Hello everyone, this is Kshitiza from Department of Biochemistry, Indian Institute of Science.
I will be talking to you about an extremely important and very interesting form of
cell division called meiosis. You would recall from your school biology textbooks
that cell division is a critical process in growth, development, repair and reproduction.
You have been taught at great length about another form of cell division, called mitosis,
in Professor Shikha's previous lectures. So, I would start by asking you why do you think
an entirely different form of cell division called meiosis occurs, when mitosis is already there?
Now imagine, when you were a zygote, you received half the number of chromosomes from the egg cell,
which came from your mother and half the number of chromosomes from the sperm cell,
which came from your father. Now hypothetically, if the egg cell had diploid number of chromosomes
that is 2n and the sperm cell also contained diploid number of chromosomes that is 2n,
the fusion of the egg cell and the sperm cell would form a tetraploid zygote, which would be the
abnormal number of chromosomes and is not found in human baby. Therefore, an entirely different form
of cell division called meiosis evolved, which made sure that the number of chromosomes in the
egg cell and the number of chromosome in the sperm cell is half the number of chromosomes present
in the zygote, which is diploid that is 2n such that the ploidy is maintained in the offspring.
Now as you can see, here the difference between mitosis and meiosis occurs in
three important aspects. Starting from a diploid cell which has a ploidy of 2n in both the cases,
DNA duplication is a common step, and after DNA replication the number of chromosomes
stays the same in both mitosis and meiosis. However, the content of the DNA is now doubled.
I have shown here 4 chromosomes per cell; four chromosomes shown in different colours.
And the DNA is duplicated, you see that the chromosomes are shown in form of two chromatids
which are called sister chromatids, which are joined together at a point called centromere.
When mitosis and meiosis are compared, after DNA replication in the mitosis process
there is only one round of chromosome segregation. However,
in meiosis one round of DNA replication is followed by two rounds of chromosome segregation,
which results in formation of four daughter cells as you see here with a ploidy which has
half the number of chromosomes as compared to the parent cell which had 2n number of chromosomes.
This is in contrast to mitosis where only two daughter cells are formed which have a ploidy,
which is exactly the same as the parent cell. The second very important aspect is,
during the meiosis process the two homologous chromosomes that is the version of chromosome
one received from the mother and one received from the father pair together, and during the
first meiotic division, which is called meiosis one these homologous chromosomes segregate
and during the second meiosis division which is called meiosis 2, the sister chromatids segregate.
I have shown here two pairs of homologous chromosomes in purple and in green is one
pair of homologous chromosomes in black and in pink is another pair of homologous chromosomes.
After meiosis 1, one of the daughter cells contains one pair of homologous chromosomes,
which has been segregated and another daughter cell contains another pair of
homologous chromosome, which has been segregated and this is called a reductional division.
Meiosis 2 is almost similar to mitosis in a way, that the ploidy does not change,
from these two daughter cells to the four daughter cells that are formed here.
The third very important aspect of meiosis, which is different from mitosis is, when the homologous
chromosomes pair, there is an exchange of genetic material between the two homologous chromosomes.
This process is called crossing over and it occurs via a DNA recombination process.
Let us dive deeper into the different stages of meiosis. Just like in mitosis there are different
stages of the meiotic process. Starting from a diploid cell in the G1 phase, as you see here,
in S phase the DNA is duplicated, which is followed by a G2 phase
where the homologous chromosomes start to align with each other.
After G2 phase, meiosis 1, which is also called a reductional division starts prophase 1 of
this meiosis is different from mitosis in a way that in meiosis the prophase one is quite long
because the homologous chromosomes need to pair together and DNA recombination has to occur.
In prophase one the homologous chromosomes pair and crossing over happens.
It is followed by metaphase one where the paired homologous chromosomes align at the equator,
which is followed by anaphase one where the homologous chromosomes segregate
and each of the homolog is segregated to different poles, opposite poles.
Anaphase 1 is followed by telophase 1 and cytokinesis 1 where the cytoplasm divides.
Now note, that since the green chromosome and the purple chromosomes are homologues of each other,
they will never be segregated towards the same pole. Similarly for the black chromosome
and the pink chromosome, they will not be segregated towards the same pole. However,
it is entirely possible that the green chromosome here is segregated with a pink chromosome here,
which will lead to the purple chromosome here segregating with the black chromosome here.
Therefore, this is one of the combinations that I have shown here, the other combination
is equally possible. This is one level where merely on the basis of chromosome segregation
different types of gametes can be formed and genetic variation is maintained.
Now since I have shown here only two pairs of homologs.
You should remember that in human cells there are 23 pairs of homologous chromosomes,
which would lead to an enormous number of possible combinations and therefore an
enormous amount of genetic diversity merely on the basis of chromosome segregation.
Now meiosis 1 is followed by meiosis 2. Meiosis 2 is also called equational division because it
is very similar to mitosis. Now that the chromosome number in the daughter cells
has already been halved during meiosis 1, during meiosis 2 four daughter cells are
formed from these two daughter cells and the chromosome number now stays the same.
During prophase 2 of meiosis 2, new spindle forms around chromosomes as you see here
and in metaphase 2 these chromosomes align at the equator. As we saw in anaphase 1 of
meiosis 1 homologous chromosomes segregate towards opposite poles. During meiosis 2 and anaphase 2 in
meiosis 2, sister chromatids segregate towards opposite poles. So, the connection between the
sister chromatids that was characterized by the presence of centromere here, this connection is
lost, and the sister chromatids are pulled towards opposite poles, as you can see here.
Now as we saw in meiosis one there were different combinations possible for the
segregation of homologous chromosomes, and that led to formation of different types of gametes.
Similarly in meiosis 2 when the telophase and cytokinesis 2 occur, the cytoplasm divides
and 4 haploid cells are formed. Different combinations of segregation is possible and
this will lead to different combinations formed in these haploid cells. This is another level of
genetic variation and this is one very important reason why meiosis evolved in the first place.
The meiotic prophase is a beautiful process in itself, and it is so intricate that it has
been subdivided into five different stages as you see here. The first stage is the leptotene stage.
Now after the DNA has been duplicated in the S phase, the DNA still exists in form
of thread like structures called chromatin. During leptotene stage the chromatin condensation occurs
and now chromosomes are formed. I have shown here one pair of
homologous chromosomes where the first is purple in colour and the second is green in colour;
as you see here chromatids from one of these homologues are called sister chromatids,
while chromatids from two different homologues in the pair are called non-sister chromatids.
The leptotene stage is followed by zygotene stage. In the zygotene stage the nuclear membrane starts
disintegrating; also note that the homologous chromosomes have started to align with each
other. Now this alignment of the homologous chromosomes leads to formation of a structure,
which is called a bivalent. The pairing of the homologous chromosomes or the coming
together of these homologues is facilitated by formation of a proteinaceous complex,
which is called a synaptonemal complex. The synaptonemal complex is proteinaceous in nature
and is composed of proteins, which are responsible for not only keeping these
homologs together but also regulating the DNA recombination between these homologues.
The zygotene stage where the formation of the synaptonemal complex is still immature,
is followed by pachytene stage where the synaptonemal complex formation is matured.
These homologs are glued together such that the distance between them is now almost 100
nanometers. This is an ideal situation for DNA recombination; note that DNA recombination
should only occur between non-sister chromatids and not between sister chromatids. This process
is also highly regulated and it involves many proteins of the synaptonemal complex itself.
The points of exchange of genetic material between the homologs
is marked by these points of association and these are called chiasma.
Now I have shown one homolog pair here and one point of crossing over, one chiasma,
however there can be multiple points of crossovers between one pair of homologs.
However, the number of crossovers between one pair of homologs is highly regulated.
So, the pachytene stage is marked by the formation of the synaptonemal complex
and crossing over between homologs. Pachytene stage is followed by diplotene stage;
now after that exchange of genetic material is over between the two homologues, it is essential
that the homologs need to be separated from each other and this glue needs to be removed.
In order for this association between the homologs to be removed, there is disassembly of
synaptonemal complex. So, the proteins that were initially recruited between these homologues are
now de-recruited from these homologues, in order for the homologs to separate during anaphase 1.
During diplotene stage, the crossing over is completed and the synaptonemal complex disassembly
begins. However, the homologs stay connected only at the points of crossing over, which are the
chiasma. The separation is completed during the diakinesis stage where the homologues completely
separate from each other and the nuclear membrane is completely disassociated. Note that we started
with a parental combination of genetic material here in purple and green and we ended up with a
slightly or you know majorly different combination of genetic material in the daughter cell here,
and this is an extremely stunning process. We will see how DNA recombination occurs
but before that we would see how the synaptonemal complex formation happens.
What you see here is a schematic of the synaptonemal complex
as observed in budding yeast by scientists during meiosis.
We have already discussed that in order for the two homologous chromosomes
to stay together, a proteinaceous structure called the synaptonemal complex assembles between them
and keeps them in a close proximity such that the distance between them is almost 100 nanometers.
Now let us see what are the protein components that make up the synaptonemal complex in budding
yeast? What you see here are chromatin loops from one homolog in the pair and these are the
chromatin loops from another homolog in the pair. The first type of elements are called
lateral elements; the lateral elements are majorly composed of two proteins called Hop1 and Red 1.
By research, it has been shown that Hop1 protein can actively bring together two different DNA
molecules and keep them in close proximity while Red 1 is also essential to maintain this glue and
both of these proteins are absolutely essential in regulating recombination in such a way that they
bias the DNA recombination between inter homolog rather than between inter-sister chromatids.
The second type of element called the central element is composed of two different proteins
called Ecm1 and Gmc2 and the final structure is kept together by a third type of filament
called transverse filament, which is composed of a protein called Zip1 budding yeast. Now it is very
important to note that the entire assembly of the synaptonemal complex is evolutionarily conserved.
By that I mean that the proteins that are involved in the formation of the synaptonemal complex
have homologues from yeast to mammals. So, a synaptonemal complex is not only
evolutionary conserved structure it is also functionally conserved.
We have also seen that during anaphase one, after the DNA recombination is complete the homologs
need to segregate from each other. Therefore, the timely loading of these proteins to the chromosome
axis is essential for assembly of the synaptonemal complex and the timely removal of these proteins
from the chromosome axis is absolutely essential for the disintegration of the synaptonemal complex
in order for the homologs to separate during anaphase one.
Now that we understand the structure of the synaptonemal complex, let us look at the dynamics
of the synaptonemal complex in budding yeast in context with the different stages of meiotic
prophase 1. What is shown here in white are two sister chromatids from one homolog in the pair,
and what is shown here in blue are two sister chromatids from another homologue in the pair.
Chromatids from two different homologues in the pair are called non-sister chromatids,
and recombination is biased towards recombination between inter-homolog rather than inter-sister.
During the zygotene stage we know that the synaptonemal complex assembly starts
by loading up the proteins that we just saw. During pachytene stage, the synaptonemal complex
assembly is matured and the two homologues are brought close together and crossing over occurs.
Now in order for the homologous chromosomes to segregate during anaphase one synaptonemal
complex disassembly is equally essential and this is brought about by removal of the proteins
that were involved in maintaining the synaptonemal complex here.
The synaptonemal complex disassembly is brought about during diplotene and diakinesis stage.
In case, the synaptonemal complex disassembly does not occur properly, it can lead to a situation
where one of the daughter cells would get an abnormal number of chromosomes
or one of the daughter cells would not get any chromosome at all
and such situations are called situations of non-disjunction.
Approximately 10 to 30% of fertilized human eggs contain an abnormal set of chromosomes,
and this is a result of non-disjunction of chromosomes during meiosis. Non-disjunction
or mis-segregation of chromosomes can occur either during meiosis 1 or during meiosis 2.
You would recall that during meiosis one homologs are the ones that segregate.
While in meiosis 2 sister chromatids are the ones that segregate to the opposite poles.
Now in a normal scenario in the meiosis one the two homologs segregate two opposite poles
and the two sister chromatids segregate to opposite poles in meiosis 2 normal
situation. When non-disjunction or mis-segregation occurs,
what happens is, for example in case of true non-disjunction the two homologues,
which are paired together are segregated towards the same pole, which leads to aneuploidy.
Similarly, in achiasmate non-disjunction, which happens during meiosis 1, the homologues which are
not actually paired together, segregate towards the same pole which again leads to aneuploidy.
There can also be a case of premature separation of chromatids during meiosis 1, which could lead
to polyploidy in one daughter cell and aneuploidy in one cell. Both of these cases of aneuploidy
and polyploidy are deleterious to the organism. In case of meiosis 2 if non-disjunction occurs,
which means that the two sister chromatids did not separate from each other as should be, and
both of them are segregated towards the same pole leading to aneuploidy. Aneuploidy and polyploidy
result in either miscarriages or result in genetic disorders.
Coming back to the primary question,
which is, if the siblings have the same parents why are they different from each
other and how does this exchange of genetic material occur between the chromosomes? The
answer to both of these questions lie in a process called homologous recombination and
we will be elaborating on the mechanistic process of homologous recombination in the next segment.