[Instructor] Hello and welcome to the third lecture
in module three on mitosis and meiosis.
So this one will probably be a bit longer
than the DNA replication lecture,
but not quite as long as (laughing) the gene expression
and regulation lecture.
So somewhere in between,
but maybe get yourself a nice cup of coffee, sit down,
and, you know, give it a listen.
First I wanna start out with a few important definitions
to make sure we're all on the same page.
When we're talking about somatic cells,
these are all cells in the body that are not egg
or sperm cells.
So literally any other cell in the body,
the vast, vast majority of cells in the body,
are somatic cells.
Gametes, these are egg and sperm cells.
So these are in the reproductive organs only.
So that's the only place that they're located.
And the reason why we're separating these
is because somatic cells undergo mitosis,
while gametes undergo meiosis.
And these are two very different, but related, processes.
And it will be important to understand those differences.
Diploid means containing two complete sets of chromosomes,
one from each parent.
This would be in cells that have homologous chromosomes.
We would say, you know, again,
so that would be two sets of each of the 23 chromosomes.
So they have 46 total.
That would be a diploid cell.
Haploid, on the other hand,
these would be cells having a single set
of unpaired chromosomes.
Gametes are haploid.
These are the only cells really in the body
that are haploid.
And that means they have 23 chromosomes total.
All other cells in the body are diploid.
And that means they have 46 chromosomes total,
two of each of the 23 chromosomes that they have,
two complete sets of each of the chromosomes,
one that came from each parent.
Sister chromatids, if you remember from the previous lecture
on DNA replication, these are two identical copies
of the same chromosome formed by DNA replication.
Sister chromatids are different from homologous chromosomes
because homologous chromosomes would be a pair
of chromosomes, each inherited from one parent.
Remember, sister chromatids are identical to one another,
really just completely identical to one another.
If you look at the sequences,
they're going to match up really 100%.
Homologous chromosomes, on the other hand,
are going to be very, very similar to one another,
but there will be some differences
between one and the other,
because one came from one parent
and one come from another parent.
And each of these have their own slight differences
in the sequence.
All right, let's jump in.
Cell division.
Cells need to divide and proliferate
so we can develop from a single fertilized egg
into a fully formed adult,
so we can heal from injuries,
and also so we can replace cells that have a short lifespan.
So cell division is a really critical process.
All cells in the body that are not egg or sperm cells
are called somatic cells, if you remember
from the previous page.
Egg and sperm cells are called gametes.
Remember from the previous slide,
I said that somatic cells are diploid.
What does diploid mean?
Diploid means they have homologous chromosomes,
which means they have 46 chromosomes,
or two pairs of each of their 23 chromosomes.
While gametes are haploid,
which means they only have a single copy
of each of their chromosomes, or 23 chromosomes in total.
When somatic cells divide to form cells
with both copies of each chromosome, this is called mitosis.
So somatic cells undergo mitosis for cell division.
And that results in two cells.
When gametes divide to form cells with only one copy
of each chromosome, this is called meiosis.
So meiosis only occurs in gametes,
never occurs in somatic cells.
Meiosis occurs in gametes.
And the end product of meiosis is four haploid gametes,
haploid being each, meaning each of those cells
has 23 chromosomes.
Let's jump into mitosis to start.
Cells progress through highly regulated phases of growth
in a continual process called the cell cycle.
There are four regular phases:
G1, S, G2, and M.
There is another phase called G0,
but this phase is basically where a cell can exit
the cell cycle and go into growth arrest or quiescence.
Let's start with G1.
In G1, this is where metabolic activity occurs.
So this is where you're having some protein synthesis,
and the cell is preparing to replicate its DNA.
This is where the cell is growing,
and this is a highly variable stage.
So it can last minutes to years,
depending upon the cell type.
In the next phase that follows, this is S phase,
S standing for synthesis, where DNA is replicated.
This process takes about six hours,
and this was the process we talked about
in the previous lecture.
The next phase is G2, or gap two,
where a cell prepares for mitosis
with lots of protein synthesis.
So it's getting ready to enter its cell division phase.
So it needs to prepare certain proteins,
and it needs to perform certain functions
to be ready for this process.
The actual cell division process is called mitosis,
or M phase, where duplicated chromosomes,
chromosomes that were duplicated in S phase,
duplicated chromosomes, again, what are these called?
These are called sister chromatids.
Are separated, two new daughter cells form
from the original parental cell,
each with 46 chromosomes.
This whole process takes about one to two hours.
Again, as I mentioned, the G0, or gap zero, phase
is the phase where a cell will basically exit the cell cycle
and enter quiescence.
It does not happen with every cell cycle.
It doesn't happen with every cell.
It's just when a cell has essentially reached a point
at which it's stopped dividing.
This would apply to a cell like a neuron in the brain,
where once it is formed,
it's not going to continue to divide.
It's basically done until the cell dies.
And so it enters G0 phase and exits the cell cycle.
Let's drill down more on this M phase, or mitosis phase.
Mitosis itself is composed of five distinct stages
to accurately separate duplicated chromosomes
to newly forming daughter cells.
So I'm throwing a lot of information at you here.
And believe me, it will make sense.
I just want to cover each of these phases first,
and then we'll look at it in a bit more detail.
So I just wanna give you kinda of a high-level perspective
of what's happening, and then we'll go into some more detail
for each one.
So we start with prophase, where essentially,
chromosomes are condensing down,
and you're getting attachment of these spindle
to the centers of each chromosome,
the center being the centromere.
Metaphase is where chromosomes line up in the middle
of the cell.
In anaphase, the sister chromatids,
each side of the X shape of a chromosome,
begins to separate with one copy going to each side.
In telophase, sister chromatids complete moving
to the opposite sides and the nuclear members begins
to form around each one.
In cytokinesis, the cytoplasm divides,
cell membrane pinches off between the two cells,
and you have two cells with 46 chromosomes in each.
In preparation for mitosis,
sister chromatids are held together at the center
of the chromosome, called the centromere.
The chromosome only looks like an X
when it's been duplicated but has not yet divided.
So you probably have seen chromosomes depicted
in this X type of shape.
And they do actually look like that,
but they only look like that in a specific time
in the cell cycle.
So they actually only look like that
when they're undergoing or very much preparing for mitosis.
The reason being, the X shape here are actually
sister chromatids of one another.
And they're held together at a near center point
of the chromosome called the centromere.
So if you look at the X type of drawing for a chromosome,
you have one sister chromatid on one side
and another identical sister chromatid on the other side.
And this occurs after the DNA's been replicated.
And what phase is that?
That was S phase, right, S phase.
After S phase and the cell completes G2 phase,
it enters M phase in mitosis.
And this is the point at which the two sister chromatids
are separated from one another,
each one going to a new cell.
And in the end, at the end of mitosis,
at the end of M phase,
the result is that you have one chromatid
per each chromosome for each of the 46 chromosomes.
So remember, these are duplicated identical copies
and not the maternal and paternal copies
which still exist and are separate from one another.
So we're not talking about homologous chromosomes here.
This is for each of the 46 chromosomes
goes through this particular procedure.
Before replication and after cell division,
each chromosome is made up of one chromatid.
I know, it is confusing, believe me.
I completely, completely understand
that you're probably scratching your head and thinking,
"What, what's going on here?"
So I'm going to try to reinforce this a couple of times
throughout, but just want to make sure it's clear.
Sister chromatids are two identical copies
of the same chromosome.
Homologous chromosomes are pairs of chromosomes
that are similar, one which came from your mother
and one which came from your father.
This is kind of showing it here.
So if we're looking at, remember,
this is the centromere where the two sister chromatids
are being held together for mitosis.
This is one chromatid.
This is its sister chromatid.
And these two would be considered homologous chromosomes.
During S phase, each one of these was duplicated,
and you have sister chromatids now that are identical
to one another and will be separated
during the process of mitosis.
Let's take a quick peek at what this looks like
on a karyotype during mitosis.
It looks a bit different.
So you have two.
You can start to see a little bit the sister chromatids.
These are the homologous chromosomes,
as I mentioned in the previous lecture as well.
These are homologous chromosomes.
And you have a pair of sister chromatids attached
at the centromere, the center of the chromosome,
for each one of those chromosomes.
The karyotype after mitosis,
you've separated each of those sister chromatids
from one another.
And so you have a single chromatid for each chromosome,
and you have pairs.
So now we're looking at homologous chromosomes.
Homologous chromosomes are never, never,
never held together at a centromere.
Only identical sister chromatids are actually held together.
All right, let's break down the different phases of mitosis.
It's not really critical that you memorize
each of these phases and know exactly what happens in each.
I want you to conceptually,
to understand this from a conceptual perspective,
what is actually happening.
And the easiest way, I think, to do that
is to look at it by stage by stage,
what exactly is happening in mitosis,
which is why we're going through each
of these stages individually.
So prophase, the chromosomes condense,
nuclear membrane breaks down,
and spindle fibers form and attach to the centromeres
on each chromosome.
So what are spindle fibers?
Well, those are basically like these long,
you can think of them as long tethers
that will be basically found in the end
on opposite ends of the cell.
So what they're gonna do is going to act sort of
like a pulley, and they're going to pull
these spindle fibers, which act as the tether,
which will be attached at the centromere, at the centromere
of each of these chromosomes
and will pull, actually physically pull one
of the two sister chromatids in each
of the opposite directions.
So in prophase, we're just starting this process.
Basically, the chromosomes condense down,
and you have the formation,
starting to form these spindles.
And the nucleus actually breaks down.
During mitosis, this is the only time
when DNA is actually not encased in the nuclear membrane
or in the nucleus itself,
because the nucleus breaks down in order to allow the DNA
to move to opposite sides of the cell
and form into two new cells.
So that's prophase.
In metaphase, the chromosomes line up in the middle
of the cell, so boom, boom, boom, boom.
In this case, we're actually just depicting four chromosomes
here lining up, each with their sister chromatids, right?
But in a human cell, you would have 46 of these lining up
across the center of the cell.
And the spindle would attach at each one
of these centromeres.
So you can imagine it's actually attaching
to each of the two sister chromatids.
So this one's attaching to the sister chromatid
on one side, and this is attaching
to the other sister chromatid.
During anaphase, this is when
the chromosomes begin to separate.
So these spindles start to shorten,
and they actually yank the sister chromatids
in opposite directions, as you can see here.
It's kind of being pulled into,
this side's being pulled to the left.
This side, these sister chromatids are being pulled
to the right.
During telophase, single chromatids,
so these are the chromosomes, complete moving
to the opposite sides,
and the nuclear membrane begins to form around each one.
And cytokinesis finishes the process,
and that basically means that the cytoplasmic membrane
pinches off between the two.
And you actually have two fully formed cells now.
And the chromosomes can decondense and can start
to do their thing, as we talked about
in the gene expression and regulation lecture.
You can actually start
to now have transcription occurring again.
You can have the chromosomes starting to go back
into more of a euchromatin state with the histones starting
to loosen up a bit.
And the cell can start back to its normal activity.
So by the end of mitosis,
a somatic cell has become two identical daughter cells.
Each cell contains 46 chromosomes,
23 homologous chromosome pairs, and remains diploid.
Cell enters interphase by going into G1 phase
and performs its expected function,
or the cell enters G0 if no further division is required,
and the chromosomes decondense
to allow transcription to restart.
Okay, let's switch gears here and we'll talk about meiosis.
So recall, mitosis occurs in somatic cells,
and somatic cells are virtually all cells in the body
with the exception of egg and sperm cells.
What happens in egg and sperm cells is a bit different.
They undergo a process called meiosis.
So meiosis is the process
by which these egg and sperm cells are formed.
Normal gametes have only one copy of each chromosome,
I.e. 23 chromosomes, and this is called being haploid.
One diploid pre-gamete cell, which has 46 chromosomes,
each have been duplicated, undergoes meiosis
to produce four haploid gamete daughter cells.
It is essential for gametes to have only 23 chromosomes
so when one egg and one sperm fuse,
the fertilized cell will have the right number
of total chromosomes.
This is really, really important.
Right, because otherwise, with each time we reproduced,
each time there's a new generation of humans,
we would have twice as many chromosomes.
We would keep doubling our number of chromosomes,
and it would get out of hand and we wouldn't really survive.
So this is an important process.
There are two rounds of meiosis: meiosis I and meiosis II.
And these always occur in succession,
and they always occur together.
So you always have meiosis I
and it's always followed by meiosis II.
Meiosis I separates homologous chromosomes,
while meiosis II separates sister chromatids.
So meiosis II is a bit more like mitosis
in that it's separating sister chromatids,
but it follows the process of meiosis I,
which actually separates homologous chromosomes.
Let's take a peek at what this actually looks like.
So starting again with DNA replication,
we end up with sister chromatids.
And these cells go into meiosis I.
Meiosis I here.
They each have the same basic phases as you had in mitosis.
They're just denoted as I or II,
depending upon if it's occurring in meiosis I or meiosis II.
So prophase I, again, you don't need
to memorize these phases.
Just kind of understand the concept
of what's happening here.
In prophase I, instead of actually the alignment of,
instead of all of the chromosomes lining up
down the center, all 46 aligning down the center
and separating the sister chromatids,
instead, what happens is the homologous chromosomes line up
next to each other.
So you'll have 23 pairs lined up next to each other.
And then what happens is that each one of these two
gets pulled, each one of these two homologous chromosomes
gets pulled in a different direction
to form two different cells.
And each of these cells now has 23 chromosomes,
each having been duplicated.
So it resolves the duplicated chromosomes
by undergoing another round of meiosis, or meiosis II,
which again is very, very similar to mitosis
in that what happens now is the separation
of sister chromatids.
The difference here being you're starting with,
instead of 46 chromosomes, you're starting with 23.
Each one of these 23 chromosomes aligns in the center again,
just like in mitosis, and gets pulled,
the sister chromatids get separated into opposite cells.
So the end result would be four total cells,
which are each haploid.
So that means they each have 23 chromosomes.
And what's happening in crossing over?
What is crossing over?
Well, crossing over's actually a very important process.
And we'll talk about it in more detail in the next module
when we start talking about what can go wrong in meiosis
and some of the chromosomal anomalies that can result.
But crossing over is a normal process
that occurs in meiosis I.
It only occurs in meiosis I, ever occurs in meiosis II.
Why is that?
Because crossing over is actually the exchange
of genetic material between the two homologous chromosomes.
So if you look at the diagram on the right,
this is basically taking your paternal
and your maternal chromosomes,
which you got from your mother,
which you got from your father,
they start shuffling DNA between each of these two.
In normal crossing over,
it will move the same region of one chromosome over
from, say, the maternal chromosome to the paternal
and vice versa.
So the paternal piece gets stuck on the maternal piece.
And in the end, you end up with some combination
of both maternal and paternal for each of these.
And why do we actually do that?
Like why even bother with this weird process?
Well, it gives us a lot of genetic variation,
which is really critical for survival of our species.
So now, instead of passing on to your offspring
either the chromosome you inherited
from your mother or your father,
you're passing on some combination of both of those
for each of the chromosomes that you contribute
to your offspring.
This is a figure from the book,
and I wanted to comment on this.
There is a part of this figure to the left
that actually reads no crossing over.
That doesn't ever happen.
There's always crossing over.
So just kind of ignore that.
I don't know why they included that in there,
but it could be confusing.
So just know, there will always be crossing over
in meiosis I.
And this is depicting it a bit here,
kind of similar to that last diagram.
If the paternal chromosome is shown with the blue
and the maternal with the pinkish color,
then in the end, you actually can get some switching
of, say, the end parts of this particular chromosome.
The paternal gets swapped with the maternal,
and you end up with some kinda combination of the two.
In meiosis I, the homologous chromosomes separate
into the two different cells.
And then each of these two cells subsequently divides
into two cells, each of which undergoing meiosis II,
which is very similar to mitosis
in that it's really a separation
of duplicated identical sister chromatids.
The end result is from one single cell,
which was diploid, you have four haploid gametes
after the process of meiosis.
So let's summarize here.
Mitosis is the process of cell division in somatic cells.
The end result it two diploid daughter cells.
Meiosis is the process of creating gametes.
The end result is four haploid gametes.
Meiosis has two rounds that always occur in succession:
meiosis I, in which homologous chromosomes are separated,
and meiosis II, in which sister chromatids are separated.
When homologous chromosomes,
I.e. maternal and paternal, align in meiosis I,
they swap pieces to create new combinations
of maternal and paternal sequences.
So what's next?
Now that you've made it through module three,
well, guess what we're gonna talk about next?
We're gonna actually start talking about some disease.
I'm sure you're probably thinking,
"Finally. (laughing)
Finally we're going to talk about something
with, you know, some clinical application directly to it."
But hopefully you can appreciate the rationale
behind why I'm presenting the material in this way.
What I think is important is for you to understand
how the processes normally occur,
so the non-disease processes,
before we start talking about when these processes go wrong
and the resulting disease.
So that way, you can understand how things
are supposed to function
and how things are supposed to work.
And then if something goes wrong in any of those processes,
what are the implications for human health?
And so we'll really go into that throughout the rest
of the course.
So thank you for hanging in there with me through this.
I look forward to any questions and comments
and all of your great discussion that you shared
on the discussion board so far.
So in the next module,
we're going to talk about aneuploidy,
or inheritance of the incorrect number of chromosomes,
chromosomal abnormalities, so we're talking more
sort of the larger-scale abnormalities of chromosomes,
and then also mosaicism.
So those'll be some of the topics in our next module.
And with that, I'd like to say thank you so much,
and I hope you take a moment and just feel appreciative
for yourself, for all of the time and energy you've put in
to learning everything you've learned so far.
Just take a moment of gratitude for yourself
that you, as busy as you are,
have taken the time to prioritize learning this material.
Think about how much you've learned just so far
in this first couple of weeks, how far you've come,
and just know we're going to take this really up
to the next level and really start to find some
of those clinical applications coming up
in the next few weeks.
So with that, I will say goodbye,
and I will speak with you again in the next module.
Thanks very much.