All language subtitles for 97031x_MH_Mapping_Linkage_05_Recombination_Rate_v2-en

MICHAEL HEMANN: So what does that mean?

I mean, what does it tell us that they are 8 centimorgans

apart?

And how does that bring us any closer

to understanding whether they could

be in the same gene or not?

Well, recombination rates vary between organisms,

which is to say, in some organisms,

lots of recombination occurs in a very short region,

whereas, in others, recombination occurs rarely.

And so it occurs as an infrequent event

over a really long stretch of DNA.

And so we can actually couple this idea

of a genetic distance, a centimorgan distance,

with a physical distance using this formula.

So genetic distance, which is measured in centimorgans,

equals physical distance--

and physical distance will be in megabase pairs,

so in, essentially, million base pair units--

times a recombination rate, which will be in

centimorgans over megabase pairs.

So this recombination rate is going

to vary between distinct organisms.

So, in Drosophila flies, recombination rate

is 3.3 centimorgans per million base pairs.

In humans, it's 1.3 centimorgans per million base pairs.

So there's more recombination in flies

than there is in humans per the same unit distance.

In yeast, it's actually 360 centimorgans

per million base pairs.

So there's a lot more recombination in yeast.

And, if you look at other organisms like bacteria

or viruses, the recombination rate is much, much higher.

So, generally, the simpler the organism--

or single-celled organisms have much higher recombination rates

versus multicellular organisms.

And more complex organisms, like humans,

have some of the lowest actual recombination rates.

So, for viruses, they actually shuffle up their genomes

really, really rapidly and efficiently,

which can be sort of a scary thing

when thinking about adaptation or the generation

of new characteristics when they combine with other viruses.

OK, so we have this different inherent ability of DNA

to recombine in different species.

We also have different sizes for genes in different species.

So let's think about the largest genes

in each of these organisms.

So, in Drosophila, the biggest gene

is about 0.1 million base pairs.

So it's about 100 kilobases is the biggest gene.

In humans, we have some really big genes.

So we have genes like dystrophin and titan.

And so our biggest gene is around 2.3 million base pairs.

We have lots of introns in genes.

So very little of it, as a percentage,

is actual coding sequence, but they stretch out

over really a long distance.

And all of that is space where recombination can actually

occur.

And so, in yeast, the biggest gene

is about 0.005 billion base pairs, around 5,000 bases,

again, because yeast really don't have very many introns.

And so the space is a lot more contracted.

So, to get recombination in a gene,

you actually need this very high recombination rate

that's present in yeast.

So we can calculate the genetic size for each of the biggest

genes here.

So, in yeast, the genetic size of the biggest gene

would be 0.005 megabase pairs times 360 centimorgans

per megabase pair equals 1.8 centimorgans.

For humans, we have 2.3 megabase pairs

times 1.3 centimorgans per megabase pair

equals around 3 centimorgans.

And, finally, in Drosophila, we have the biggest gene

is around 0.1 million base pairs.

There are 3.3 centimorgans per million base pair.

So the biggest gene is around 0.3 centimorgans.

So is it possible that these mutations are in the same gene?

All right, so we've calculated that the overall distance

between these two is 8 plus or minus 2.8.

So, at the low end, we have 5.2 centimorgans,

which is really much greater than 0.3 centimorgans.

So these are quite a distance apart.

And so it is unlikely that they're,

in fact, in the same gene.

This size is sort of much too big.

And so you can imagine that, if mutations

are in the same gene--

like you have this maximum distance of 0.3 centimorgans.

And so what does that say about the kind of cross

that you would have to do?

I mean, so, if you're looking at 0.3 centimorgans,

if we have 100 times the number of crossovers

over total gametes equals 0.3, what

it says is that you actually have to have a lot of gametes

that you're looking at.

You need to have--

you need to have a lot of meiotic events

because you're only going to get this very small number,

this 0.3, out of 100 gametes.

So you need to actually have very large numbers to be

able to see a recombination event that is

localized within the same gene.

And so the closer things are linked together,

the more meiosis you need to actually interpret

actual genetic distance.

So, before, when I said that crossovers may not appear,

they may not appear if they're really tightly linked

unless you have tons and tons and tons of progeny,

which you can generate if you're using model organisms.

It can be more difficult when you're

looking at human pedigrees and establishing

genetic distances to figure out the exact spatial relationship.

But the whole point of all of this

is that we actually want to be able to start tying together

different phenotypes and different genotypes

on the same chromosome.

So we can identify map distances between two genes or three

genes.

We can look at all of these sort of pairwise interactions.

And we'll talk about how we look at, perhaps, three genes.

But we're able to actually orient them

relative to one another and provide

a specific genetic distance between two of them.