And then the good ones are AA and Aa, right.
What happens is it gets very rare,
almost all of the little as are present in the heterozygous form.
So they're basically masked and selection doesn't get rid of them very well.
Only the very small number of aa are actually being eliminated by
natural selection.
So the better dominant allele never quite gets to fixation.
Now a lot of diseases, as I mentioned way back when, tend to be recessive.
And as a result these mutations causing disease will stick around
within populations but never fix, and they eventually do get lost, but
it takes a very long time for them to get lost.
So this is a variation that you'll see that will stick around within the species
and it effects the within the species numbers,
but does not effect the between species numbers.
And these diseases will tend to be associated with non synonymous
bad variations, so this is what causes that.
Essentially, here's the ratios again we talked about,
between species nonsynonymous over synonymous versus within species
nonsynonymous over synonymous.
That if all nonsynonymous differences were neutral we
expect these ratios to be similar.
If some of these nonsynonymous differences were advantageously selected then
we expect this ratio, A/C > B/D.
Right, because the advantageous ones would spread,
they would come between species non-synonymous variation.
In contrast, if you have maladaptive non-synonymous differences,
they will persist within species and
never be converted to between the species differences.
In that case A/C < B/D.
The that's what will happen if you have diseases lingering around.
So looking at the McDonald Kreitman test we have this A/C = B/D.
That's a case where you can't reject neutrality.
Again, it doesn't mean it's neutral, it can be a mix, but you can't reject it.
If A/C is greater than B/D,
then we have increased non synonymous changes between species.
We have more non synonymous changes than we expected between species relative to
within And that is indicative of positive selection or advantageous variation.
So you're running.
In contrast, if A/C is less than B/D then you have decreased nonsynonymous changes
between species.
What that means is you have some variation that's lingering within species and
doesn't quite get fixed.
That is often the result of negative selection.
There are other possibilities, things like overdominance that we talked about earlier
will also do this same sort of pattern.
But it's thought that over dominance is not especially common, so
a lot of this is going to be in the boat of negatives selection or
bad variations sticking around.
So what happens when we look at the genome?
I showed you a couple of examples.
This is looking at a lot of genes studied across or
the difference between humans and chimps.
The blue marked genes are ones that
have McDonald-Kreitman tests results indicative of positive selection.
The red ones are indicative of negative selection.
You notice there's a lot more red out there than blue.
But again, we know that most mutations are bad.
We know that most bad mutations are recessive, therefore,
it's gonna make it so they're just kind of lingering around.
So instead of just looking at this figure, let me give you some of the numbers.
The positively selected genes from that particular study I was just showing you,
there are about 304.
Again, what are they associated with?
The same sorts of things as the high dN/dS values, immunity protein genes,
gamete formation ones, also some for sensory perception.
In terms of negatively selected ones, many of these are involved in cytoskeleton
formation and they're often associated with diseases like, muscular dystrophy,
cardiovascular disease, etc.
So let me give you one to try here, so you can have a little bit of practice within
the video before you even try any of the practice problems.