Original subtitles

MICHAEL HEMANN: Chromosome segregation is actually

visualized and chromosomes were visualized over 100 years ago.

So again, over the turn of the 19th to the 20th century,

people like Theodor Bovari used microscopic techniques

that were emerging to be able to actually see the segregation

or the movement of chromosomes from one cell to the other,

or the separation of chromosomes as cells were dividing.

Now these were visualizable entities.

It wasn't clear at the time that these were actually

structures that contain DNA or genetic material,

although he did postulate that these did, in fact, contain

genetic material, but that was shown only a little bit later.

And you could see in a wide variety of organisms,

including human cells, that all of these organisms

had recognizable chromosomes.

They could all be visualized, and actually,

made some interesting observations that in cancer

cells, like here on the bottom right,

you actually saw missegregation of chromosomes.

So you saw chromosomes that weren't

neatly segregating into two daughter cells over mitosis.

And that turns out to be really a characteristic of mitosis.

So on the left here, we have chromosomes

from a normal cell--

so a normal human, if there's such a thing as a normal human.

So this is a female with two X chromosomes.

These chromosomes have all been stained with a technique called

spectral karyotyping, which uniquely labels

each chromosome with a specific color,

so it's a good way to kind of map all of chromosome content.

And so on the left here, we have a normal cell.

On the right here, we have a cancer cell.

This is one cell, and it has this colossal number

of chromosomes--

so too many chromosomes, lots of reorganized chromosomes,

translocations, missing pieces.

And again, this is something that

was known over 100 years ago to be a characteristic of cancer

cells that not only did they have lots of chromosomes,

but they don't segregate their chromosomes really properly.

So what are chromosomes?

Well, as you know, chromosomes are

a mixture of DNA and proteins.

So DNA is wrapped around histones,

which not only compacts DNA, but also regulates

the transcription of genes.

So it makes genes-- some genes off and some genes off.

In a nucleus, it really looks like, during most of the cell

cycle, a big bowl of spaghetti.

So DNA is really filling the nucleus.

It's really spread out.

Even though it's still bound to histones,

it's really disseminated throughout the entire nucleus--

again, still compacted with nucleosomes.

In the course of mitosis, you get condensation

by many orders of magnitude into these recognizable chromosome

structures, shown here to the right, where we're

looking at two sister chromatids, so

two replicated pieces of DNA, two double-stranded pieces

of DNA, that have a centromere which, in most cases,

is in the middle of a chromosome,

although not always.

I mean, it's called a centromere because it's

sort of in the middle, but chromosomes can have

centromeres towards one end.

They can have them at the very end.

In fact, all of mouse chromosomes

are telocentric, meaning that the centromere is really

at the very end of all of their chromosomes,

next to the telomere, which is a chromosome end structure.

So the telomere is a repeat sequence

that essentially caps the end of a chromosome

and protects it from degradation.

It allows for the complete replication of the chromosome.

Now these chromosomes are going to become visualizable

during mitosis and in metaphase, where

you have this condensation, which

is really essential for the segregation of these

into subsequent daughter cells.

So we talked a little bit before about TH Morgan

and Drosophila eye color.

So red color is wild type, and white color is mutant.

Really, the cool thing about this eye color

was not just that you could actually--

he could identify mutants and was really the first instance

in a multicellular organism of the clear identification

of a new mutant, but also, that it could be mapped

to a particular chromosome.

So we know from past lectures that this is an X-linked trait.

And so, for the first time, you could actually

map a particular phenotype to a particular chromosome to the X

chromosome, or an alteration on the X chromosome.

And this discovery in a lot of ways

placed genes onto chromosomes-- introduced the idea

that these segregating units were actually segregating

phenotypes, and that the gene may

be a physical entity on a physical structure in a cell.

And certainly, in retrospect, is looked

at as really the first clear example of mapping

a gene to a physical unit.

Subsequently, we've mapped a lot of phenotypes

onto different Drosophila chromosomes,

largely based on the ability to see that these are actually

segregating in different ways, or independently

from one another.

So if a gene is actually independently segregating

from one another, it suggests that it's actually

on a distinct chromosomes.

Now this can also occur if it's far enough

away on the same chromosome, and we'll

talk about recombination distance and linkage studies.

But essentially, using this approach,

we could start placing genes on chromosomes.

So what do chromosomes look like in different organisms?

Well, on the top left, we have people.

So people have two copies of 23 chromosomes.

This includes the X and Y chromosome,

which we count sort of as one chromosome,

or two versions of one chromosome,

although they're substantially different.

As you can see, chromosomes are numbered

based on decreasing size, with the exception of the sex

chromosomes.

So chromosome 1 is the biggest and chromosome

21 and 22 are the smallest.

In this case, these are stained with Giemsa stain, which

recognizes, essentially, condensed and decondensed

chromosomes.

And for years and years and years,

people that do karyotype analysis or chromosome

analysis in hospitals can easily recognize chromosomes

not just by their length but by their banding patterns.

So they can recognize translocations or movements

of different chromosomes or loss of different chromosomes

simply by this simple banding pattern and their ability

to really recognize lots of details in this banding

pattern.

Now there's not a very good correlation

between chromosome number and DNA content.

So yeast have 16 chromosomes.

This animal over on the right, here the muntjac

which has a genome that is roughly

the size of the human genome actually

only has three chromosomes, so it

has two copies of three chromosomes,

so we see a total of six chromosomes here.

And as you might expect, these chromosomes are huge.

They're really, really big.

They're the size of six of our chromosomes or so.

So as we speciate, we develop different chromosome content

and different chromosome sizes.

An example of this is shown here.

Here, we're looking at a comparison of human chromosomes

and chimpanzees' chromosomes.

And I think at first glance, what

you can see is we're pretty similar to one another

with very few exceptions.

I mean, if you look at some of the length

of these chromosomes, you'll see some differences

and some differences in the length of the short arm, which

are on one side of the centromere

and the long arms which are on the other.

But there's a major difference here,

and that is, instead of our one chromosome 2,

the chromosome material in chimpanzees

is actually separated onto two distinct chromosomes.

And this happens during speciation.

That happens during evolution.

And the development of new chromosomes

actually makes it very difficult to, then, interbreed.

It creates real problems in meiosis.

And as we'll see, it's the ability

of chromosomes to really synapse properly

that allows them to be segregated properly,

and so if you actually try to synapse two chromosomes to one

chromosomes, you end up with significant problems.

So this actually underlies a lot of sterility

that we observe if different kinds of species

mate in their F1 generation because they're

unable to undergo proper meiosis.