[Instructor] Hello
and welcome to the second lecture in Module 2,
and this lecture is called DNA Structure.
Okay, are you ready to go?
Are you pumped? You psyched?
Yeah, we're ready to talk about structure, molecules?
Excellent.
Well, what I promise you is that I will try my best
to make this as painless as possible
and to boil it down really to what are the key and critical,
most important points that I'd like you to know
in order to build off of that
for what we will learn and explore and find applications for
later on in this course.
So let's get started.
A few points on some basics of genetics
that I want to make sure is clear before we move ahead
because I think these points are absolutely critical,
but can are very often confused in,
I find if I'm reading say, you know, a newspaper article
or something like that on genetics, that many times
the information on some of these basic aspects of genetics
can be incorrect.
And I think that's very common
that there are some misunderstandings
that are important to address
before we move on into some of the details of genetics.
So just to start with a few definitions.
Genetics is the study of the general mechanisms of heredity
and the variation of inherited traits,
typically one gene at a time.
So what do I mean by this?
Well first of all, let me just step back and say
I'm defining genetics, I'm defining genomics
and this is the title of the course.
But I think it's important to define both of these
because they can be overlapping
and sometimes they're used interchangeably,
but they actually do have
two slightly different definitions.
So when we're talking about genetics,
this is really more just the general mechanisms of heredity,
how are traits passed on,
and it may be looking one gene at a time.
This would be, for example,
looking at the gene that is related to cystic fibrosis.
So if you're just studying that one gene
and looking at the influence it has on a particular trait,
that would be really the study of genetics.
If however you are, say, starting with a disease
that you don't know what the genetic aspect of it is,
you don't understand,
there isn't clear which particular gene or genes
would influence it.
And you're utilizing tools like whole genome sequencing
where you're going to find out
all the information about an individual
and you're going to start to work to better understand
how all genes and their interrelationships
are going to influence this particular trait
that you're interested in.
All right, so the other term
that's very important to understand is gene.
Gene is the unit of inheritance
and we'll talk more about what that actually means later.
But basically one gene provides the instructions
for making one particular type of protein.
So one gene equals one protein for the most part.
Again, here comes my standard disclaimer,
but there are certainly exceptions to that
because we do actually have more different types of proteins
than we have different types of genes.
And there are lots of reasons for that
and that gets to become,
that starts to become quite complicated
to describe and understand, so we'll just think about it
more from the majority rule here.
The majority rule is
that one gene provides instructions for making one protein
and that's how a gene is defined.
It's defined as a segment long DNA
that encodes or provides the instructions
for one specific protein,
and proteins perform functions within cells, tissues, organs
in the whole system.
And I know you're familiar with proteins.
I've provided one here.
Insulin is an example of a protein but there are,
I mean tens of thousands more than that
of different proteins in the human body.
And I'm sure you're familiar with, you know,
maybe monitoring certain levels of,
monitoring levels of certain proteins
which may indicate how well a patient is doing
or the state of a particular disease or condition
that they're experiencing.
But you can think of proteins
as really like the workhorse of the cell.
Proteins go out and do virtually all functions
within the cell and as a result,
virtually all functions within organs and tissues
and the body as a whole.
They work together, they get modified, they, you know,
they have different forms and variations,
but the instructions for making that protein
are provided by gene.
When we talk about a genome, so the genome is the entirety
of an organism's genetic material
including genes and parts which are not genes.
So your genome is not just made up of genes,
it's not as though you stretch out all of your DNA
and you look at it and you say,
"Okay, well you know it's just one gene
right next to another, right next to another."
It is not like that at all.
In fact, it's quite the opposite.
The vast majority of your genome,
it's made up of other stretches of DNA,
which have very important functions.
And we'll talk about that more in the next module
when we talk about gene expression.
So when we're talking about genes, genomes, DNA,
are these terms interchangeable?
Well hopefully now you understand
that a gene and genome are not interchangeable,
that they actually mean quite different things.
That your genome includes
the entire set of all of your genes
plus extra sequences that are non-genes.
That one gene generally encodes the instructions
for making one protein.
And so where does DNA fit into all of this?
DNA or deoxyribonucleic acid
is the molecule that stores all the genetic information,
including your genes and non-genes.
So your genome is made up of DNA.
So DNA is the name of the molecule
and along your DNA strand
there will be certain sections of that DNA strand
which encode for a single protein,
and that section is called a gene.
If you take all of the DNA that you have
and say it's one of your cells,
that would be your entire genome
because it's going to be all of the information needed
to make you.
Let's talk some about the structure of DNA.
If we look at it from more of a simplified way
and taking out all of the chemical structure
that goes into it,
we can kind of break it down here, as you see here,
to a unit called a nucleotide.
DNA is made up of long strand of nucleotides,
so repeating strand of nucleotides.
So what is a nucleotide?
A nucleotide has several components to it.
It has a phosphate group shown here as the orange circle,
deoxyribose sugar, which is five-carbon ring sugar,
and it has a base,
and we'll talk more about what the base is,
but there really are four different kinds of bases
it could be,
that it could be that could fill this spot here.
Those would be adenine, thymine, guanine, and cytosine
or A, T, G, and C for short.
And it'll become very important soon
that you start calling them A, T's, G's, and C's
instead of adenine, thymine, guanine, and cytosine.
It just helps to speed things along,
especially if you're looking at a long stretch of DNA,
it becomes important to have a shorthand notation for that.
But in every nucleotide
this phosphate and deoxyribose sugar is present.
The only thing that changes is this base,
whether it's an A, a T, a G, or a C.
Each base is connected, so here this is the base.
Each base is connected to a five-carbon sugar here
called 2-deoxyribose, and a phosphate group.
This unit in its entirety, the phosphate group,
the deoxyribose sugar and the base is a nucleotide.
Now if we zoom out a little bit more
and we see how these nucleotides fit together.
Here this is showing a little bit more
of the chemical structure of it,
but this is still your phosphate group.
So here you have your phosphorus and your oxygen groups
coming off of that.
You don't need to know the details of this,
just know this is a phosphate group.
Phosphate group here again,
showing a little bit more of the structure.
But you have your phosphate group, your deoxyribose sugar,
and this is the base, in this case this is the A or adenine.
Well what you can see is happening here
is that it starts to form
a long chain of connected nucleotides.
And it basically,
every single time you have the phosphate group
attaching or bonding with the 2-deoxyribose sugar
of the previous nucleotide.
And here you can see this,
you can keep going and going and going forever
if you wanted to.
But basically you can start to understand
how you can begin to form really long chains of nucleotides
attached, again, at this
what's called the sugar phosphate backbone.
The reason why it's called the sugar phosphate backbone
is because you have this sugar group, the deoxyribose sugar,
and the phosphate group, right?
And the phosphate attaches to the sugar group
and so on and so on and so on,
so this is considered the backbone of it
and you can kind of see why,
it sort of looks like a backbone going all the way through.
This is the backbone,
these are what will be considered the bases again,
so adenine, guanine, thymine, adenine, cytosine here.
So it can form really any combination of bases in any order
in this, along one strand of nucleotides
or one strand of DNA.
So these nucleotides will form long chains
connected together on one strand by strong bonding
called phosphodiesterase bonding.
You don't really need to know that
but I would be remiss if I didn't at least mention it.
So you've heard the term phosphodiesterase bonding,
so just know that that's the bonding that occurs
between the phosphate group of one nucleotide
and the deoxyribose sugar group of another nucleotide,
which gives a very strong connection between these.
So these will remain in their chain
connected to one another.
Note that the base is not actually involved
in forming the backbone.
So the backbone here is separate from the base
and that's important,
and we'll talk about that in a little while
but it's important to know that
because the base is going to be involved
in some other activity.
If we zoom out even further here,
so what we were looking at there
was the structure of a single strand of DNA.
But DNA in its stable form is actually two strands
and these are called complementary strands
and they're bound together
by hydrogen bonding between bases on opposite strands.
And the two strands wind around each other
in a structure called a double helix.
So if you think of a spiral staircase
with sugar phosphate backbone as the sides of the staircase
and the bases bonded together as the steps,
you kind of get a sense
of what that structure actually looks like.
If we zoomed in here,
the blue line would look like that sugar phosphate backbone
that we were just looking at on the previous slide,
and there would be another one over here.
Each of these rungs of the staircase, so to speak,
would be the base.
So here this is green in this particular image,
so this would be thymine and adenine represented here,
this would be a guanine here and a cytosine here.
So they're actually bonding to one another
across the strands, so each of these is connected
to its sugar phosphate backbone on this one strand.
Same thing on this other strand,
they're kind of facing each other.
The two, the base sides of each of the two strands
are facing one another.
So you can kind of think of the two strands
as facing in towards one another
and they're bonding together
through the interactions between opposite bases.
So let me show you what I mean by that.
This is a process called base pairing.
Base pairing is the bonding of two base groups
to one another.
This does not involve the sugar phosphate backbone.
The sugar phosphate backbone
provides the structure for a single strand of DNA.
Base pairing occurs between two strands of DNA
when it's forming that double helix structure.
Now this is important.
Only adenine or A can bond with thymine or T.
So only A and T can bond together.
So A and T go together,
and only guanine or G combined with cytosine, C.
So G and C always go together,
they always bond to each other.
And let's look for a second,
let's look at why that actually is.
If we look at the chemical structure for these bases
instead of just writing them as A's, T's, C's, and G's,
which we will from here on out, I promise.
Just so that you've seen this
and you have an understanding of why that's the case.
If we look at the alignment
of these two molecules to one another,
in the case of guanine and cytosine,
both of them have three spaces on the cytosine side.
One, two, three, right?
And on the guanine side, one, two, three,
have three spaces for hydrogen bonding.
So they will bond to one another and only to one another.
On adenine and thymine
they each have two specific spots for hydrogen bonding
and so they will only bond to each other.
Adenine and thymine only bonds to each other.
Again, this is across
those two complementary strands of DNA.
And given that guanine and cytosine
have three hydrogen bonds between each other,
and adenine and thymine only have two,
you might be able to guess that guanine and cytosine bonding
is actually a bit stronger
than bonding between adenine and thymine.
Let's take a look at how this all comes together.
Once more, only adenine or A can bond with thymine or T,
and only guanine or G can bind with cytosine or C
between complementary strands.
Remember the sugar phosphate backbone shown here
is not at all involved in bonding between bases.
What we're talking about
when we're talking about base pairing
is between two complimentary strands.
So this strand here and this strand here
are bonding to one another,
and the way that they're attaching to each other
is through hydrogen bonds between the bases.
Just between the bases,
has nothing to do with the sugar phosphate backbone.
So what this means is that on a single strand of DNA,
you can really, you can have any sequence of bases.
And when I say sequence of bases,
I mean the order in which you see A's G's, C's, and T's,
that can occur in any conceivable order.
Once you have the sequence for one strand, however,
the sequence for the complementary strand is completely set.
Why do I say that?
Well, since we know only A combines to T
and only G combine to C,
if let's say this is our first strand here that we have,
that was created A, G, T, A, C, G.
That would mean the complimentary strand
absolutely must read as T because T binds to A,
C because C binds to G, A, T, G, C.
So this is determined, it has to read as such.
If this is the sequence of one of the strands,
then you know the sequence of the complementary strand.
Just as a quick review, this is a nucleotide here,
phosphate, sugar, base.
This is the sugar phosphate backbone of one strand.
This is the sugar phosphate backbone of another strand,
of the complementary strand.
These two strands together are complementary to one another
and together the two strands bonded together
makes up one DNA molecule.
There is bonding between the bases
separate from the sugar phosphate backbone.
These are through hydrogen bonds and again, T to A, G to C.
Always, always, always remember that,
C and G together, T and A together.
Let that soak in for a minute.
Feel good that you have this, you know this,
you are right on track, you are a chemistry rockstar.
Let's zoom out a little bit more here.
So now we understand,
you have this down pat what the structure of DNA.
This is an artist's rendition,
which I think is kind of a cool picture.
So this is showing sugar phosphate backbone right here,
there's another one, so these are two strands.
The rungs of the ladder here
are the bases binding to one another,
so there's a base on each of these strands
and they're binding to each other.
And then it gets curled up into that double helix structure
that I was talking about.
So this is basically,
if you stretch out DNA, it looks like this,
and then as it becomes more and more compacted,
you start to see these other structures form.
So there's 6 billion base pairs of DNA
within each cell's nucleus.
3 billion that you inherited from mom,
3 billion that you inherited from dad.
Stretched out the DNA in a single nucleus
is two meters long,
but an average nucleus is only six micrometers in diameter.
Okay? So that's a big difference.
Two meters. I'm not, I'm not, that's not a mistake.
It is actually two meters if you stretch it out.
So if you take, let's, if you stretch,
pull it all the way out and you stretch it
like into this kind of a structure
and you lay it end-to-end, it's going to be two meters long.
That's a really big
and it has to fit into a really, really tiny space,
six micrometers in diameter.
We're talking microscopic space,
from two meters down to microscopic space.
So how does the cell go about doing this?
Well, DNA becomes tightly compacted to fit into the nucleus
by wrapping around proteins called histones,
like string around a spool,
and supercoiled on itself to form a chromosome.
So histones, diagrammed here
as these kind of pinkish purpley colored round things.
DNA just starts to wrap itself around, wrap itself around,
come around, wraps itself around again and again and again,
just like wrapping string around a spool
which helps to keep it all together.
Because if you imagine,
let's say you have a small drawer for your sewing materials.
And I don't actually sew,
so I apologize for calling it sewing materials.
I don't know, there's probably a better term for it,
but I apologize, I don't know what it is.
But if in your sewing area, if you have a drawer let's say,
like you just have like a small drawer
for all of your sewing stuff, but you have, you know,
20 feet of string that you just bought,
the way that you fit it into that tiny drawer
is it's wrapped around a spool many, many, many times
and then stuck in the drawer.
Well it's not that different for DNA, if DNA was like string
and you just stretched it out like the 20 feet of string,
it would stretch out two meters
and it has to fit into a really small drawer
called the cell nucleus.
The way it does that
is it wraps itself around these histones.
And then beyond that
it starts to wrap what it's wrapped around the histones
around itself even more, and what's called supercoiling.
Supercoiling you can kind of think of,
not to use too many metaphors here,
but you can kind of think of it like a phone cord,
if you can remember what those look like.
For those who are on, you know,
who just use cell phones these days or cordless phones,
maybe you can think back
and remember what it was like to have a corded phone.
Remember that they have that sort of natural coil to them.
But inevitably,
what at least has always happened in my experience
is that they end up getting coiled around each other
and around and around and around.
And so you have this big like coil blob of phone cable
and that's supercoiling.
So if you stretch it out,
you still have more coiling that's natural to it
but it starts to kind of compact in into a smaller space
by wrapping around itself more and more.
This is kind of similar to what happens with DNA.
So it's wrapped,
it has its natural kind of helical structure
and then starts to wrap around these histones,
and then the histones start to wrap around each other
and it compacts and compacts and compacts
until you get to something that is of far more condensed
called a chromosome.
So if you take a chromosome
and you pull it and you stretch it out,
you would see it contains one long molecule of DNA
that's actually wrapped around lots of these histones
and then packed and packed and packed around itself
until you get this kind of puffy looking structure
that is far shorter than the full length of DNA.
If we go back to our schematic of a cell,
remember all of this is taking place,
all of this is present in the nucleus.
So this is that little,
that lovely hairball I mentioned before.
If you look at it more closely, what you start to see
is exactly what we were just talking about.
So if we start out from the big structure, these would be,
if you look at each one of these strands that you see here,
this would, each of these would be that chromosome.
So it is, even though it all looks kind of messy in here,
these are highly compacted DNA strands.
So if you zoom in a little bit more on that,
and let's take a peek at that.
So if we look at each one of these as a chromosome,
and we'll talk more about the structure of chromosomes
in some subsequent modules,
but if we zoom in on the chromosome and we start to pull,
like pulling a thread out of a sweater,
you start to pull and pull and pull.
What you start to see is that within each chromosome
is a single molecule of DNA.
So that would mean a single DNA double helix
that's just been wound and wound and wound and wound
and really kind of smooshed together, compacted in
to form this puffy looking structure of a chromosome.
But if you stretch that out like this and you zoom in a bit,
you start to see that, yep,
that's a single strand of DNA wrapped around these histones,
which kind of act like spools
with the DNA being more like the thread.
And if you zoom in more and more and more on each of these,
if you pull it apart from the histones
and you stretch it out some more,
you see that double helix structure.
And if we zoom in more, let's say we take this stretch here
and we look at what the base sequence is against sequence,
is the order of the bases
that are found in a particular strand of DNA.
Given that we always know what the complementary strand is
based upon the sequence of one of the strands,
we only ever really look
at the sequence of one of the strands of DNA
because the other one is going to be the
basically mirror image of that sequence.
So if we zoom in here and, you know,
we know that it has a sugar phosphate backbone,
which is identical throughout the whole strand of DNA.
The part of it that's different is the base or the bases.
And so we look at this, let's say we zoomed in here,
we see dah, dah, dah, dah, these are the different bases
that are in that particular order.
It's really important that they're in this order
and we'll talk about that more later.
Let's say this segment here, we would consider to be a gene.
So this segment and, you know, there's a,
you know, a gene would be significantly longer than.
An average gene would be significantly longer than this
but this is just to give you a demonstration
of what we're talking about.
So a gene exists along a single molecule of DNA,
so which is to say it is also on a chromosome.
This chromosome is made up of a single molecule of DNA
plus wrapped around histone proteins.
And what you would see along any chromosome
is you're going to have multiple,
hundreds or even thousands of genes
spaced out in different areas
and stretches along this chromosome.
But you'll also have some regions that are not genes
and that's what I was talking about before
when I was saying your genome includes
regions that are genes and regions that are not.
Because if I stretch out this DNA,
this part's gonna be a gene
and let's say the next section here
doesn't actually give instructions for a specific protein
so it would not be considered a gene.
But then let's say down here somewhere,
oh, there's another gene that pops up
maybe down here somewhere, there's another one that pops up,
maybe there's a long stretch
and then you get some more down in this area, for example.
So chromosomes contain many genes,
these genes are always in the same position
on its particular chromosome.
And that becomes important
when we start thinking about chromosomal abnormalities
and conditions and syndromes associated with those,
which we will get into in detail in another module.
Let's take a quick peek at all of the chromosomes together.
So DNA is divided into 24 different chromosomes.
That does not mean we all have 24 different chromosomes.
That means there are 24 different chromosomes
in the human genome.
And by this I mean there are 22 what are called autosomes,
so these are chromosomes 1 through 22,
which you can see here on a karyotype,
which you've probably seen something like this before.
Karyotypes are microscopic imaging
of the full set of chromosomes that an individual has.
So we have chromosomes that are just labeled 1 through 22
and those, that's their name, not very,
not terribly creative labeling,
but that's what they're called, chromosomes 1 through 22.
And you can see chromosomes with lower numbers
are actually longer, bigger chromosomes,
whereas the higher the number,
you get shorter and shorter chromosomes.
In this case, this is a male
because this individual has one X chromosome
and one Y chromosome.
Coming back here to our different types of chromosomes,
we have 22 autosomes,
chromosomes 1 through 22 are called autosomes
because they're not involved in sex determination.
And then there are two different kinds of sex chromosomes,
an X chromosome and a Y chromosome.
X and Y.
So it's really,
you'll hear it said that we have 23 chromosomes,
which we do in a way in that we have 1 through 22
and then we have sex chromosomes,
which could be considered 23 I guess.
But we really, really have 24 different kinds of chromosomes
because you can have an X and a Y
and then 1 through 22 of the autosomes.
Each chromosome has one double stranded DNA molecule
wrapped around histones and compacted
as we looked at before.
All cells except egg and sperm
have two copies of each autosome
and either two X chromosomes for female
or one X and one Y chromosome for a total of 46 chromosomes.
Okay, so I'm throwing a lot of numbers at you.
24, 23, 46. What am I talking about?
Let's make sure we boil this down.
24 different kinds of chromosomes are present,
1 through 22, as you can see here
and then X and Y are two different kinds of chromosomes.
But you have 46 in the end. Where do you get 46 from?
Well, as you can see here in this karyotype
there is one, two.
You have a pair of chromosomes
for each one of these designated chromosomes.
So for example, chromosome 8, you have two.
Why do you have two? One came from mom, one came from dad.
So if we just do some simple multiplication, we get to 46
because two times 22,
which would be the number of autosomes we have, equals 44.
And then you have one,
either if you're a male you have one X and one Y,
which makes 45, 46 chromosomes total.
Or if you're a female, you would have two X chromosomes
so then you would also be at 44 autosomes
plus 45, one X chromosome, 46, second X chromosome.
So make sure you think about that for a minute
because it's actually kind of important
to understand the number of chromosomes.
And this will be a bigger part of our next module
so if you're not totally getting it now,
don't worry about it.
It'll come back up quite a bit in the next module.
Okay, well now I want to just give you
a little bit of strange but true information about genetics.
If all of the DNA in your 50 trillion cells
was placed end-to-end
and stretched out from its condensed form
in a straight line,
it would reach from the Earth to the Sun over 30 times.
Yes, that's correct.
If all of the DNA in your body
was stretched out to its longest possible length
and placed end-to-end in a straight line,
it'd be like taking all the string
that you have in those sewing drawers
and you place them end-to-end-to-end-to-end-to-end,
and you stretch it all the way out,
it would be long enough, because you have 50 trillion cells
and each one of those cells
has two meters worth of DNA in it.
If you put it end-to-end and you stretch it out,
it would go to from here to the Sun and back,
which is a really long way, 92 million miles,
it would go over 30 times.
That's a lot. That's a lot, right?
This little kid's like, "What?" Exactly.
If you were to start reciting the order
of the A's, T's, C's, and G's in your DNA tomorrow morning
at a rate of 100 each minute, which is pretty fast,
57 years would pass before you reached the end.
This provided that you did not stop to eat, drink, sleep,
use the bathroom, et cetera.
Remember that from each of your parents,
you received 3 billion with a B,
3 billion bases worth of DNA, so that's a lot.
You could fit 1,000 nuclei in a cell
across the period at the end of this sentence here.
That's how small a cell nucleus is.
And even smaller than that,
you could fit 1 million threads of DNA
across the period at the end of this sentence.
And by that I mean this is the width of DNA.
Not the length of DNA, but the width of DNA,
you could fit it,
line it up sort of side-by-side-by-side-by-side
across the period at the end of the sentence
and you could fit a million of them.
So while they're really, really long,
they're also really super, super thin.
All right,
well hopefully your mind was blown a little bit there,
but you can start to understand
how this is all fitting together and working.
Let's look at a summary of some of what we've learned here.
Deoxyribonucleic acid or DNA
is the molecule used to store genetic information
and a single strand of it
is made up of nucleotides joined together in a chain
through their sugar phosphate backbone.
DNA is made up of two complementary strands
which bind together through hydrogen bonds
between adenine and thymine, so A and T go together,
and guanine and cytosine, G and C go together.
DNA has a natural double helical shape
and further compacts around histones to form chromosomes.
So a chromosome is made up of a long stretch of DNA
that's wrapped and wound around histones
and compacted down together.
And within that there are segments called genes.
There are 24 different chromosomes, 22 autosomes,
and two sex chromosomes and each cell has 46 chromosomes.
Again, two times the 22 autosomes, so 44 autosomes,
and either two X chromosomes if you're female
or one X and one Y chromosome.
So 44 plus two equals 46.
All right, so what's in the next module? You ready to go?
Ready to take on the next module, which is really,
so we learned a lot about the structure of DNA,
but what does it do exactly?
Why do we care about DNA?
So we'll talk about that next in the next lecture.
Thank you so much for your patience
and congratulations making it through this lecture.
I look forward to speaking with you in the next.