it's just beautiful, isn't it? it's just mesmerizing.it's double hel-exciting! you really can tell, just by looking at it,how important and amazing it is. it's pretty much the most complicated moleculethat exists, and potentially the most important one. it's so complex that we didn't even knowfor sure what it looked like until about 60 years ago. so multifariously awesome that if you tookall of it from just one of our cells and untangled it, it would be taller than me. now consider that there are probably 50 trillioncells in my body right now. laid end to end, the dna in those cells wouldstretch to the sun.
not once... but 600 times! mind blown yet? hey, you wanna make one? (oh dear god) of course you know i'm talking about deoxyribonucleicacid, known to its friends as dna. dna is what stores our genetic instructions-- the information that programs all of our cell's activities. it's a 6-billion letter code that providesthe assembly instructions for everything that you are.
and it does the same thing for pretty muchevery other living thing. i'm going to go out on a limb and assumeyou're human. in which case every body cell, or somaticcell, in you right now, has 46 chromosomes each containing one big dna molecule. these chromosomes are packed together tightlywith proteins in the nucleus of the cell. dna is a nucleic acid. and so is its cousin, which we'll also betalking about, ribonucleic acid, or rna. now if you can make your mind do this, rememberall the way back to episode 3, where we talked about all the important biological molecules:
carbohydrates, lipids and proteins. that ringa bell? well nucleic acids are the fourth major groupof biological molecules, and for my money they have the most complicated job of all. structurally they're polymers, which meansthat each one is made up of many small, repeating molecular units. in dna, these small units are called nucleotides.link them together and you have yourself a polynucleotide. now before we actually put these tiny partstogether to build a dna molecule like some microscopic piece ofikea furniture, let's
first take a look at what makes up each nucleotide. we're gonna need three things: 1. a five-carbon sugar molecule 2. a phosphate group 3. one of four nitrogen bases dna gets the first part its name from ourfirst ingredient, the sugar molecule, which is called deoxyribose. but all the really significant stuff, thegenetic coding that makes you you, is found among the four nitrogenous bases:
adenine (a), thymine (t), cytosine (c) andguanine (g). it's important to note that in living organisms,dna doesn't exist as a single polynucleotide molecule, but rathera pair of molecules that are held tightly together. they're like an intertwined, microscopic,double spiral staircase. basically, just a ladder, but twisted. thefamous double helix. and like any good structure, we have to havea main support. in dna, the sugars and phosphates bond togetherto form twin backbones. these sugar-phosphate bonds run down eachside of the helix but, chemically, in opposite directions.
in other words, if you look at each of thesugar-phosphate backbones, you'll see that one appears upside-down in relation to theother. one strand begins at the top with the firstphosphate connected to the sugar molecule's 5th carbon and then ending where the nextphosphate would go, with a free end at the sugar's 3rd carbon. this creates a pattern called 5' (5 prime)and 3' (3 prime). i've always thought of the deoxyribose withan arrow, with the oxygen as the point. it always 'points' from from 3' to 5'.
now on the other strand, it's exactly theopposite. it begins up top with a free end at the sugar's3rd carbon and the phosphates connect to the sugars' fifth carbons all the way down. and it ends at the bottom with a phosphate. and you've probably figured this out already,but this is called the 3' to 5' direction. now it is time to make ourselves one of thesefamous double helices. these two long chains are linked by the nitrogenousbases via relatively weak hydrogen bonds. but they can't be just any pair of nitrogenousbases. thankfully, when it comes to figuring outwhat part goes where, all you have to do is
remember is that if one nucleotide has anadenine base (a), only thymine (t) can be its counterpart (a-t). likewise, guanine (g) can only bond with cytosine[c] (g-c). these bonded nitrogenous bases are calledbase pairs. the g-c pairing has three hydrogen bonds,making it slightly stronger than the a-t base-pair, which only has two bonds. it's the order of these four nucleobasesor the base sequence that allows your dna to create you. so, aggtccatg means something completely differentas a base sequence than, say, ttcagtcg.
human chromosome 1, the largest of all ourchromosomes, contains a single molecule of dna with 247 million base pairs. if you printed all of the letters of chromosome1 into a book, it would be about 200,000 pages and each of your somatic cells has 46 dnamolecules tightly packed into its nucleus -- that's one for each of your chromosomes. put all 46 molecules together and we'retalking about roughly 6 billion base pairs .... in every cell! this is the longest book i've ever read. it's about 1,000 pages long.
if we were to fill it with our dna sequence,we'd need about 10,000 of them to fit our entire genome. pop quiz!!! let's test your skills using a very shortstrand of dna. i'll give you one base sequence -- yougive me the base sequence that appears on the other strand. okay, here goes: 5' -- aggtccg -- 3' and... time's up.
the answer is: 3' -- tccaggc -- 5' see how that works? it's not super complicated. since each nitrogenous base only has one counterpart,you can use one base sequence to predict what its matching sequence is going to look like. so could i make the same base sequence witha strand of that "other" nucleic acid, rna? no, you could not. rna is certainly similar to its cousin dna-- it has a sugar-phosphate backbone with
nucleotide bases attached to it. but there are three major differences: 1. rna is a single-stranded molecule -- nodouble helix here. 2. the sugar in rna is ribose, which has onemore oxygen atom than deoxyribose, hence the whole starting with an r instead of a d thing. 3. also, rna does not contain thymine. itsfourth nucleotide is the base uracil, so it bonds with adenine instead. rna is super important in the production ofour proteins, and you'll see later that it has a crucial role in the replication ofdna.
but first... biolo-graphies! yes, plural this week! because when you start talking about somethingas multitudinously awesome and elegant as dna, you have to wonder: who figured all of this out? and how big was their brain? well unsurprisingly, it actually took a lotof different brains, in a lot of different countries
and nearly a hundred years of thinking todo it. the names you usually hear when someone askswho discovered dna are james watson and francis crick. but that's bunk. they did not discover dna. nor did they discover that dna contained geneticinformation. dna itself was discovered in 1869 by a swissbiologist named friedrich miescher. his deal was studying white blood cells. and he got those white blood cells in themost horrible way you could possibly imagine, from collecting used bandages from a nearbyhospital.
it's for science he did it! he bathed the cells in warm alcohol to removethe lipids, then he set enzymes loose on them to digestthe proteins. what was left, after all that, was snottygray stuff that he knew must be some new kind of biological substance. he called it nuclein, but was later to becomeknown as nucleic acid. but miescher didn't know what its role wasor what it looked like. one of those scientists who helped figurethat out was rosalind franklin, a young biophysicist in london nearly a hundred years later.
using a technique called x-ray diffraction,franklin may have been the first to confirm the helical structure of dna. she also figured out that the sugar-phosphatebackbone existed on the outside of its structure. so why is rosalind franklin not exactly ahousehold name? two reasons: 1. unlike watson & crick, franklin was happyto share data with her rivals. it was franklin who informed watson & crick that an earliertheory of a triple-helix structure was not possible,and in doing so she indicated that dna may indeed be a double helix. later, her images confirming the helical structureof dna were shown to watson without her knowledge.
her work was eventually published in nature,but not until after two papers by watson and crick had already appeared in which the duoonly hinted at her contribution. 2. even worse than that, the nobel prize committeecouldn't even consider her for the prize that they awarded in 1962 because of how deadshe was. the really tragic thing is that it's totallypossible that her scientific work may have led to her early death of ovarian cancer atthe age of 37. at the time, the x-ray diffraction technologythat she was using to photograph dna required dangerous amounts of radiation exposure, andfranklin rarely took precautions to protect herself. nobel prizes cannot be awarded posthumously.many believe she would have shared watson
and crick's medal if she had been aliveto receive it. now that we know the basics of dna's structure,we need to understand how it copies itself, because cells are constantly dividing, andthat requires a complete copy of all of that dna information. it turns out that our cells are extremelygood at this -- our cells can create the equivalent 10,000 copies of this book in justa few hours. that, my friends, is called replication. every cell in your body has a copy of thesame dna. it started from an original copy and it will copy itself trillions of timesover the course of a lifetime, each time using
half of the original dna strand as a templateto build a new molecule. so, how is a teenage boy like the enzyme helicase? they both want to unzip your genes. (hank why) helicase is marvelous, unwinding the doublehelix at breakneck speeds, slicing open those loose hydrogen bonds between the base pairs. the point where the splitting starts is knownas the replication fork, has a top strand, called the leading strand, or the good guystrand as i call it and another bottom strand called the laggingstrand, which i like to call the scumbag strand, because it is a pain in the butt to deal with.
these unwound sections can now be used astemplates to create two complementary dna strands. but remember the two strands go in oppositedirections, in terms of their chemical structure, which means making a new dna strand for theleading strand is going to be much easier for the lagging strand. for the leading, good guy, strand an enzymecalled dna polymerase just adds matching nucleotides onto the main stem all the way down the molecule. but before it can do that it needs a sectionof nucleotides that fill in the section that's just been unzipped. starting at the very beginning of the dnamolecule, dna polymerase needs a bit of a
primer, just a little thing for it to hookon to so that it can start building the new dna chain. and for that little primer, we can thank theenzyme rna primase. the leading strand only needs this rna primeronce at the very beginning. then dna polymerase is all, "i got this" and just follows the unzipping, adding newnucleotides to the new chain continuously, all the way down the molecule. copying the lagging, or scumbag strand, is, well, he's a freaking scumbag.
this is because dna polymerase can only copystrands in the 5' -- 3' direction, and the lagging strand is 3' -- 5', so dna polymerase can only add new nucleotidesto the free, 3' end of a primer. so maybe the real scumbag here is the dnapolymerase. since the lagging strand runs in the oppositedirection, it has to be copied as a series of segments. here that awesome little enzyme rna primasedoes its thing again, laying down an occasional short little rna primer that gives the dnapolymerase a starting point to then work backwards along the strand.
this is done in a ton of individual segments,each 1,000 to 2,000 base pairs long and each starting with an rna primer, called okazakifragments after the couple of married scientists who discovered this step of the process inthe 1960s. and thank goodness they were married so wecan just call them okazaki fragments instead of okazaki-someone's-someone fragments. these allow the strands to be synthesizedin short bursts. then another kind of dna polymerase has togo back over and replace all those rna primers and then all of the little fragments get joinedup by a final enzyme called dna ligase. and that is why i saythe lagging strand is such a scumbag!
dna replication gets it wrong about one inevery 10 billion nucleotides. but don't think your body doesn't havean app for that! it turns out dna polymerases can also proofread,in a sense, removing nucleotides from the end of a strandwhen they discover a mismatched base. because the last thing we want is an a whenit would have been a g! considering how tightly packed dna is intoeach one of our cells, it's honestly amazing that more mistakes don't happen. remember, we're talking about millions ofmiles worth of this stuff inside us. and this, my friends, is why scientists arenot exaggerating when they call dna the most
celebrated molecule of all time. so, you might as well look this episode overa couple of times and appreciate it for yourself. and in the mean time, gear up for next week,when we're going to talk about how those six feet of kick-ass actually makes you, you. thank you to all the people here at crashcourse who helped make this episode awesome. you can click on any of these things to goback to that section of the video. if you have any questions, please, of course,ask them in the comments or on facebook or twitter.
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