Lec 7 - How is Genetic Material Inherited? Part 1

Gene Regulation in Eukaryotic Cells

Mechanisms of Gene Regulation:
- Epigenetic Control: Chromatin remodeling.
- Transcriptional Control: Utilization of silencer or enhancer elements that regulate RNA polymerase access to the transcription start site.
- SIRNAs and MicroRNAs: Methods to inhibit mRNA synthesis into protein.
- Translational Control:
  - Involves untranslated regions (UTRs) of mRNAs, which include the 5-prime UTR (5' UTR) before the AUG start codon and the 3-prime UTR (3' UTR) after the stop codon.
  - These UTRs do not encode protein but regulate translation and can lead to mRNA degradation.

Iron Metabolism Regulation

Iron Response Element (IRE):
- Located in the 5-prime UTR of ferritin mRNA and the 3-prime UTR of transferrin receptor mRNA.
- Ferritin: A protein that stores iron.
- Transferrin Receptor: Mediates iron uptake from blood into cells.
IRE Binding Protein (IREBP):
- Binds IRE under low iron conditions, blocking mRNA translation by obstructing ribosome binding to the 5' cap or destabilizing the 3' UTR.
Low Iron Conditions:
- Ferritin mRNA translation is blocked to prevent unnecessary iron storage.
High Iron Conditions:
- IREBP undergoes a conformational change and cannot bind IRE leading to destabilized transferrin receptor mRNA, decreasing its lifespan.

Cell Division and Mitosis

Cell Cycle:
- Comprises phases: G1 (Gap 1), S (Synthesis), G2 (Gap 2), and M (Mitosis).
- Most of the cell's life is spent in the interphase (G1, S, G2), with a brief phase in mitosis.
Phases of Interphase:
- G1 Phase: Preparation for DNA replication.
- S Phase: DNA replication occurs, leading to duplicated chromosomes.
- G2 Phase: Prepares for mitosis, expanding cell size and increasing protein production needed for division.
Mitosis:
- Results in two identical daughter cells, each with the same number of chromosomes as the parent cell.
- Phases include prophase, metaphase, anaphase, telophase, and cytokinesis.
Drugs that Affect Mitosis:
- Colchicine disrupts microtubule assembly, preventing spindle formation which stalls cells in prophase.

Meiosis

Meiosis: Produces gametes with half the number of chromosomes.
Phases: Similar to mitosis, but with two rounds of cell division (meiosis I and II) and crossing over occurs in prophase I.
Sex Chromosome Distribution:
- Humans have X and Y chromosomes, while reptiles often have Z and W.
- During meiosis, X and Y (or Z and W) segregate to ensure gametes are produced with the correct chromosomal composition.
Genetic Variation:
- Crossing over and independent assortment during meiosis create genetically distinct gametes.
Parthenogenesis: Reproduction without fertilization, as seen in certain reptiles.
Case Study: A female rattlesnake gave birth without mating, leading to investigation into meiosis errors (nondisjunction) resulting in a male offspring from parthenogenesis.

Okay, good afternoon.

Last week we had talked about gene regulation in eukaryotic cells, and I started to discuss a variety of different mechanisms by which we can control gene expression in ourselves, including things like epigenetic control, where we can remodel chromatin, transcriptional control, where we can use it as silencer or an enhancer to be able to regulate whether or not RNA polymerase has access to the transcriptional start site.

We talked about SIRNAs and microRNAs as other means by which we can shut down a particular mRNA synthesis into protein.

And then finally we came upon to set up a system which regulates iron metabolism in eukaryotes in our cells, actually, that we use a type of translational control that involves features of the mRNA itself that don't belong to the region that is translated to protein.

In other words, it involves what we call the untranslated regions of mRNAs, and that can be in the 5-prime untranslated region or 5-prime UTR ahead of the initiator AUG, or it can be in the 3-prime UTR on the other end after the stop codon in the mRNA.

So these regions of the mRNA while are part of the transcript are not encoding the actual protein.

So they form a way for us to be able to regulate the means by which we would either synthesize this mRNA into protein through the process of translation that we talked about last week, or we would somehow inhibit that translation, or worse, we might actually degrade this mRNA so that we don't produce the necessary protein product.

So those are all mechanisms by which we can enforce translational control over these proteins.

So the system that we set up was one of the iron response element, and the iron response element is a feature of the 5-prime UTR of the ferritin mRNA, and of the 3-prime UTR of the transfer and receptor mRNA.

Ferritin is the storage protein, and the transfer and receptor is the protein that involves entering or receipt of iron from our bloodstream all the way into cells.

These particular response elements are bound by proteins that we call the iron response element binding protein.

And if you notice its structure under normal circumstances, its shape fits these two elements perfectly.

But in the presence of high iron, they bind to this protein, and the protein's confirmation changes in such a way that it will not be able to occupy either the 5-prime UTR or the 3-prime UTR of these two different proteins.

So obviously this has consequences for the way that each of these mRNAs is regulated, and those consequences actually are completely different in terms of the actual output for each of those mRNAs.

So I want us to kind of explore those elements together, so if you will use your clicker here, and let me know which of the cartoons best represents ferritin mRNA under low iron conditions.

So if you want to know more about ferritin mRNAs, you can find the link in the description box below.

If you want to know more about ferritin mRNAs, you can find the link in the description box below.

Okay, so the responses indicate that basically everyone's guessing.

So I suggest we go over this in some detail so that we're no longer guessing.

So first of all, I'm asking you about ferritin mRNA, and ferritin is the storage protein that stores iron safely inside cells.

Does ferritin mRNA have a 5-prime UTR element or a 3-prime UTR element?

5-prime UTR element, yes.

I also mentioned that we are under low iron conditions, which of the two letters describes the situation in low iron?

A and C, exactly. So we've got the iron binding protein that is able to attach to these structures because we do not have iron bound to it, and under low iron conditions that would be the fate of those proteins.

So we said that the ferritin mRNA has a 5-prime UTR, so of course then this would be the correct answer, would be A.

Okay, so under low iron conditions, we have this situation of A that we said, where we've got the IRABP or the binding protein affixed to this 5-prime UTR ahead of the AUG,

which basically means what you're doing is you're putting a giant thing in the way of the small subunit of the ribosome, which was supposed to attach to the 5-prime cap and start scanning for the AUG.

No way that small ribosome subunit is getting past this giant thing that's in the way now.

So basically what we've done is we have stopped or blocked translation simply by putting a giant protein in the way of the ribosome, and this is because there's very little iron in the cell.

If there's very little iron in the cell, we have no business really making an iron storage protein or ferritin.

It doesn't make sense to make an iron storage protein when there's nothing to store.

So the regulation here is simply to block translation of the mRNA that would create the storage protein.

If the iron levels were to dip, then we would of course have a situation or increase in some way.

We would have a mechanism of regulation to go either way.

In this case, we've got a low iron, so we act a certain way to not bother producing ferritin.

If we had high iron, we would think about making ferritin because that's the storage protein that's going to store iron safely.

So we have a mechanism to basically go back and forth.

Now let's consider transfer and receptor gene, and this one has an IRE, the three-prime UTR of the mRNA, and that three-prime UTR also has these instability elements that are found within that particular structure.

So I want you to tell me, under high iron conditions, which of the following would be true?

I'm not sure.

Okay, so it looks like there's some confusion between the top.

So the bottom choice option C we can basically rule out right from the get go.

I'm basically telling you that there's something about the instability elements that just become ineffective under one condition or the other, and that's just never the case.

So there's nothing ineffective about this binding protein whatsoever in its function, so we rule out C.

So the question is between A and B. So here what I'm saying is that in A, the lifespan of the mRNA is increased in the condition where high iron is high, or in B I'm saying the lifespan of the mRNA is decreased when iron is high.

So first of all, we need to envision in ourselves the binding protein and what happens to it when iron levels are high.

So when iron levels are high and it can bind to the binding protein, what is the structure of the binding protein? Can it engage the mRNA or not?

No. Okay, there's a lot of shaking of heads. No. Okay. So no, it can't bind the mRNA because it is misshapen.

It is not in the confirmation that we'll engage with the transfer and receptor mRNA.

So that's one thing, which basically means that that mRNA is left to its own devices.

But this is a transfer and receptor mRNA that has a 3 prime UTR, and that UTR, if it's not covered up by something, actually has something called instability elements,

which means that the cell will look at that and go, oh yeah, I need to chew up this mRNA.

So it will actually decrease the lifespan of that mRNA if there's no protein bound to kind of shelter it from those instability elements being visible to the cell.

So in other words, when iron is high, we destabilize the mRNA for transfer and receptor, which means we don't bring in any more iron into the cell.

And that makes perfect sense, right? We've already got a ton of iron inside the cell. Why would we make proteins to bring in more iron?

We should be in the business of just storing whatever iron we have, not bringing in additional protein or additional iron.

So in this case, the transfer and receptor mRNA becomes unstable and it's degraded over the course of time so that no protein product is actually made.

Okay, so if we were to look at this in terms of the answer, of course, here then is B because we're decreasing the lifespan of the mRNA.

And if we look at what's actually happening in the context of cells, what we would see is that under high iron conditions, you have a misshapen, IREBP,

it can no longer engage with the 3 prime UTR, and the 3 prime UTR now reveals instability elements, those are the yellow patches,

which means the cell is able to look at this mRNA and say, oh yeah, I'm going to degrade this mRNA.

And actually reduce its lifespan inside the cell so that no protein product is made at that time.

And this makes sense because we've got a lot of iron, we don't need to synthesize a protein to bring in more iron.

So by switching the states of this particular burning protein, we're able to carefully regulate whether or not an iron storage protein

or a protein receptor that's involved in bringing in iron are properly translated in cells.

So this is a classic example of what we refer to as translational control with the UTR elements being binding sites for a iron response binding protein.

Okay, so this is sort of a foundational concept and I want to make sure that everybody understands this particular concept in some detail.

If you're struggling with any aspect of it, please make sure to come to office hours and ask questions.

This type of translational control happens for pairs of protein for like 500 different genes in our systems.

So this is just one example to illustrate the kind of prevalence of this particular type of gene expression control that we have in UTR.

So with that, I want to move on from central dogma discussions that we've kind of spent some time on to now discussing inheritance.

So for that, we first need to kind of understand cell division itself and we hopefully all of us remember that cell division is critical for us in terms of both development, cell replacement, growth, healing, etc.

But also for the process of reproduction in the simple instance where we're simply replacing cells in the process of growth or renewal or repair.

We go through a cell cycle and not cell cycle culminates in divisions of a single cell into daughter cells that we call mitosis or M phase.

But that mitosis or M phase is a very brief instant in the life of a particular cell.

Between mitotic divisions, the cell spends a lot of time in these other phases that we refer to collectively as interface.

So interface is where most cell spend most of their time.

Let's say 10 to 14 hours of an average cell is spent in interface and maybe about 30 minutes to an hour is spent in mitotic division.

So in interface, we've got multiple stages that we go through for preparing for the next mitotic division.

And those can be kind of grouped as follows.

The first is G1 phase or the gap one phase where the cell is effectively preparing itself with the process of duplication of DNA.

So it upregulates all types of factors that is involved in the next phase of interface called S phase where we will duplicate the DNA.

So everything we talked about it with regard to DNA replication and all of those proteins engaged in the process of pulling apart the parental strands and duplicating them are all being increased in expression in gap one phase.

Then we go through the process of S phase where we actually duplicate our DNA.

And then we go into gap two or G2 phase where the cell actually physically expands in size and then starts to upregulate all of the proteins that it needs in order to go through the mitosis or M phase.

And there you would see, for example, cytoskeletal elements like the spindle apparatus, which is made up of microtubules, those proteins will be upregulated during G2.

G0 is a phase that we kind of interchangeably use with G1 because there are some cells that are in resting or G1 equivalent phase but are not actually actively preparing for S phase.

So they have kind of exited the cell cycle to some extent. It's not that they might not return into the cell cycle, but at the time there's sort of a differentiated cell that is not preparing for mitotic divisions.

So we refer to that type of resting as G0 phase. So our DNA as I showed you in the very first lecture of this module is organized into autosomes and sex chromosomes.

And we have 23 pairs of those and they are homologous in that we have contributions from both the paternal and the maternal gametes from in the embryo.

So just so we make sure that we're all on the same page. I want to go through a few clicker questions here to understand the complement of our genome.

So here the chromosomes that are circled could both be chromosomes from the same parent. Now I want you to tell me whether that's true or false.

Okay, that's great. So most people think that the answer is B or false and that is in fact the correct answer.

Mostly because all we're looking at here in the circled area is a pair of homologous chromosomes. And of course each of these homologues has doubled because it has gone through S phase, which is why there are sister chromatids joined together by a centromere.

So this has gone through S phase, but this single chromosome with the two sister chromatids is the contribution of one parent and these two sister chromatids held together by the centromere are the components from the other parent.

So together each of these represents the autosomes that are contributed by each of the two parents and therefore not from the same parent.

Okay, so that type of arrangement of our chromosomes is what I need you to envision when I mentioned this process of duplication of DNA during S phase.

So what we have ahead of S phase is one chromosome from each of the two biological parents which after undergoing DNA replication becomes a set of two linear DNA molecules that are joined together by a centromere.

And we now have two homologous chromosomes each that has been duplicated during the process of S phase.

Okay, let's do a couple more.

Which circled region contains two identical pieces of double stranded DNA? And if you think none of the circled ones actually are identical pieces of DNA, then select E.

Okay.

So there's a little bit of confusion between options C and D. Most people agree that A and B are not what we're talking about in terms of being identical pieces of double stranded DNA.

So A, of course, is one we've already discussed. They are homologous chromosomes that have been replicated during S phase.

So two parental contributions that cannot be two identical double stranded DNA pieces.

This here is chromosome four, one of the homologs. And then this is chromosome 11, one of the other homologs. And so those two obviously would be an entirely separate types of DNA with different genes on them.

So the confusion here is between these two. So in this particular case, we've got C, which is one of chromosome seven homologs, which means that the row of genes of one of these has been duplicated to create the other sister chromatin.

So these would be identical copies of each other. So this would be sister chromatids that are identical replicas.

In this case, we've got two homologs and what is highlighted are these two sister chromatids, but those are what we would call non-sister chromatids because they are chromatids from each of the different parental homologs.

So for instance, on the left side, this could be the maternal contribution and on the right side, that's the paternal contribution. So what's being highlighted in the box is one of the maternal and one of the paternal contributions.

And each of those would have a different arrangement of alleles of the genes present on that chromosome so they would not be identical pieces of DNA.

Great. So of course, then the correct answer in this case would be C, which is copies of one of these strands copied identically and held together at the center of the year.

Okay. So all of this is happening during that process of S phase. And after S phase, we go through a gap to phase where we are now going to prepare for mitosis or cell division.

I'm not going to go into the details of mitosis in this particular case because I'm going to rely on the fact that most of you are well versed in understanding the steps involved in mitosis.

If you're not, I would suggest that you please review the figure that's noted on this particular slide.

And all of these different phases in pro phase, all the way to telophase and then cytoplasmic division, which is what we call cytokinesis, is the result of mitosis that basically takes the duplicated DNA and splits them across two daughter cells, which now have the identical number of chromosomes as the parental cell.

To give you an idea of the type of detail I expect that you retain about mitosis is that I would, for example, want you to know that at pro metaphase, we have these duplicated chromosomes attaching to the spindle apparatus.

And I would want you to know how they're attached to the spindle. The spindle is composed, of course, of microtubules. Those microtubules attach to protein called the kinetic core.

The kinetic core lies on either side of the centromere that holds together the two sister chromatids. In other words, each of these chromatids has its own kinetic core.

And those kinetic core proteins can attach to spindles from opposing poles that are being created in the context of cells.

So I do want you to know what happens in each of the different steps of mitotic division. And I want you to know that the products, of course, are that we have two identical daughter cells and each daughter cell contains the same number of chromosomes as the original parent cell.

Now, this diagram, as I mentioned, is for your review. But here, all I'm going to point out is that in mitosis, we begin, of course, by condensing our genome. There's no gene expression happening here.

We want to be able to split this DNA, duplicated DNA across the two daughter cells. We have to get rid of the nuclear envelope, and we have to develop a spindle.

So that's the initial setup, which is in pro-phase. Pro-metaphase is what I just described where the spindles now start to connect with our actual chromosomes. Then at metaphase, we line up those chromosomes in a single file in the middle of the cell that's sometimes called the equatorial plane.

And then in metaphase, we pull apart the two sister chromatids by shrinking the spindle to the edges of the cell. And then finally, in telophase, we reform the nuclear envelope, and we decondence the DNA in each of the two emerging daughter cells. And then cytokinesis will actually cut down the middle to create two new daughter cells.

Okay. Just so we are all on the same page about how this works, let's do a question here. So I'm telling you that I have a drug called colchocene, and this drug blocks the assembly of microtubules, microtubules, of course, build the spindle apparatus.

And if I add colchocene to dividing cells at what stage of mitosis would you predict that these cells will arrest as in be stalled in cell division?

I'm sorry that it's sending you the wrong slide each time that I do this. So alert me if that happens again. I don't know that I can fix that right now, but hopefully having this up on the screen works.

Okay. So we've got a 50-50 split again, and this time the 50-50 split is across A and B.

So remember that we just talked about the details of pro-metaphase, which is the phase between pro-phase and metaphase, and at pro-metaphase I said that we have to have the spindle actually attach to the chromosomes, and then at metaphase you line up the chromosomes in the middle of the cell.

So here I haven't listed pro-metaphase, but pro-metaphase would just not happen if I've disassembled the spindle, which basically means that every one of the cells will just be resting in pro-phase because there's no ability to create a spindle to first attach to the kinetic wars in pro-metaphase, and then to be able to line them up in metaphase.

So the cell would never be able to get to metaphase, it would be stalled in pro-phase, because the answer here would be A.

Okay. We've gone through S phase before we go through mitosis, so a skin cell, which is a somatic cell, not a germ cell, will go through mitosis.

When it's in G2 after S phase, how much DNA does this particular skin cell have as it did in G1?

Okay. Everyone thinks twice as many, and that would be correct. So in this case, be careful the type of cell that I'm actually alluding to in every case, so if it's G1 or G2, whether it's a somatic cell, whether it's a germ cell, whether it's a cell undergoing mitosis or a cell undergoing myosis.

And that's kind of the setup for me to kind of get into the comparison between mitosis and myosis, and I will spend a little bit of time talking about myosis because I find that that's an area of actually a little bit of misconception in first year, so I will go through the myotic cell divisions, but know that the parallel in terms of mitotic cell division is that all of the phases of myosis are named identically, just the way that they're named mitosis, and the same activities happen.

There are many issues that we have myosis one and myosis two, but there's only one DNA replication for both sets of cell division.

So myosis is the business of producing gametes, so these are the cells or germ cells as we refer to them, eggs or sperm.

Each daughter cell contains half the number of chromosomes as the original parent cell, and this is required because fertilization in the species requires the combination of gametes from the biological male and the biological female to restore the full complement of chromosomes.

Each daughter cell is also genetically unique, and this is one of the ways in which the myotic cell divisions differs from mitosis is in the way the homologous chromosomes actually interact with each other during that first division.

So let's look at some of the details.

So prophase here, similar to how we set up in mitosis, will involve us condensing our chromosomes so that they are actually visible, getting rid of the nuclear envelope, and then we're able to see how the homologous chromosomes are actually lined up.

And this is a fundamental difference between myosis and mitosis is that immediately you're able to see that the two sets of homologous chromosomes are not going to line up single file in order to meet the spindle after the nuclear envelope breaks down, but instead they actually pair up together.

So we have the homologous chromosomes sitting side by side together as opposed to in single file, and this side by side interaction is often referred to as a byvalent, and these byvalents allow the possibility of exchange of information between the two non-sister chromatids.

So that's what we refer to here as crossing over, and the structure itself is called kiasma.

So here we have one homologue, here's the other homologue both have been duplicated during S phase, instead of lining up single file where this light blue one would normally be underneath the dark blue one if they were lining up for mitosis, they're actually lining up side by side here for myosis one, and therefore you now have exchange of information between the two sister non-sister chromatids in this case, and that creates a set of alleles on each of these two chromosomes.

That is completely genetically unique, it is neither the order of the maternal homologue nor the order of the paternal homologue, it is a mixture of the two.

But note however, that the other two sister chromatids are non-recommonent, so those, this dark one right here, and this light blue one on the end are both non-recommonent chromatids.

So we have two sets that are recombinant, and two sets that are non-recommonent.

Okay, so this mixing up of information is allowed by that alignment of the two homologs next to each other in pro phase of myosis one.

When we then, after this, go into nuclear breakdown, we're able to then go into pro metaphase and metaphase, where the spindle apparatus that's now formed can start to make contacts with the kinetic cores of each of these bivalids.

And notice here that they start to line up by the time metaphase comes, they are lined up one under each other in order to be able to pull apart to the different poles of the cell.

Once again, these kiasma or the exchange of information allows these two homologs to be side by side with each other when pro metaphase begins.

After this, we go through anaphase and telaphase, and we actually separate out the homologs from each other.

So the paternal and maternal homologs have now been separated into two daughter cells at the end of myosis one.

We then go through the same thing from myosis to all of the steps of the same only thing of note, we do not duplicate our DNA.

There's nothing that we're doing that regards S phase.

We just start with where we left off in myosis one and we go through the cell division process again, which basically means now we line everybody up single file.

This looks an awful lot like mytosis.

And then at the end, we pull apart the two sister chromatids in anaphase and we end up with four daughter cells, each of which has half the number of chromosomes as the original parent.

So myosis two here involved us lining up our individual duplicated chromosomes in single file and being distributed across the two.

However, in myosis one, sorry, myosis one, we had the homologs lined up next to each other and the whole chromosomes being separated across the two daughter cells.

So homologs together and here the homologs have been separated across the two daughter cells and we just pull apart the two sister chromatids in this case.

But side by side comparison here is mytosis, hopefully that you're familiar with where we start with a duplication of the original set of chromosomes and we simply pull the sister chromatids apart at the end of mytosis.

So everybody lines up single file here.

There is no affinity for the different homologs to each other.

In myosis we have affinity of the homologs, we have exchange of information between the homologs and we go through not one, but two sets of divisions to create four daughter cells with half the number of chromosomes.

This makes it sound like on the right we've gone from the original parent cell to four separate daughter cells, each of which will be a gamut.

This is the case in the biological male, each of those four daughter cells that are haploid will become four mature sperm.

In the case of the biological female, that's actually not true at all.

So even though we say we go from one cell to four gametes, we don't actually go to four gametes in the biological female, we just go to one gamete in the biological female.

One is after the first myotic division, we give almost all the cytosol of that original parent cell to only one of the two daughter cells.

Note that this daughter cell basically didn't receive any cytosol compared to the other one.

So it's basically just like a little trash can for the other set of chromosomes that we don't want in this particular daughter cell.

We go through the second round of myosis and again, in that second round, this one that had most of the cytosol generates two daughter cells of which only one gets all of the cytosol.

And that is the only one that matures into the oocyte or the egg cell, whereas the other three here are referred to as polar bodies and they do not become mature gametes in the biological female.

So cytoplasmic division controls one gamete production from one parental cell in the biological female and four gametes from one parental cell in the biological male.

Okay, so to review some of the steps of myosis, I thought we would go through a kind of an interesting case study for the remainder of the time.

And the reason I want to take you through this is because we've kind of focused on the idea of autosomes in being able to be split across these different gametes during myosis, but we haven't really considered what happens to the sex chromosomes when we separate them across the gametes.

So this is effectively a way for me to just review the concepts of myotic division involving both autosomes and sex chromosomes, but kind of tying it into an interesting story.

So the story begins here with a timber rattlesnake, that's the picture that's shown here on the slide.

And rattlesnakes are studied for a variety of reasons, animal behavior, not to be the least of our interests.

And the rattlesnake in particular can live 20, 30, 40 years in captivity quite happily in tanks and labs.

In this particular timber rattlesnake has a very fancy set of fangs here, and if it were to bite you, you would be in a lot of trouble.

And you would probably have to end up in hospital and have a whole bunch of antivenom pumped into you because it can be fatal.

But the cool thing about this rattlesnake is that it's one of the posters of the snake universe.

So it spends a lot of time doing exactly what that picture shows, which is sort of posing and showing off its fangs and rattling.

So everyone that's close to it has enough time to run away.

So most of the time, it's not really a major threat to us as humans.

So there is a hermitologist in this particular story who has been looking after a female rattlesnake for a long time.

And one thing that we know about female rattlesnakes is that they are what we call oboe viviperas,

which basically means they give birth, quote-unquote, to live wriggling snakes, but it's not a true birth the way mammals birth live young.

What happens here is that the males produce sperm, the females produce eggs, after mating, the sperm and the egg fertilize, create fertilized eggs,

which are actually incubated inside the female snake.

And it's those fertilized eggs that will hatch over time and then release the new progeny snake.

So it looks like the female snake is giving birth to a live snake, but realistically, the female snake is just incubating eggs, fertilized eggs that then hatch inside of the female.

Okay, so these are oboe viviperas. There's a variety of other organisms, other reptiles too, that do this in fish as well.

There are many examples of fish that do this kind of reproductive strategy.

So the surprise here is that after 20 years of keeping a female snake in captivity, this hermitologist comes into their lab and they recognize that in the tank all of a sudden is a baby snake.

And that baby snake is not just sitting there, it's also a designate, it looks like a male snake.

So there's no follow play here, there was no sperm that was added to that captive female snake, there was no contact with other male snakes in the lab.

It just seems like it's just sort of appeared overnight.

So the question is that this particular biologist then decided to study how could this be possible in terms of a reproduction strategy for that particular female snake or was it possible to be?

Okay, so that's where we go back to our production of gametes and fertilization.

So myosis here of course produces of course gametes with one set of chromosomes remember and there are four gametes in the case of the sperm and one big gamete in the case of the egg.

And of course that's what we use in fertilization to be able to produce these offspring.

So let's look at through an animation what happens to autosomes during the production of these gametes and then look at what happens to sex chromosomes when we produce these gametes.

Okay, so if we were to simplify the chromosome complement of these cells to just these two sets of chromosomes what we would happen have happened when we want to produce gametes is that we would now duplicate the DNA of each of these autosomes.

So we have sister chromatids all lined up then we would line up in the metaphase plate notice this is one way by which we can line up.

I've just lined up the large green with the small green it doesn't have to be this way we can also swap the order it's just 50% odds which gets lined up which way.

And then we separate those at the end of myosis one we've separated the homologs when made two daughter cells then we go through and we separate the two sister chromatids and we generate our four sorry our four separate gametes so these would be the possibility of the four gametes each of which are halfway that makes sense.

So this as a reminder if you you can also line them up so that you have green and blue mismatch so that was just another arrangement and it's 50 50 odds which way we go so I just wanted to show you that that was another possibility where we could also have four gametes that are developed this way.

And that's exactly the products of myosis right we either end up with these four gametes here each with the different color of the two chromosomes that we separated or the same color of the two chromosomes that be separated.

So how about the sex chromosomes so in the case of us we have X and Y sex chromosomes and it turns out they do the exact same thing as autosomes they duplicate during as phase.

And there is a very small region right next to where we have the centrum years of the X and Y that's actually a small amount of complementarity between the X and Y chromosomes.

So there is a gene that sort of kind of has affinity for each other enough that the X and Y can actually line up the remainder of the genes are not shared between the X and Y chromosomes but because they line up this way they act just like any other homologous chromosome.

So we separate the two during myosis one and then during myosis two we separate the two sister chromatids and so you end up with 50% X bearings from or 50% Y bearings from.

So that for us is the mechanism by which we would then produce gametes in humans.

And most mammals would actually do it exactly the same way. So we've got X and Y which is what we call the heterogamedic sex so the two different sex chromosomes defines male development in mammals and the homogamedic sex or the two same sex chromosome bearing organism is biologically female in mammals.

Okay so we have this possibility it turns out with reptiles they do this slightly differently in terms of sex chromosomes has a different the heterogamedic sex and they have Z and W as their sex chromosomes the heterogamedic sex is actually female whereas the homogamedic sex so the two Z chromosomes is biologically male.

So they have a different type of sex differentiation that happens in reptiles. So the question here was after we've got Z and W in the female snake we would separate the Z and W after the end of myosis one and at the end of myosis two we would separate the Z chromosomes the chromatids from each other and the W chromatids from each other.

And these would be the possibilities to become the oocyte or in the in the female snake if all went to plan.

So the question is could there have been an error in the process of myosis that leads to this baby snake and turns out there is.

So you go through the first myotic division and you separate the Zs and Ws from each other but now at the second myotic division the spindle falls apart and now you have a process called non disjunction or you do not separate these two sister chromatids.

You go through myosis two and at the end of it you end up with one that has the two Zs and one that has the two Ws and then other two that just don't have any sex chromosomes which are of course non viable.

Turns out that having two W chromosomes is also not viable in this particular species because remember that the two Zs is male and ZW is female.

So this is non viable but this as a product of non disjunction and myosis two actually codes for male development.

So in this particular case we had an error in myosis in the female snake that led to non disjunction of the Z chromosomes which led to the homogamytic sex in that particular species which is biologically male.

So at the level of that second myotic division where we give one particular resulting daughter cell all of the cytosol to become an OSI was the staff at which there was an error in that original female snake.

So what we have here is an example of something that is actually quite prevalent in the animal kingdom and is called carthenogenesis which is reproduction from an egg without the need for fertilization.

So you effectively have an error in myosis two that leads to the full development of the next generation.

Okay so hopefully that was a good way to kind of think back to how myosis works and the separation of the homologs and the sister chromatids between both the regular autosomes as well as the sex chromosomes to then generate the next generation of species.

Okay so I'll stop there and then we'll pick up talking a little bit more about inheritance on Thursday.

Thank you.