DNA Structure and Replication: Crash Course Biology #10

Summary

Este video ofrece una explicación fascinante sobre el ADN, su estructura de doble hélice, y su importancia en la codificación genética. Desde la historia del descubrimiento del ADN hasta su papel en la replicación celular, el video describe cómo los nucleótidos forman secuencias de bases, y cómo estas determinan nuestras características biológicas. También se destacan las diferencias entre el ADN y el ARN, el proceso de replicación y la contribución de científicos como Rosalind Franklin, James Watson y Francis Crick. Todo esto es presentado de manera entretenida y educativa.

Takeaways

• 🌟 El ADN es una molécula de doble helix increíblemente compleja y esencial para la vida, almacenando las instrucciones genéticas en nuestras células.
• 🧬 Cada célula en el cuerpo humano contiene aproximadamente 46 cromosomas, cada uno con un gran molécula de ADN.
• 🔬 El descubrimiento y la estructura del ADN fue un logro colectivo de muchos científicos a lo largo de casi un siglo.
• 🏆 Rosalind Franklin fue una científica clave en la comprensión de la estructura del ADN, utilizando la difracción de rayos X.
• 🔋 El ADN se compone de azúcares, fosfatos y bases nitrogenadas, y se organiza en una doble helix con base pares específicos (A-T y G-C).
• 🧵 La replicación del ADN es un proceso preciso y rápido que permite a las células dividirse y transmitir la información genética a nuevas células.
• 🔄 La enzima Helicasa desempeña un papel crucial al 'deszipar' la doble helix del ADN, preparándolo para la replicación.
• 🧩 La replicación del ADN en la cadena 'buena' (cadena dirigente) es directa, mientras que la cadena 'mala' (cadena retardada) requiere de fragmentos Okazaki y una serie de enzimas para completarse.
• 🛠 Las enzimas de la replicación del ADN también tienen la capacidad de corregir errores, asegurando la precisión en la copia del código genético.
• 🧬 El ADN es considerado la molécula más importante y celebrada debido a su papel central en la herencia genética y la diversidad biológica.

Q & A

¿Qué es la molécula de ADN y por qué es importante?

El ADN, o ácido desoxirribonucleico, es una molécula compleja que almacena las instrucciones genéticas que programan las actividades de todas nuestras células y de la mayoría de los seres vivos. Es crucial ya que contiene el código de seis mil millones de letras que proporciona las instrucciones para construir a cada individuo.

¿Cuál fue el papel de Rosalind Franklin en el descubrimiento de la estructura del ADN?

Rosalind Franklin utilizó la difracción de rayos X para confirmar la estructura helical del ADN y determinar que el backbone de azúcar y fosfato estaba en el exterior. A pesar de su contribución significativa, su trabajo no fue reconocido de manera justa en su tiempo debido a la falta de crédito y su fallecimiento prematuro.

¿Cómo se replica el ADN durante la división celular?

El ADN se replica a través de un proceso llamado 'fork de replicación', donde la enzima Helicasa desenrolla el helix doble y la enzima DNA Polimerasa utiliza las cadenas desenrolladas como plantillas para construir nuevas cadenas de ADN complementarias.

¿Qué es una base par en el ADN y cuáles son las dos parejas de bases permitidas?

Una base par en el ADN es una unión específica entre dos bases nitrogenadas que se encuentran en cadenas opuestas del helix. Las dos parejas de bases permitidas son adenina (A) con timina (T) y guanina (G) con citosina (C).

¿Cuál es la diferencia entre la cadena 'good guy' y la cadena 'scumbag' en la replicación del ADN?

La cadena 'good guy', o cadena líder, se replica de manera continua y directa, mientras que la cadena 'scumbag', o cadena rezagada, se replica en segmentos discontinuos debido a la dirección opuesta de la cadena y la necesidad de utilizar múltiples primarios RNA para iniciar la síntesis.

¿Cómo se llaman los fragmentos de ADN que se sintetizan durante la replicación de la cadena rezagada?

Los fragmentos de ADN que se sintetizan durante la replicación de la cadena rezagada se llaman fragmentos de Okazaki, nombrados en honor a los científicos japoneses Reiji y Tsuneko Okazaki, quienes descubrieron este paso del proceso.

¿Qué es la enzima Helicasa y qué hace durante la replicación del ADN?

La enzima Helicasa desenrolla el helix doble del ADN rompiendo las débiles enlaces de hidrógeno entre las bases pares, preparando así las cadenas para ser usadas como plantillas en la síntesis de nuevas cadenas de ADN.

¿Cómo se corrige un error durante la replicación del ADN?

Los errores durante la replicación del ADN son corregidos por la capacidad de 'proofread' de las enzimas DNA Polimerasas, que pueden eliminar nucleótidos si detectan una base no emparejada y reemplazarla por la correcta.

¿Cuál es la importancia de la molécula de RNA en comparación con el ADN?

La molécula de RNA, aunque similar al ADN, es una molécula de una sola cadena y utiliza uracilo en lugar de timina. Es crucial en la síntesis de proteínas y en la replicación del ADN, actuando como intermediario en la traducción del código genético en proteínas.

¿Por qué no se puede utilizar una cadena de RNA para replicar una cadena de ADN con la misma secuencia?

No se puede utilizar una cadena de RNA para replicar una cadena de ADN directamente debido a las diferencias en la estructura y las bases nitrogenadas. El ADN tiene un par de bases específico (A-T y G-C), mientras que el RNA utiliza adenina (A) con uracilo (U) en lugar de timina (T).

Outlines

00:00

🧬 La Molécula del ADN

El primer párrafo introduce al ADN como una molécula extraordinariamente compleja y vital, la cual contiene las instrucciones genéticas de todos los seres vivos. Se menciona su apariencia como una doble hélice y cómo, hasta hace 60 años, no se conocía su estructura exacta. El ADN se compone de 46 cromosomas en las células humanas, y si se desenredaran, serían más largos que el trayecto a Marte. Se explica que el ADN está formado por nucleótidos, que a su vez están compuestos por un azúcar de cinco carbonos (desoxirribosa), un grupo fosfato y una de cuatro bases nitrogenadas (adenina, timina, citosina y guanina). Estas bases se unen específicamente para formar pares base, donde la adenina se une a la timina y la guanina a la citosina, manteniendo la estructura de la doble hélice.

05:01

🔬 La Replicación del ADN y su Historia

Este párrafo se centra en la replicación del ADN, esencial para la división celular y la transmisión de información genética. Se describe el proceso de replicación como una tarea compleja y precisa, donde las helicases desdoblan la doble hélice y el ADN se copia utilizando la mitad original como plantilla para construir una nueva molécula. Se menciona la diferencia entre el estrándago líder y el estrándago lagging, y cómo se enfrentan a los desafíos de la replicación. Además, se aborda la historia del descubrimiento del ADN, reconociendo no solo a Watson y Crick sino también a Rosalind Franklin y otros científicos que contribuyeron a comprender su estructura y función. Se destaca la importancia de Franklin en particular, cuyos descubrimientos fueron fundamentales pero no fueron reconocidos de manera justa.

10:03

🧐 Detalles del Proceso de Replicación del ADN

El tercer párrafo profundiza en los detalles del proceso de replicación del ADN, explicando cómo las enzimas como la helicase y la DNA polymerase trabajan para desenredar y construir nuevas cadenas de ADN. Se discute cómo se requiere un primero de RNA para iniciar la síntesis de la cadena del estrándago líder, mientras que el estrándago lagging requiere múltiples primers de RNA para construir fragmentos más cortos conocidos como fragmentos de Okazaki. Finalmente, se menciona la corrección de errores por parte de la DNA polymerase, lo que asegura la precisión en la replicación del ADN. El párrafo concluye con un reconocimiento del ADN como la molécula más celebrada de todos los tiempos y un llamado a la acción para que el espectador revise el material y se prepare para el próximo tema, que se enfocará en cómo el ADN da lugar a la individualidad humana.

Keywords

💡Ácido desoxirribonucleico (ADN)

El ADN es una molécula compleja que contiene las instrucciones genéticas para el desarrollo y funcionamiento de los seres vivos. En el video, se describe como una doble hélice formada por nucleótidos, cuya secuencia determina las características de un organismo. Es esencial para la replicación celular y la herencia genética.

💡Nucleótido

Un nucleótido es la unidad básica que forma el ADN. Está compuesto por un azúcar de cinco carbonos (desoxirribosa en el ADN), un grupo fosfato y una base nitrogenada. Los nucleótidos se enlazan entre sí para formar largas cadenas que componen el ADN. En el video, se mencionan como bloques fundamentales para construir la molécula de ADN.

💡Bases nitrogenadas

Las bases nitrogenadas en el ADN son adenina (A), timina (T), citosina (C) y guanina (G). Estas bases se emparejan de manera específica: A con T, y C con G, a través de enlaces de hidrógeno. La secuencia de estas bases es lo que codifica la información genética. El video destaca cómo estas bases forman pares y crean la estructura de doble hélice del ADN.

💡Doble hélice

La doble hélice es la estructura tridimensional del ADN, compuesta por dos cadenas de nucleótidos enrolladas entre sí. Esta estructura fue confirmada por el trabajo de científicos como Rosalind Franklin. En el video, se compara la doble hélice con una escalera en espiral, donde los peldaños son los pares de bases nitrogenadas y las barandillas son los azúcares y fosfatos.

💡Replicación del ADN

La replicación del ADN es el proceso mediante el cual una célula copia su ADN antes de dividirse. Durante este proceso, las dos hebras de la doble hélice se separan y se utilizan como plantillas para formar nuevas hebras complementarias. En el video, se explica cómo las enzimas, como la helicasa y la ADN polimerasa, juegan un papel clave en este proceso.

💡Enzima helicasa

La helicasa es una enzima que desenrolla la doble hélice del ADN, separando las dos cadenas para que puedan replicarse. El video la describe humorísticamente comparándola con un adolescente que 'quiere desabrochar tus genes'. Su función es crucial para iniciar el proceso de replicación del ADN, creando la horquilla de replicación.

💡Polimerasa de ADN

La ADN polimerasa es una enzima que añade nucleótidos complementarios a una cadena de ADN durante la replicación. Esta enzima trabaja en la dirección 5' a 3', lo que facilita la replicación de la hebra líder, pero complica la de la hebra rezagada. El video menciona que también realiza una función de 'corrección de pruebas' para evitar errores en la secuencia de bases.

💡Horquilla de replicación

La horquilla de replicación es la región donde el ADN se desenrolla para ser replicado. En esta zona, la helicasa separa las hebras de ADN, permitiendo que otras enzimas como la ADN polimerasa comiencen a copiar las hebras. El video describe cómo este proceso da lugar a una hebra líder que se copia fácilmente y una hebra rezagada que requiere más pasos.

💡Hebra líder

La hebra líder es la cadena de ADN que se replica de manera continua en la dirección 5' a 3', gracias a la acción de la ADN polimerasa. En el video, se describe como la 'buena' hebra que se copia sin problemas a medida que la helicasa desenrolla el ADN, a diferencia de la hebra rezagada.

💡Fragmentos de Okazaki

Los fragmentos de Okazaki son pequeñas secuencias de ADN que se forman en la hebra rezagada durante la replicación. Debido a que la ADN polimerasa solo puede sintetizar ADN en una dirección (5' a 3'), la hebra rezagada se copia en segmentos cortos. El video menciona estos fragmentos como un paso necesario para completar la replicación de la hebra rezagada.

Highlights

DNA is the most complex and important molecule, essential for life.

DNA was discovered by Friedrich Miescher in 1869, not by Watson and Crick.

The structure of DNA is a double helix, confirmed by Rosalind Franklin's X-ray diffraction.

DNA is a nucleic acid that contains a 6-billion-letter code that programs the cell's activities.

Each somatic cell in the human body contains 46 chromosomes, each with a large DNA molecule.

DNA is made of nucleotides consisting of a five-carbon sugar, a phosphate group, and one of four nitrogenous bases: adenine, thymine, cytosine, and guanine.

Adenine always pairs with thymine, and guanine always pairs with cytosine in DNA.

If untangled, the DNA from a single cell would be taller than a human.

The DNA from all the cells in the human body could stretch to the sun and back 600 times.

Human chromosome 1 contains 247 million base pairs.

RNA is similar to DNA but has three key differences: it's single-stranded, has ribose sugar, and uses uracil instead of thymine.

Rosalind Franklin's work was critical in discovering the double helix structure of DNA, but she didn't receive the recognition she deserved.

DNA polymerase adds nucleotides to a new DNA strand during replication, but RNA primase provides the initial primer.

Replication errors occur once in every 10 billion nucleotides, but DNA polymerases can proofread and fix errors.

The lagging strand in DNA replication is copied in fragments called Okazaki fragments, named after the scientists who discovered them.

Transcripts

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? (oh dear god)

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

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. (Hank why)

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.