What makes us similar to,  and distinct from, other species?  What makes some people respond  differently to certain medications?  And how can we treat diseases  like cancer more effectively? Hi!

I’m Dr. Sammy, your friendly neighborhood  entomologist, and this is Crash Course Biology.  Woof, so that was some pretty heavy stuff,  maybe some theme music could lighten the mood? [THEME MUSIC] So let’s begin with what DNA is made of: nucleotides, which are molecules  that consist of three parts. A sugar molecule.

A phosphate group, made from bonded phosphorus and oxygen atoms.  And one of four possible bases,  which all contain nitrogen.  We’ll get more into these  nucleotide bases in just a moment. But first, check this out: a bunch of these  nucleotides link up in a big conga line to   form DNA’s famous double helix shape. It looks kind of like a twisted ladder.  The rails on either side are the sugar-phosphate  backbones, named because they form the backbones   of DNA, and they’re made of chains of alternating  sugar and phosphate molecules of the nucleotides.

If you compared these two sugar-phosphate  chains side by side, you’d see that the one   on the left starts with a phosphate, and  the one on the right starts with a sugar.  It’s like one chain is upside-down. Biologists call these antiparallel strands.  And you’ll see how this mismatch  creates some shenanigans a little later. The rungs of this twisty funhouse ladder  are formed by DNA’s nucleotide bases,   which connect to the sugars in the backbones.  And when it comes to making DNA, your  cells have four bases to choose from.

The two largest are adenine and  guanine, or A and G for short.  The two smallest are thymine  and cytosine, or T and C. In a healthy strand of DNA, a big  base always connects with a small one,   using weak, chemical bonds called hydrogen bonds. To get even deeper: again in a healthy strand   of DNA, because of their structure,  adenine always bonds with thymine,   and guanine always bonds with cytosine.

A common way to remember this pairing is, “Apples   grow on trees” and “Cars go in the garage.” So, A goes with T and C goes with G. Now, here’s where it gets really interesting. Your cells use these bases — A, T, C,   and G — to store information.

In fact, these four letters make   up the whole alphabet of your genetic code. The specific order they fall into is what   allows your DNA to make you a human and  not another animal, like a chimpanzee. Throughout your DNA, these letters  are repeated over and over again,   in different combinations that form a  message more than three billion bases long.  Just four letters, in countless combinations.

All of this is packed up into chromosomes.  Chromosomes are chains of DNA molecules that  are coiled up tightly around special proteins   that help them fit inside the nucleus,  or control center, of each of your cells. And like I said at the top, almost every cell in  your body has a complete version of this code.  So that means that when you make new cells — and   your body is always making new  cells — they need a copy, too. That’s where DNA replication comes in.  And it’s where the structure of DNA really shines.  And all these details — the base pairs,  the twisting ladder — they aren’t random.  They all fit together in a precise way  that makes DNA replication possible.

At the beginning of this process,  an enzyme — or a substance that   helps trigger a chemical reaction  — splits the DNA ladder in half.  It breaks the hydrogen bonds connecting the base  pairs, and separates the two strands of DNA. Now, get ready: Your cell is about to turn these  half-strands into two complete strands of DNA.  And the amazing thing is, it already  has all the instructions it needs,   thanks to the specific order, or the  code, of all of those base pairs. DNA replication is done mostly by  an enzyme called DNA polymerase.  And when DNA polymerase rolls up to a half-strand  of DNA and sees a dangling adenine base, it knows   exactly what to do: It needs to attach a thymine.

Because remember, “apples grow on trees”. Then, if it sees a cytosine  hanging out on that half-strand,   it knows to attach a guanine  because “cars go in garages.” So, to copy DNA, this enzyme travels  up those half-strands and adds the   missing bases, plus sugar-phosphate  backbones, to complete the structure.  At the end of it all, boom: You have two full  strands of DNA, ready to go into new cells. Each new piece of DNA has just one  strand that’s newly constructed — pulled   together from nucleotides that were  floating around inside your body.  And a second strand that came  directly from the old molecule.  So, DNA replication is  considered semiconservative,   because the original strand of DNA is kept  partially the same in the new molecule.

And this is part of what makes DNA so useful. With just one strand — half a DNA molecule — cells   have all the information they  need to make more DNA molecules.  For a closer look at how this works,  let’s head over to the Thought Bubble. When it’s time for DNA replication, your cells   don’t unravel all of their coiled-up DNA at once.

If they did, you’d be left with   a chain of material taller than I am. And I’m pretty tall… so… okay I’m not, but still. So, instead, this process works in sections.

First, an enzyme called helicase unravels a   short stretch of DNA, creating  a bubble in the double helix.  This is a replication bubble, and  each end is a replication fork. Once the bubble is open, DNA polymerase steps in,  with one enzyme working on each unraveled strand.  One polymerase moves along the DNA in the  same direction as the helicase enzyme.  This polymerase is working on the leading  strand, which means its job is easy,   just attach complementary bases. A to T, C to G.

Meanwhile, the other polymerase is going in  the opposite direction, away from the helicase.  It’s working on the lagging strand. And its job is a bit harder.  See, DNA polymerase is only able to  add bases if it’s moving forward.  So, the polymerase on the lagging strand  ends up doing a bit of a weird dance.  It’s like it takes five steps forward, and then  adds five bases… and then jogs backward ten steps.  And then, it takes another five  steps forward to fill in the gap,   and then jogs backward ten more steps. That way, it can add bases in short   fragments as it moves forward.

These fragments are eventually   connected together into one, continuous  string with the help of yet another enzyme. Thanks, Thought Bubble! Now, DNA replication works   flawlessly almost all the time — which is  really incredible, when you think about it.  Somewhere in your body, cells  are dividing every second,   and they almost always get a  perfect copy of your genetic code.

But every now and then, something does go wrong.  For instance, a DNA polymerase might attach  a cytosine base to an adenine — it’ll try   to put a car… in an apple. Or grow an apple on a car.  Which really isn’t going to  work, however you say it. In other cases, damage from the environment —  like chemicals or a bad sunburn — might merge   base pairs together, or even  shift a big section of bases,   really throwing a wrench in DNA replication.

The good news is, your cells  are generally on top of this.  Enzymes keep close tabs on DNA replication,   double-checking what bases are added and making  sure that the process is happening correctly. When working properly, if they run  into a base that shouldn’t be there,   they’ll fix it, and get that car out of  the apple orchard and into the garage.  Sometimes, though, these errors aren’t caught,  and they make it into the new DNA strands.  From there, these errors can  get passed on to future cells,   or even to an organism’s future offspring. When this happens, it’s a mutation.

They’re not always as ominous as they sound, and   they don’t normally give you superpowers either. Some mutations can cause problems,   including cancer. But other mutations are totally neutral.

Like, blue eyes in humans. That was caused by one mutation in   a person who lived a few thousand years ago. Some mutations can even be helpful,   like the one that lets many adult  humans digest milk and cheese.  It all depends on what parts of  the genetic code get altered.

In any case, every living thing  — including you — acquires some   number of mutations during their lives. But our bodies are always fighting against them,   and usually, they’re pretty successful. In humans, DNA replication gets messed up   about once in every ten thousand  to one hundred thousand bases.  And after your cells proofread their work,  that rate goes down to one in ten billion.

So, how do we know all this stuff? It’s both too small for us to see without a   microscope and happening in too many billions of  different cells for us to track all the action.  Which is a huge part of what  makes DNA replication so amazing. Many, many scientists have   contributed — and are still contributing  — to our understanding of how DNA works.  But today, we’ll hang out with a particularly  special pair in the Theater of Life.  Dr.

Tsuneko and Dr. Reiji Okazaki  are Japanese molecular biologists.  In the 1960s, they wanted to find out more  about how exactly DNA replication happens. In one experiment, they added radioactive  molecules to a bunch of thymine bases.  They were basically hooking  them up with tracking devices,   so that they could follow the thymines as they  were added into the DNA of an E. coli bacterium.

The Okazakis and their team noticed that the  thymines were being added to DNA in short bursts,   only one to two thousand base pairs long. Then, those fragments were being strung   together into a much longer chain. If this sounds familiar, it's because   they were the first to observe what  was happening on the lagging strand!

At first, this process was so weird that other  scientists weren’t sure about the results.  So, the Okazakis kept on testing, to prove to the  scientific community that their data was right.  Sadly, Reiji never got to see that  recognition as he died of cancer in 1975.  The cancer was likely caused by radiation from  the nuclear bombing of Japan in World War II,   which might have disrupted DNA  replication in his own cells. In 1978, Tsuneko and her colleagues  presented enough data to validate   her and Reiji's work for good. And those short segments of DNA on   the lagging strand have been recognized  as “Okazaki fragments” ever since.

The structure of DNA is one of the big reasons that life  on Earth has gone so well.  With only a four-letter alphabet, DNA  contains all the information it takes   to make your body — or in other cases, to  make a mushroom, a bacterium, or a dolphin. And, all things considered, that code is fairly   straightforward to read and duplicate. Because certain bases always match up,   and your body only needs half a strand  of DNA to make a new, complete copy.  For as complex as life is, some things  about DNA are surprisingly simple!

Of course, just having a giant  instruction manual in your cells   isn’t enough to get your body to work. Next time, we’ll learn how cells translate   that manual into short, easy-to-follow  instructions that keep life on Earth going.  Peace! 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.

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.