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  • 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 molecule that exists, and potentially the most important one.

  • It's so complex that we didn't even know for sure what it looked like

  • until about 60 years ago.

  • So multifariously awesome that if you took all of it from just one of our cells and untangled it,

  • it would be taller than me.

  • Now consider that there are probably 50 trillion cells in my body right now.

  • Laid end to end, the DNA in those cells would stretch to the sun.

  • Not once...

  • but 600 times!

  • Mind blown yet?

  • Hey, you wanna make one?

  • Of course you know I'm talking about deoxyribonucleic acid, 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 provides the assembly instructions for everything that

  • you are.

  • And it does the same thing for pretty much every other living thing.

  • I'm going to go out on a limb and assume you're human.

  • In which case every body cell, or somatic cell, in you right now, has 46

  • chromosomes each containing one big DNA molecule.

  • These chromosomes are packed together tightly with proteins in the nucleus of the cell.

  • DNA is a nucleic acid.

  • And so is its cousin, which we'll also be talking about, ribonucleic acid, or RNA.

  • Now if you can make your mind do this, remember all the way back to episode 3, where we talked

  • about all the important biological molecules:

  • carbohydrates, lipids and proteins. That ring a bell?

  • Well nucleic acids are the fourth major group of biological molecules, and for my money

  • they have the most complicated job of all.

  • Structurally they're polymers, which means that 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 parts together to build a

  • DNA molecule like some microscopic piece of Ikea 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 our first ingredient, the sugar

  • molecule, which is called deoxyribose.

  • But all the really significant stuff, the genetic coding that makes you YOU,

  • is found among the four nitrogenous bases:

  • adenine (A), thymine (T), cytosine (C) and guanine (G).

  • It's important to note that in living organisms, DNA doesn't exist

  • as a single polynucleotide molecule, but rather a pair of molecules that

  • are held tightly together.

  • They're like an intertwined, microscopic, double spiral staircase.

  • Basically, just a ladder, but twisted. The famous Double Helix.

  • And like any good structure, we have to have a main support.

  • In DNA, the sugars and phosphates bond together to form twin backbones.

  • These sugar-phosphate bonds run down each side of the helix but, chemically, in opposite directions.

  • In other words, if you look at each of the sugar-phosphate backbones, you'll see that

  • one appears upside-down in relation to the other.

  • One strand begins at the top with the first phosphate connected to the sugar molecule's

  • 5th carbon and then ending where the next phosphate 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 with an arrow, with the oxygen as the point.

  • It always 'points' from from 3' to 5'.

  • Now on the other strand, it's exactly the opposite.

  • It begins up top with a free end at the sugar's 3rd 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 these famous double helices.

  • These two long chains are linked by the nitrogenous bases via relatively weak hydrogen bonds.

  • But they can't be just any pair of nitrogenous bases.

  • Thankfully, when it comes to figuring out what part goes where, all you have to do is

  • remember is that if one nucleotide has an adenine 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 called base 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 nucleobases or the Base Sequence that allows your DNA

  • to create you.

  • So, AGGTCCATG means something completely different as a base sequence than, say, TTCAGTCG.

  • Human chromosome 1, the largest of all our chromosomes, contains a single molecule of

  • DNA with 247 million base pairs.

  • If you printed all of the letters of chromosome 1 into a book, it would be about 200,000 pages

  • long.

  • And each of your somatic cells has 46 DNA molecules tightly packed into its nucleus

  • -- that's one for each of your chromosomes.

  • Put all 46 molecules together and we're talking 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 short strand of DNA.

  • I'll give you one base sequence -- you give 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 with a 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 -- no double helix here.

  • 2. The sugar in RNA is ribose, which has one more oxygen atom than deoxyribose, hence the

  • whole starting with an R instead of a D thing.

  • 3. Also, RNA does not contain thymine. Its fourth nucleotide is the base uracil, so it

  • bonds with adenine instead.

  • RNA is super important in the production of our proteins, and you'll see later that

  • it has a crucial role in the replication of DNA.

  • But first...

  • Biolo-graphies!

  • Yes, plural this week!

  • Because when you start talking about something as 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 lot of different brains, in a lot of different

  • countries

  • and nearly a hundred years of thinking to do it.

  • The names you usually hear when someone asks who discovered DNA are James Watson and Francis

  • Crick.

  • But that's BUNK. They did not discover DNA.

  • Nor did they discover that DNA contained genetic information.

  • DNA itself was discovered in 1869 by a Swiss biologist named Friedrich Miescher.

  • His deal was studying white blood cells.

  • And he got those white blood cells in the most horrible way you could possibly imagine,

  • from collecting used bandages from a nearby hospital.

  • It's for science he did it!

  • He bathed the cells in warm alcohol to remove the lipids,

  • then he set enzymes loose on them to digest the proteins.

  • What was left, after all that, was snotty gray stuff that he knew must be some new kind

  • of biological substance.

  • He called it nuclein, but was later to become known as nucleic acid.

  • But Miescher didn't know what its role was or what it looked like.

  • One of those scientists who helped figure that 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-phosphate backbone existed on the outside of its structure.

  • So why is Rosalind Franklin not exactly a household name? Two reasons:

  • 1. Unlike Watson & Crick, Franklin was happy to share data with her rivals. It was Franklin

  • who informed Watson & Crick that an earlier theory

  • 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 structure of 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 duo only hinted at her contribution.

  • 2. Even worse than that, the Nobel Prize Committee couldn't even consider her for the prize

  • that they awarded in 1962 because of how dead she was.

  • The really tragic thing is that it's totally possible that her scientific work may have

  • led to her early death of ovarian cancer at the age of 37.

  • At the time, the X-Ray diffraction technology that she was using to photograph DNA required

  • dangerous amounts of radiation exposure, and Franklin 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 alive to 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, and that requires a complete copy of all of that

  • DNA information.

  • It turns out that our cells are extremely good at this -- our cells can create the

  • equivalent 10,000 copies of this book in just a few hours.

  • That, my friends, is called replication.

  • Every cell in your body has a copy of the same DNA. It started from an original copy

  • and it will copy itself trillions of times over the course of a lifetime, each time using

  • half of the original DNA strand as a template to build a new molecule.

  • So, how is a teenage boy like the enzyme Helicase?

  • They both want to unzip your genes.

  • Helicase is marvelous, unwinding the double helix at breakneck speeds, slicing open those

  • loose hydrogen bonds between the base pairs.

  • The point where the splitting starts is known as the replication fork, has a top strand,

  • called the leading strand, or the good guy strand as I call it

  • and another bottom strand called the lagging strand, 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 as templates to create two complementary DNA strands.

  • But remember the two strands go in opposite directions, in terms of their chemical structure,

  • which means making a new DNA strand for the leading strand is going to be much easier

  • for the lagging strand.

  • For the leading, good guy, strand an enzyme called 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 section of nucleotides that fill in the section that's

  • just been unzipped.

  • Starting at the very beginning of the DNA molecule, DNA polymerase needs a bit of a

  • primer, just a little thing for it to hook on to so that it can start building the new

  • DNA chain.

  • And for that little primer, we can thank the enzyme RNA primase.

  • The leading strand only needs this RNA primer once at the very beginning.

  • Then DNA polymerase is all, "I got this"

  • and just follows the unzipping, adding new nucleotides 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 copy strands in the 5' -- 3' direction,

  • and the lagging strand is 3' -- 5',

  • so DNA polymerase can only add new nucleotides to the free, 3' end of a primer.

  • So maybe the real scumbag here is the DNA polymerase.

  • Since the lagging strand runs in the opposite direction, it has to be copied as a series

  • of segments.

  • Here that awesome little enzyme RNA Primase does its thing again, laying down an occasional

  • short little RNA primer that gives the DNA Polymerase 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 Okazaki fragments after the couple of married scientists

  • who discovered this step of the process in the 1960s.

  • And thank goodness they were married so we can just call them Okazaki fragments instead

  • of Okazaki-someone's-someone fragments.

  • These allow the strands to be synthesized in short bursts.

  • Then another kind of DNA Polymerase has to go back over and replace all those RNA Primers

  • and THEN all of the little fragments get joined up by a final enzyme called DNA Ligase. And

  • that is why I say the lagging strand is such a scumbag!

  • DNA replication gets it wrong about one in every 10 billion nucleotides.

  • But don't think your body doesn't have an app for that!

  • It turns out DNA polymerases can also proofread, in a sense,

  • removing nucleotides from the end of a strand when they discover a mismatched base.

  • Because the last thing we want is an A when it would have been a G!

  • Considering how tightly packed DNA is into each one of our cells, it's honestly amazing

  • that more mistakes don't happen.

  • Remember, we're talking about millions of miles worth of this stuff inside us.

  • And this, my friends, is why scientists are not exaggerating when they call DNA the most

  • celebrated molecule of all time.

  • So, you might as well look this episode over a 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 Crash Course who helped make this episode awesome.

  • You can click on any of these things to go back to that section of the video.

  • If you have any questions, please, of course, ask them in the comments or on Facebook or Twitter.

It's just beautiful, isn't it? It's just mesmerizing. It's double hel-exciting!

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DNAの構造と複製。クラッシュコース生物学 #10 (DNA Structure and Replication: Crash Course Biology #10)

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    Chi-feng Liu に公開 2021 年 01 月 14 日
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