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10. Evolution, Ecology and Behavior: Genomic Conflict
Poziom:
Temat: Edukacja
Prof: Okay,
today we're going to talk about
evolutionary conflicts,
and this is an area of
evolutionary biology that
contacts other disciplines,
including the Humanities,
in interesting ways.
I was reading Nature
this morning and there was a
review of an off-Broadway
production about the life of
Robert Trivers,
whose picture you're going to
see here,
and it was about Robert Trivers
as a disturbed young genius at
Harvard coming up with ideas of
conflicts of interest and
whatnot,
and the actor on the stage was
going on about how tormented the
young Trivers was,
and he was smoking pot and all
of this stuff,
and having his great ideas,
and upsetting the faculty at
Harvard,
and finally giving up in
disgust and going to Santa Cruz
and meeting Huey Newton and the
Black Panthers and all of that
stuff.
Okay?
And there was a guy in the back
of the theater who was chuckling
and came up and congratulated
the actor afterwards,
and he said,
"You got it just
right."
And it was Bob Trivers,
who was watching.
Bob's a professor at Harv--at
Rutgers now.
So we're going to be talking
about interesting stuff today.
And I want you to be aware that
the first part of it is
well-founded,
well-supported,
experimental science,
where the conclusions that I'll
present to you are quite
reliable.
And at the end of it,
I am going to go into some
speculative stuff,
where the conclusions aren't so
reliable, but it's very
interesting.
And I want to say that up front
so that--
and I'll give you a signal when
I transit from reliable stuff to
speculative stuff,
because I don't want you
thinking that the speculative
stuff is written in stone.
So let's begin by looking at
these plant flowers.
These are pPantago flowers.
Plantago is something that you
may very well have dug out of
your lawn.
It is a rosette plant.
It is a common plant around the
world, and it is gynodioecious,
which means that it has two
kinds of flowers.
It's got flowers that have both
male and female parts,
and it's got flowers that just
have the female parts and
greatly reduced,
or almost absent,
male parts, male sterile parts.
And evolutionary sex ratio
theory tells us,
in fact, that from the point of
view of the nuclear genes,
it's best to have a 50:50 sex
ratio and to be investing 50% in
male and female function;
and we will come to that soon.
However, in this organism
evidently, in some of them,
this 50:50 sex ratio has been
subverted, and all they do is
reproduce as females.
Now it turns out that the genes
that control this morphological
switch are in the cell
organelles;
they're not in the nuclear
genome.
The genes that are sitting in
the organelles in the cell,
be they mitochondria or
chloroplasts,
can only get into the next
generation through female
function,
through the eggs.
They are not transmitted
through pollen.
It is in their interests to
take the organism that they're
sitting in and turn it into a
pure female.
And you can see that
dramatically in the external
morphology of the plant.
This same process goes on in
insects and in crustaceans,
when they are infected by a
cytoplasmic bacterium called
Wolbachia.
It is in Wolbachia's interests
only to occur in females,
because they can only get into
the next generation in eggs;
they can't get into the next
generation in sperm.
And Wolbachia will feminize the
organisms that it's in,
and in some cases Wolbachia
will kill the males,
so that the male offspring
don't develop.
So these are cases where the
conflict of interest is arising
because there's selection going
on at two different levels;
on the whole organism,
and then within the cell,
on the cytoplasmic organelles.
So if we look into our own
genome--
and I'm going to spend the last
twenty minutes of this lecture
looking into our own genome--
we see a very interesting thing.
If there's potential,
through either hierarchical
selection or asymmetry of
information transmission,
to generate evolutionary
conflict, then we see that we're
not even in principle the
consistent wholes that you might
think we are.
And a very famous guy said
that, "Perhaps this is some
comfort when we face agonizing
decisions,
when we cannot make sense of
the decisions we do make,
and when the bitterness of a
civil war seems to be breaking
out in our inmost heart."
And that was Bill Hamilton,
the guy that came up with kin
selection, and wrote a lot on
evolutionary conflict.
And it's fairly poetic.
And Bill actually liked haiku a
lot.
He particularly liked Basho's
famous Narrow Road to the
Deep North,
which is--Basho was one of the
greatest Japanese haiku writers,
and was a favorite of Bill's.
So there are interesting
implications of what we're
talking about today,
and the outline basically is
going to be how you can generate
genomic conflict out of
hierarchical selection.
I'm going to make a strong
point that the opportunities for
conflict are much greater in
sexual than in asexual species.
Then I'll mention that the
uniparental transmission of
cytoplasmic genomes is probably
a method of conflict resolution.
Then I'll go on to talk about
genomic imprinting and
parent-offspring conflict in
mammals.
And then that outline there
represents what is
well-established and reliable.
When I go off this outline,
at the end, I'm going into the
speculation.
So conflict can arise in two
situations.
One is the Russian doll
situation, the babushka
situation;
multilevel hierarchical
selection.
That is when one selection
process is contained inside
another selection process;
and here you should think of
things like meiotic drive and
cancer.
The other situation is where
the transmission is
asymmetrical,
so that the different genetic
elements in the system do not
all follow the same transmission
pathways.
The cytoplasmic organelles are
the classic example.
They can only go through the
female line, they can't go
through the male line.
The nuclear genes are going
equally through both male and
female inheritance.
So there's a large and striking
difference in the way the
cytoplasmic organelles are
inherited.
So when we think about
two-level selection,
there are really two things
that can be going on.
For example,
here we have two genetic
entities contained inside a
larger thing.
Okay?
If A has a replication
advantage, at the lower level,
then it can just build up more
copies of itself,
and then when this larger thing
divides and reproduces,
it will end up in more copies,
because at this stage it was
reproducing faster.
Think petite mutation in yeast.
A petite mutation in yeast is a
mitochondrial mutation,
and basically what the petite
mutation does is it cuts out a
chunk of the DNA in the
mitochondrial genome,
so that the mitochondrial
genome can be replicated faster.
Now, of course,
if you cut out a bunch of the
mitochondrial genome,
the mitochondria aren't doing
their job of being a good energy
factory so well,
for that cell that they're
living in.
So they're gaining an
individual advantage from
mitochondria,
but they're damaging the
interests of the cell that
contains them.
And what happens is that the
ones that cut out the DNA,
that can replicate faster,
do build up a replication
advantage at the lower level.
The other possibility in
two-level selection is that
there's a segregation advantage.
There are just as many copies
made of each type,
at the lower level,
but in the process of then
forming say the gametes--
so in any replication process,
either mitotic or meiotic,
if there's a segregation
advantage,
one of them is going to get
into more copies.
So it takes the same number,
and then just in the process of
making the new cells it gains an
advantage.
And think here meiotic drive.
Okay, so that's the
paradigmatic example for
segregation advantage.
So in the petite mutation in
yeast, what's going on basically
is that there's a deletion in
the mitochondrial genome.
That allows the shorter genome
to be replicated faster.
It builds up a big population
in the cell.
However, there's a disadvantage
at the higher level,
and that is defective
metabolism.
The result is that the cell
lineage goes extinct.
And so people who work on yeast
in the lab--
if you just take a big
population of yeast and you
played it out in generation
after generation,
these petite mutations keep
popping up,
and they spread,
and then they go extinct.
They have a lower level
replication advantage,
but they have a high cost for
the cells that contain them,
and they disappear.
It's almost exactly analogous
to cancer.
In an asexual lineage,
the only kind of conflict that
is in principle possible is one
selection process contained
inside another one,
and the conflict would occur if
the lower level response differs
from the higher level response;
so if what's good at the lower
level is bad at the higher
level.
Petite mutation is a good
example.
There's no horizontal
transmission there,
because there's no sexual
reproduction going on.
So two independent lineages are
not coming into contact with
each other and mixing;
they're staying separate
through generations.
And so there isn't any way for
the lower level response to
escape the fate of the upper
level response.
So if there's a significant
conflict, a significant cost,
the lineages will die out.
So this is something that
actually can drive asexual
extinction.
In a sexual lineage,
sex is creating genetic
variation within the nuclear
genome.
It has the potential to create
genetic variation in cytoplasmic
genomes,
and it creates opportunities
for non-chromosomal genetic
elements to change hosts;
particularly interestingly in
bacteria it does this.
So some kinds of mechanisms,
that are going on during sex,
formally resemble pathogen
transmission;
the transmission of--when you
cough up a virus and it gets
into your roommate,
basically a genome is moving
horizontally from your body into
another body,
and reproducing there,
and during sex there are
opportunities for this kind of
thing to go on,
from one bacterium to another,
and certainly in organisms like
us,
from one organism to another.
So one cost of sex might be the
potential it creates for
inter-genomic conflict.
I'm not talking here directly
about sexually transmitted
diseases like gonorrhea or
syphilis.
I'm talking about the
possibility that genetic
elements infect the genomes of
other cells.
So, for example,
there could be a conflict
between bacterial plasmids and
chromosomes.
A little background on
bacterial genetics.
Bacteria usually contain
plasmids, and these things are
small circular genetic elements
and they live in the bacterial
cytoplasm.
So you can think of them as
genetic parasites.
The rest of the bacterial
genome is a large single
circular chromosome which is
attached to the cell wall of the
bacterium.
So think of the bacterium as a
balloon that has a circular
rubber band attached to the cell
wall,
but then out floating in the
balloon are these much smaller
plasmids that contain DNA and do
particular things.
The plasmids often are the
elements in the bacterium that
have genes for antibiotic
resistance,
and they can be advantageous
when antibiotics are present.
There are other plasmids that
will addict their host cells,
the bacterial cells,
to their presence by making a
poison antidote system.
Okay?
So basically what they're doing
is that they're protecting their
own cells and they are producing
chemicals that destroy cells
that don't contain the plasmids.
And this is a general principle.
If you make a long distance
poison and a short distance
antidote, you protect the
environment that you're in and
you destroy the competition.
So any bacterial cell that
doesn't inherit the antidote,
via a plasmid,
but gets the poison,
will die.
So that changes selection
dynamics, at a higher level,
and this plasmid will spread
through the population.
Very similar to that,
in some sense,
is segregation distortion.
There is a gene that was first
found in mice and--
this is important--it's just an
arbitrary accident of
developmental biology that this
segregation distorter happens to
also result in mice with short
tails.
Okay?
That's just an accident of
pleiotropy.
This gene has effects on both
segregation distortion and on
tail length, in mice.
So you can think of the fact
that it's affecting the tail as
just a marker;
it's just kind of like having a
reporter gene in there.
And we'll simplify the
situation and just consider two
alleles.
There's a t and a normal allele
that we call .
Okay, so these are the two
versions of this gene that are
sitting at the same place in the
chromosome.
If you have tt homozygotes,
they're lethal or sterile.
So if that were the only thing
that were going on,
you'd never see this thing;
it would die out real quick.
But if you have a mouse that is
heterozygous with t and ,
they produce--they're fine,
they live just fine--
and they produce 90 to 100%
t-bearing sperm.
This is again done with a long
distance poison and a short
distance antidote system.
So sitting there in the testes
of the mouse is a cell that is
making sperm,
and some of them have the t and
some of them don't,
and the sperm that have the t
in them are making poison,
which is going over and killing
the ones that don't have the t.
They're sitting spatially right
next to them in the testes,
and the sperm that have the t
are also making an antidote,
but it's only effective inside
their own sperm.
So basically what's going on is
that t's just wiping out the
competition, inside the testes,
and that ends up producing 90
to 100% t-bearing sperm.
So you have hierarchical
selection at the level of the
gamete.
You have got selection for t
and against t,
up at the level of the diploid
individuals, because up there
the tt homozygotes are lethal or
sterile.
So a 50:50 sex ratio--ignore
that, this is irrelevant right
here;
this is for,
this sentence snuck in here for
a different kind of gene action.
So this sentence is--and I
regret that, I should've edited
that out.
If the tt homozygotes didn't
die, but they suffered a
sufficiently small,
sub-lethal fitness
reduction--so if this part here
were not true--
then t would spread,
and eventually if t spreads all
the way through the population,
everybody's got the antidote,
and you don't have any
segregation distortion anymore,
and everything goes back to
normal.
If that is the case,
once t takes over the
population, there's no more
segregation distortion.
This introduces the interesting
possibility that most species
may have had a history of
segregation distortion and we
just don't notice it anymore,
because they've gone to
fixation.
In fact, we don't have any easy
method of detecting that.
We may see the traces of that,
written in the history of
things like the fairness of
meiosis,
but we can't go out right now
and easily find genetic or
biochemical evidence that we
have fossil segregation
distorters sitting in our own
genome.
It seems likely that we do,
but we don't know.
Now what about conflicts
between the nucleus and the
cytoplasm?
Well any cytoplasmic genome,
that's replicating faster,
gets a segregation advantage,
because there isn't any meiotic
mechanism that assures fair
segregation of organelles.
The chromosomes are controlled
by the spindle apparatus.
They line up at the plate,
at the middle of the cell.
They make two copies.
The spindle grabs one copy and
pulls it one way,
and the other copy and pulls it
the other.
Okay?
So that's really fair,
that's exactly 50:50.
The organelles are out there
floating around.
They're not attached to a
spindle when the cell divides,
and so basically if they can
just make more copies of
themselves,
they'll have a better chance of
getting into the dividing cells.
If you had biparental
inheritance of cytoplasmic
genomes,
that would mean that in the
same cytoplasm you would have
genetically different,
unrelated mitochondria;
genetically different,
unrelated chloroplasts.
And the consequence of that
would be conflict,
and that would be expressed as
an organelle cancer.
If you only get the cytoplasmic
genome from one parent,
then they'll very likely all be
the same genotype--
any kind of process like this
going on in the past would have
assured that there would only be
one left standing,
in that parent--and therefore
they're not in conflict with
each other.
So, in fact,
you all only contain
mitochondria from your mothers.
It's extremely rare that a
human will ever have a
mitochondrion from a father.
It does happen,
but it's a one in a billion
chance.
Okay?
So those are some of the well
established cell level scenarios
in which conflict plays out.
And before I go into the
reproductive problems in humans
that result from conflict,
I'd just like to emphasize that
this vision of evolution doesn't
sound like the beautifully
adapted world where all is for
the best,
in the best of all possible
worlds.
This is a vision of evolution
in which there is continual
conflict,
and in some cases it's never
resolved,
which means that in some cases
both sides are paying a
continual price.
So that's quite a different way
of looking at the world.
And if you're trying to derive
simplistic take-home points,
from the evolutionary view of
the human condition,
one of them would be,
as you'll see in a few minutes,
that there are probably
long-term conflicts that are
never resolved.
So reproductive problems.
In mammals there are conflicts
between mother and fetus over
how much the mother should
invest in the fetus.
The symptoms of that are
pre-eclampsia and diabetes.
There are conflicts between
mother and father over maternal
provisioning,
and those are related to
genetic imprinting of growth
genes,
and there are disturbances and
a tug-of-war balance produced by
evolutionary conflict in genes
that are expressed in the infant
brain,
and those are thought to deal
with mental illness.
This is where the line is
between well-established science
and speculation.
So the arenas in which these
things play out are in the
placenta and uterus,
and in the developing brain.
And this is the sequence of
ideas;
so I'll give you a little
intellectual history.
1961, '62, Bill Hamilton has
the idea of kin selection,
the idea that we can- a gene
can increase its fitness,
either by its actions on my own
body,
or by influencing the actions
that I take to improve the
reproductive success of
relatives in which that gene
also probably exists.
Then Bob Trivers developed
Bill's idea into
parent-offspring conflict.
And the idea of
parent-offspring conflict--which
I'll state a couple of times to
make clear--is this.
A mother is 50% related to all
of her offspring.
She is interested in making
sure that each of them has an
equal chance therefore to have
grandchildren.
Now switch your point of view
to one of the offspring.
It's 100% related to itself;
it's 50% related to a full sib;
and it's only 25% related to a
half-sib.
So from the point of view of a
gene which is sitting in our
focal offspring,
it wants to titrate its
mother's investment away from
its potential future siblings
and into itself,
until the probability of
grandchildren,
through itself,
exactly matches the probability
of grandchildren through the
others multiplied by degree of
relationship.
Okay?
It will have a full-sib if the
species is monogamous,
and it has a probability of
half-sibs if the species is
polygamous;
if the mother mates with
multiple males.
So that was Bob's insight.
Bill got the Crawford Prize,
which is the Nobel Prize in
Evolutionary Biology,
for kin selection,
and Bob got it for
parent-offspring conflict.
So those are prizes that are
worth oh six or
seven-hundred-thousand dollars,
and like Nobel Prizes,
they are awarded in Sweden,
in Stockholm.
And so these were seen as big,
important ideas.
Now David Haig then picked up
on Bob's idea,
and he said,
"Well, there's not only
conflict between parent and
offspring."
And that conflict,
by the way, is also realized
through imprinted genes in
pregnancy.
There is conflict between the
mother and the father over how
much the mother should give to
the baby, and the baby take from
the mother.
So if the father can put into
the baby a gene that then
extracts more from that mother
than the mother wants to give,
the father can gain,
to a certain point,
an advantage.
This isn't an absolute thing,
it's just saying that there is
a range of investment where it
is not advantageous for the
mother to give more to the baby,
but it is advantageous for the
father to get the mother to give
more to his baby.
Okay?
And this is mediated by genomic
imprinting.
The final step in this little
bit of intellectual history is
Bernie Crespi and Chris Badcock,
who came up with the idea that
this conflict that David Haig
identified,
which is going on during
pregnancy and is probably
mediated mostly by genes that
are having interaction in the
fetus and in the placenta,
extends into early life during
the period of suckling,
before the child is weaned,
and the conflict is then
expressed in genes that are in
the brain of the infant,
and when their tug of war,
which is in evolutionary
equilibrium,
is disrupted,
Crespi and Badcock think that
you get mental disease.
So this is Bill.
This is taken on the Amazon.
Bill died in the year 2000,
after trying to find the source
of AIDS in the Congo.
He had gone to the North Kivu
to see whether or not he could
find chimpanzees whose DNA might
match DNA in polio vaccine from
the late 1950s.
There was a hypothesis at that
time that that's how HIV got
into humans, through polio
vaccine.
It turned out to be wrong,
and Bill died just after that
trip.
This is Bob Trivers, recently.
He's a prof now at Rutgers,
and Bob had the
parent-offspring conflict
hypothesis, as a grad student at
Harvard in 1969,
'70, '71;
about there.
This is David Haig,
currently a professor at
Harvard,
and the guy who came up with
the observation that there's a
very intriguing connection
between the imprinting,
the differential imprinting of
genes in the male and the female
germ lines,
and the control of growth by
the embryo.
And this is Bernie Crespi and
Chris Badcock.
So Bernie's at Simon Fraser in
Vancouver, British Columbia,
and Chris is in London,
at the London School of
Economics.
So these are the guys who had
these ideas about evolutionary
conflict, expressed in humans.
There was a news item on the
local television station the
other night that Jacob Lykke's
research on preeclampsia had
just been published,
and it was sort of playing up
the idea that research from Yale
Medical School reveals important
pregnancy complication
consequences;
women who have preeclampsia
have worse health later in life.
That basically is a
continuation of this idea.
The OB/GYN Department at Yale
Medical School has picked up on
this stuff.
Okay, so let's run through the
logic.
The conflict between mother and
fetus over maternal provisioning
is basically this:
the fetus is selected to
extract more from the mother
than the mother is selected
provide.
It's 100% related to itself.
She's 50% related to each of
her offspring.
It wants to take more from her.
She wants to hold some back,
so she can give the same amount
to future offspring.
The way that it will do this is
by using tissue in the placenta
to secrete hormones into the
mother to manipulate her
metabolism.
It also does it,
by the way, morphologically.
It is fetal tissue in the
placenta that invades maternal
tissue,
aggressively,
and establishes tighter and
tighter connections with the
maternal blood circulation.
So if you look at the origin of
the cells in the placenta,
there's a morphological story
of conflict written there as
well.
So the symptoms experienced by
the mother are high maternal
blood pressure and
pregnancy-related diabetes,
and this will happen
particularly when this gets a
bit out of balance.
So if you're a baby,
sitting there in the womb,
and you want to get more out of
mommy, you can do two things.
You can pump up her blood
pressure so it'll force more
nutrient through the placental
barrier,
and you can play with her
metabolism so there's more sugar
in her blood.
Too much of that and the mother
gets pretty sick.
This is the arena in which it
occurs.
This is the fetal portion of
the placenta here;
you can see the invasive blood
vessels going in,
over here.
This is the maternal portion
out here, and this is where the
exchange of nutrients is
mediated.
So the evolutionary logic
behind this is that--
if we now look at the
mother-father conflict--
the father isn't going to be
related to the mother's later
offspring,
if they have other fathers.
And, by the way,
I'm now going to make a series
of statements that sound like
humans are engaged in absolutely
outrageous moral practices.
None of this logic necessarily
is going on in current
evolution,
in our current human
population, because you can
demonstrate these effects in
mice,
and we shared ancestors with
mice about sixty million years
ago.
Okay?
So a lot of the machinery
that's being detected in mice
and in sheep and in humans,
that is shared,
could very well have had to do
with the polygamy,
or lack of monogamy,
in ancestral mammals a long
time ago.
Or it could still be going on.
Now there is an asymmetry in
the male and female reproductive
possibilities.
The father's reproductive
success depends on his
successful matings.
The mother's reproductive
success depends on the number of
offspring she personally can
bear.
And if you state that brutally,
he can have several children
and other females,
while she's dealing with this
one.
So here is a Mormon polygamist.
He has two wives.
This brother is 50% related to
this sister, and 25% related to
this brother.
Okay?
So bear that scenario in mind.
That is the sort of thing which
is driving the selection
pattern.
Rare today in humans;
possibly much commoner in the
past.
What does this have to do with
imprinting, and what is
imprinting anyway?
Imprinting is a process of
methylating genes,
and if you imprint a gene,
you turn it off;
it will not be transcribed if
it's methylated.
Imprinting is used in a number
of contexts.
It's an epigenetic mechanism
that's used in development to
control cell fate.
But the kind of imprinting that
we're talking about today is a
special kind.
It's differential imprinting by
sex,
and it's not happening during
the development of the body in
order to decide whether a cell
becomes a liver cell or a brain
cell,
it's happening in the germ line
of the parents,
just before the gametes are
produced.
And the point is that the
father is imprinting certain
sets of genes and turning them
off,
and the mother is imprinting
other sets of genes and turning
them off.
Okay?
These genes that are imprinted
in the germ line are not
expressed in the fetus,
and they are then reprogrammed
in the germ line of the adult.
The adult could be either male
or female.
Right?
So when it makes its gametes,
in the next generation,
it doesn't make them with
programming the imprinting
pattern it had when it was a
baby,
it makes them with the
imprinting pattern that is
appropriate to its sex.
What's going on is this:
The father is turning off genes
that down-regulate growth in the
embryo.
The mother is turning off genes
that up-regulate growth,
and so basically--it's kind of
double negative,
because the father's turning
off stuff that acts in the
mother's interests,
and the mother's turning off
stuff that acts in the father's
interests.
But the upshot of that is that
the father is trying to program
the embryo to extract more than
the mother is prepared to give,
and the mother is resisting.
You can only see this going on
when you disturb the
equilibrium.
You can disturb the equilibrium
in a number of ways.
You can do it by genetically
transforming mice,
and the gene that you choose to
disturb the equilibrium is the
gene that does the imprinting.
Okay?
So you mutate that gene,
or you delete it,
and then you observe the
outcome.
And the effect is roughly plus
or minus 10% in birth weight.
So if the father's genes
are--if the mother's genes are
not doing their job,
so that only the father's
interests are expressed,
the embryo is about 10% heavier;
and if it's the other way
around, the embryo is about 10%
lighter.
This scenario is also supported
by the fact that if you look at
all of the genes in the body,
there are only about 100 or 200
that are imprinted.
There are very few that are
imprinted differently in the
mother and in the father,
and the ones that are imprinted
differently in the mother and
the father mostly have to do
with the control of fetal
growth.
So it's a very special set of
genes,
and they are clearly associated
with the specific function of
fetal growth,
rather with the millions of
other things that genes do in
the body.
So up to here,
you can do nice manipulation
experiments on mice,
and these have also been done
in things like sheep,
and the scenario stands.
Now, going into speculation.
The primary site is the
placenta, where there are small
deviations that can benefit
child or mother.
Large deviations are costly to
both.
So the normal situation might
be that there would be a small
deviation.
You only get a big deviation
and disease when there's a real
disruption of the imprinting
patterns and they get out of
balance;
so that if you're thinking of a
tug of war, one side falls over.
Okay?
Where are the rest of these
genes?
They're in the brain.
These are the sex
differentially imprinted genes,
the ones that are imprinted
differently in mother and
father,
and they're not controlling
fetal growth or being expressed
in the placenta,
but they are being expressed in
the brain.
And this is now Crespi and
Badcock's idea.
A deviation toward paternal
gene expression should result in
a relatively selfish offspring.
So it should be trying to take
more from the mother,
and it should be doing it now
through infant behavior rather
than through fetal physiology.
And a deviation towards
maternal gene expression should
result in an easy offspring that
would be letting the mother
relax and store up nutrition for
the next baby.
So we can't do experiments on
humans to--like we can say with
knockout genes in mice.
So what Crespi and Badcock have
done is they've looked at
neurogenomic syndromes,
single gene effects,
and idiopathic psychiatric
conditions,
to see what happens when this
tug of war in the brain is
disturbed.
Well probably the most
revealing early observation--
this was actually picked up by
David Haig,
before Bernie got into this--is
that there are imprinted genes
on chromosome 15,
that are expressed in the
brain, and if the maternal copy
is deleted or modified,
you get one syndrome,
and if the paternal copy of
this same gene is deleted,
you get another syndrome.
So Angelman syndrome is that
the maternal copy is deleted.
The paternal copy is only
imprinted in the brain;
it's not imprinted in other
parts of the body,
it's very specifically
imprinted in this tissue.
And Angelman children are
happy, retarded and
uncoordinated.
The same gene,
but with paternal copy deleted,
maternal copy imprinted,
you get, after the age of two,
you get uncontrolled eating,
hypogonadism,
delayed puberty,
and a completely different
syndrome.
Okay?
So the Angleman types,
with father's interests
over-expressed,
have prolonged suckling,
frequent crying,
hyperactive,
sleepless;
they're difficult children and
they have high rates of autism.
And the Prader-Willi children,
with maternal interest
over-expressed,
don't feed very well,
they cry weakly,
they're inactive or sleepy,
and they have high rates of
psychosis;
some kinds of psychosis are
called schizophrenia.
So what Crespi and Badcock
proposed is that if there's an
imbalance during fetal
development,
in the brain,
towards paternally expressed
imprinted genes,
you get higher birth weight,
a larger brain,
faster growth,
a cost to the mother.
The costs to the mother are
coming from selfish,
egocentric cognition and
behavior, and both mother and
child are bearing costs from any
of the negative aspects of
autistic spectrum.
Okay?
If the mother's interests are
over-expressed,
then during fetal development
you get a smaller birth weight;
you get a smaller brain,
less lateralized brain;
slower growth.
The benefits to the mother is
that the child is easier to take
care of.
There's a cost to the
offspring, it has schizophrenic
behavior.
And there's also eventually a
cost to the mother,
from the schizophrenic
behavior.
So the people who have featured
here--this is just an autistic
child sleeping on his hands.
That's Sylvia Plath,
the poet who committed suicide.
And if we look at the
correlative evidence from
idiopathic schizophrenia and
idiopathic autism--
so I think you know who those
guys are--
what you see is that associated
with schizophrenia of unknown
cause--
that's what idiopathic
means--is low birth weight;
slow growth;
small head/brain size;
better verbal;
dyslexia;
some overlap in the genes with
bipolar disorder;
major depression.
And if you look at autism,
you see that they have higher
average birth weight;
so not always higher,
but not lower.
They have faster body growth.
They tend to have large heads.
They are called hyperlexic.
They have better visual,
spatial and verbal skills,
and you can get an idiot savant
syndrome out of that.
So there is correlative
evidence.
This is not experimental,
but it is possible to go out
there in the literature and to
pull together a lot of studies
and say,
"Hey, it looks like there
are correlations with what you
might expect if this was an
over-expression of maternal
interest and this was an
over-expression of paternal
interest in the infant
brain."
Now if this connection between
evolutionary conflicts of
interests and mental disease is
ever actually established,
it's going to be one of the
most remarkable connections that
I know of.
It was completely unexpected.
Nobody ever thought that an
alternative explanation for
autism and schizophrenia would
ever come out of kin selection
and parent-offspring conflict.
Okay?
Certainly that was completely
unsuspected in the '60s,
'70s, '80s and '90s.
So I'd now like to pause and
just remind you that everything
that I've told you about a
potential connection between
evolutionary conflicts of
interest and mental disease is
speculative.
It is actually at the moment an
object of rather intense
research.
But the annals of research
journals are littered with the
corpses of beautiful ideas that
were killed by facts,
and that could very well happen
to this one.
We have to be patient and just
see what happens.
But I hope that I've been able
to communicate to you that there
is a role in science for bold
speculation,
and that it actually makes the
whole process extremely
interesting.
Now I'd like to do something
that occurred to me after I had
lunch with Bill Feldman
yesterday.
Bill's taking this course
because he's a political
scientist, and he's interested
in what evolution has to say
about politics.
So I want to give you some
take-home messages about
conflict resolution that come
out of the study of genomic
conflict.
If you want to get rid of a
conflict, make the interest of
the competing elements
symmetric.
You can do this in a host
pathogen relationship by
shifting the transmission from
horizontal to vertical.
That will reduce their
virulence.
Because, if you think about it,
then the pathogen can only get
into the next generation if its
host survives.
If it's a vertically
transmitted parasite,
that means it's transmitted
from parent to offspring.
So the parent has to survive,
to have a baby,
so that the pathogen can make
it.
So it's not in the pathogen's
interests to kill the parent.
A horizontally transmitted
pathogen, on the other hand,
can have actually quite a high
level of virulence;
and that is where all the major
diseases are,
they're all horizontally
transmitted pathogens.
And if you think about things
like Wolbachia--
remember, I was telling you
about this bacteria that
feminizes its hosts,
so that it would always be
occurring in the body of a
female.
Well there's some crustacea
that have figured out how to
solve this problem.
They take the Wolbachia and
they chop out its sex
determining gene,
and they implant the Wolbachia
sex determining gene on one of
their chromosomes,
et voilà,
there is no conflict anymore
because now the whole business
is vertically transmitted.
So they just took the offending
element,
that one offending element out
of the bacterium,
and they stuck it into their
nuclear genome,
and they created a new sex
chromosome for the crustacean.
So they also got--they made the
interest symmetric.
Both genetic elements then had
the same vertical transmission
route.
Another way that you can
resolve conflict is this.
You can suppress the meiotic
drive.
So you can punish the offenders.
And the evidence for that
basically--that there's been a
history of suppression--is the
fairness of meiosis.
You can also homogenize the
reproductive success of
competing elements within a
group, at the human level.
This can be done with monogamy.
Anything that will make
individual success depends on
group success.
So I'm going to give you a
couple of taglines to remember
this, a couple of mnemonics.
A rising tide lifts all
boats, and we're all in the same
boat.
So if you're a gene,
you should think that anything
that you can do to improve the
reproductive success of the
organism that you're sitting in,
is probably the only way you'll
improve your own,
and the fact that it's
improving everybody else's
reproductive success,
in that same genome,
is actually irrelevant to you.
You're not competing with them;
in fact, you're all
cooperating, because if you're
all in the same boat,
and you're all pulling
together, that's the only way to
get into the next generation.
And, of course,
there is this anecdote--this
isn't--we don't actually know if
this is a direct quote or not.
But it is said that as the
Declaration of Independence was
signed on July 4^(th) in
Philadelphia in 1776,
Benjamin Franklin turned to the
people who were signing it and
said,
"Gentleman,
we must indeed all hang
together or assuredly we shall
all hang separately."
So these are just mnemonics.
These are ways of remembering
the principle that the way to
suppress conflict is to generate
a situation in which everyone is
dependent upon partners for
success.
So the take-home for the
lecture basically is this.
You should think of organisms
as a hierarchy of replication
levels,
and natural selection can occur
simultaneously at all of the
levels in the organism.
This is especially important
with cytoplasmic organelles and
with meiotic drive.
Replicating units that only
occur in a few copies,
and whose replication and
segregation are strictly
controlled--
things like cell nuclei and
chromosomal genes--
do not easily cause genomic
conflict.
But if those units occur in
many copies,
and if their replication and
segregation is not strictly
controlled--
those are things like
cytoplasmic genetic elements--
they more easily cause genomic
conflict.
Conflict is much more easily
evolved and experienced in
sexual organisms than in asexual
organisms.
Okay.
