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 three 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 uh 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 um maybe some theme music lighten the mood [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 congal 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 the phosphate and the one on the right starts with the sugar it's like one chain is upside down biologists call these anti-parallel 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 Adine and guanine or a and g for short the two smallest are thyine and cytosine or TN 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 Basse pairs the twisting ladder they aren't random they all fit together in a precise way that makes DNA replic a 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 thyine 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 bub when it's time for DNA replication your cells don't unravel all of their coil 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 dou 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 complimentary 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 it 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 10 steps and then it takes another five steps forward to fill in the Gap and then jogs backward 10 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 th 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 Adine 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 mut 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 10,000 to 100,000 bases and after your cells proofread their work that rate goes down to 1 in 10 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 that action which is a huge part of what makes DNA replication so amazing many 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 suo and Dr regi 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 thyine bases they were basically hooking them up with tracking devices so that they could follow the thines as they were added into the DNA of an ecoli bacteria the okazaki and their team notice that the Thymes were being added to DNA in short bursts only 1 to 2,000 base pairs long then those fragments were being strung together in 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 okazaki kept on testing to prove to the scientific community that their data was right sadly regie 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 suo and her colleagues presented enough data to validate her and R'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 of these these nice people if you want to help keep crash course free for everyone forever you can join our community on [Music] patreon