All,
Here I am to make trouble again. :)
------
This a bit long, and, I won't have time to defend it (or even explain
it), which I don't really care about doing anyway - it's just a bunch
of ruminations in a thought process that is going on along with a lot
of other things right now for me. So let it stir the pot, or not.
------
I'm just talking science right now, not theology or Biblical studies,
or even preaching (and the congregation said, "Amen to that!")
There is a form of genetic change that occurs in one step and can
cause radical effects, and needn't cause any problem for subsequent
fertility.
Some transposable elements contain powerful gene activator elements
within them. There are millions of these things in all mammalian
genomes. They make copies of themselves at essentially random places
all the time in somatic cells - it is a known mechanism for cancer
progression, either by activating a neighboring growth activating
gene or disrupting a tumor suppressor gene.
Transposition seems to be largely suppressed in the germ line cells,
but some do sneak through, and fairly regularly a transposable
element at a new position appears in a child (I'm not sure what the
current estimate is for the rate, I vaguely recall about one new one
in about every 30th kid, but I'm not at all sure.)
Mostly they are essentially neutral in effect - they land somewhere
in the genome where they have no effect, and with even a moderate
population size, most of these will be lost in a few generations due
to the random walk nature of the process. If you walk randomly near a
cliff, you are very likely to fall off before long.
A small percentage get fixed in the population by "chance," and they
accumulate over millions of years, accounting for the fact that about
45% of the human genome (and large percentages of many other genomes)
is composed of remnants of these things.
An occasional transposition will be strongly negative in effect, if,
for instance, it lands in the coding region of a single copy gene
that is dose sensitive. I spent 10 years studying the protein coded
for by a single copy tumor suppressor gene that would probably behave
that way if a transposon landed in the coding region. Germline
mutations compromising it's protein function are very rare if they
can be found at all, despite the fact that somatic mutations in the
gene occur in the majority of malignancies.
Even more rarely, a transposon will land somewhere where it causes an
effect that enhances differential reproduction. If that happens, it
is likely to be fixed in the population, or perhaps rise to an
intermediate frequency if it turns out to be harmful in the
homozygous state.
If a transposon with such an element were to insert itself in the
control region of a gene that codes for a protein or RNA that
controls the expression of many other genes, say genes expressed
specifically in certain areas of the brain, it could cause major
changes in the expression of many genes in one step.
It's quite conceivable that such a change could be necessary,
although I doubt sufficient, for expression of a moral sense. It
could, alternately, or at the same time, cause an increase in
intelligence, foresight, social intelligence, bone structure of the
head, any number of things, depending on how many and which
downstream genes are affected. In the cases that have been studied,
it is often not obvious what the common theme is for all the genes
that are controlled by a master regulator gene.
There are many precedents now for simple transpositions or
rearrangements that cause widespread changes in the expression of
many genes. A friend of mine is facing a terrible and extremely rare
cancer that is caused by a single recombination event that joins a
protein module that binds to a widely distibuted small DNA sequence
element with a very powerful gene activator domain. The result is a
powerful oncogene that ups the expression dramatically for at least
60 other genes. There are plenty of instances where a transposon or
virus insertion does the same kind of thing - activating a large
number of genes by activating an activator. A gene therapy experiment
went bad a few years ago and caused leukemia by such a mechanism.
Thus you could get a profound change in the brain and behavior and
other things very quickly.
This effect could be either dominant (so potent that it would
saturate downstream mechanisms and an additional copy would add
nothing to the effect) or co-dominant (dose dependent in its strength
- one copy has some effect, 2 copies has more) or even nearly
recessive (one copy has little or no effect, but 2 copies achieves a
threshold by activating something with strong positive cooperativity).
Since there is no chromosomal translocation involved, there are no
chromosomes being torn apart in meiosis and no problems with the
recombination events that must occur in meiosis. If the regulator
gene doesn't affect the expression of any genes involved in
fertility, there needn't be any problem with fertility, but it could
create some barrier to fertility with individuals who don't have the
transposon insertion. I think there are precedents for something like
this, but my memory is vague. I'll get to the implications of this
below.
If this big change is not to create a mixed population of descendents
of the first couple, some with extremely inferior abilities, it must
be dominant and homozygous in some mating pair or their descendents,
or it must be co-dominant and homozygous.
If it is dominant and heterozygous, some individuals will be born
without the allele and be like the earlier subspecies. If it is
codominant and heterozygous, it creates a three tiered set of
descendants (with none, 1 or 2 copies of the new allele). Here are
the all the permutations:
Homozyg Heterozyg
Dominant uniform popul 2-tiered
Co-Dominant uniform popul 3-tiered
Recessive same as what preceded 2-tiered
Homozygosity could be accomplished by "chance" (whatever that is), by
two closely related individuals who had both become homozygotes,
mating. Or it could be that one of them was homozygous and the other
heterzygous, but (by "chance") they only have homozygous children.
Or if you're not bothered by the need for consistency that someone
said is the hobgoblin of little minds (this is a private joke with
Bernie), you could have God (or a pre-incarnation of Francis Crick or
an alien or whoever appeals to you) do a cloning experiment with a
rib and duplication of Adam's X and elimination of his Y to get Eve.
(And that is why (Y) she doesn't sit around wondering why the
universe is the way it is - she just wants you to do the chores, or
dance - but I'm getting in real trouble now, so I'll stop.)
That way you get homozygosity of all loci, not just the fancy new one
with its transposon insertion. And that means nearly complete
equality (except for that boring redundancy of the X and lack of
that, oh so important, Y) so maybe I'd rather you be right about this
one, Bernie.
It's conceivable that something like all this could be behind the
shift to modern humans (Homo sapiens sapiens) from Homo erectus or
whatever came before.
Now, if the locus is to remain homozygous in the new population, or
nearly so, there must be no successful reintroduction of the old
allele to the new population. If anyone looked at the announcement of
the first draft of the Neanderthal genome the other day, it seems the
experts now think that very little distinctively Neanderthal DNA got
into our genome. David O. referred to this news account:
http://www.economist.com/science/displaystory.cfm?story_id=13139627
I will assume for the moment that this is correct. It will certainly
get modified and argued about.
(For some reasons that Neanderthal DNA in general might be strongly
selected against in the offspring of mixed matings who live among the
new men, see this:
Nasty, Brutish and Short: Neanderthals Died Young
http://blogs.sciencemag.org/newsblog/2009/02/nasty-brutish-and-short-neande.html)
This could be achieved by a barrier to fertility between the two
populations, or by co-dominant selection, or both. If the transposon
containing allele is strongly dominant, then the presence of the old
allele doesn't cause any loss of fitness except in those homozygous
for it. Thus by interbreeding with Neanderthals the old allele could
be reintroduced and rise to significant levels and carry other
Neanderthal DNA with it. However, if the new allele is co-dominant in
its phenotypic expression, heterozygotes will be at a disadvantage in
competing with homozygotes for the new allele. Combine this with some
decreased fertility of the mixed matings, and you have a pretty
strong barrier to Neanderthal DNA getting into the new population.
David is much better at this kind of reasoning than I am, and he can
shoot me down if he wants to.
For a guess at how this might work in practice, think about how a
large, very aggressive guy who had a C average in high school might
be dealt with if he somehow got into MIT. The smart little guys might
get some bruises at first, but they would win the fight in the end.
Now, what does this do to mating in the other direction? This has to
do with the striking observation that when the new men encounter the
Neanderthals in Europe in 40,000 B.P., the Neanderthals go extinct
before long. They had been fine for hundreds of thousands of years.
But encountering the new man seems to finish them off. Why?
Here's a guess. The new man likes the look of the Neanderthal's
daughter and goes over and gets her pregnant, but leaves the child,
male or female, among the Neanderthals. So you get an unusally smart
child compared to the surrounding tribe. In the first generation, the
child may be smaller than the others, but is considerably smarter and
may well live longer than his fellows. He takes a Neanderthal girl
for a mate. Over a few generations with some marrying among close
kin, you get the possibility of a homozygote for the new allele, who
has also picked up Neanderthal genes for size and strength. Now you
have something that is always awesome to behold, a very large and
strong and very smart guy. (It could work the same way, with more
emphasis on the intelligence, for a woman.)
Now that kind of person could be very good or very bad, but they are
likely to be a leader in that population, for good or ill. If Genesis
6 could be taken, among other things, as a cultural memory of
something that probably happened many times over millenia, the
effects were not usually good. An unusually smart and large man in a
society that is pretty violent to start with, becomes a "mighty man,"
a mafioso, a Nephilim, a Nimrod. He stirs up his not so smart fellows
for his own benefit, and they all go out and attack the smart little
guys from MIT, and it doesn't turn out well. The survivors, if there
are any, aren't happy and someone or some little group has to get out
of Dodge, and they "go to the East." But maybe for the Neanderthals,
the effect of the increased violence internally and externally is
eventual extinction. The new gene(s) introduced into their society
destabilizes it and it just can't recover.
Well, this set of hypotheses has grown in the telling. This all seems
plausible to me as a scientist - I'm not a specialist in human
genetics, but I have read quite a lot on the subject over the last 30
years or so, both out of personal interest and in relation to my work
first in yeast genetics and then in cancer research. (All this before
the grants dried up and I started figuring out what to do now at 57
years old.) Spinning hypotheses is the easy part.
Having said what I did above, I have to turn around and say I don't
think that that is anything like the whole story, even just
scientifically. There is at least one big weakness in what I spun
above, and I can suggest how to test it.
It seems unavoidable to me that the genetic changes necessary to make
the differences between the late hominids and us didn't occur in one
big step. There's the whole FOXP2 gene story, whatever it means. And
there are bound to be more such cases. (I haven't have time or
regular full text access to look at these things for a couple of
years.) And as far as behavior, Glenn Morton used to point out on
this group that the evidence indicates that religious behavior goes
back a long way, hundreds of thousands of years, probably.
The genetics and archeology and physical anthropology just look to be
more complicated than that.
Here's the weakness. All the population genetic evidence that I know
of (and it's not my field, so I stand to be corrected) indicates that
there never was any population bottleneck of 2 people, and certainly
not in the last 6000 or 30000 or 200,000 years.
"Mitochondrial eve" is just what David said, the last female common
ancestor of all the human mitochondrial genomes that exist today. She
may have been part of a small or a not so small population, but she
wasn't the Eve of the Bible - at least it seems very unlikely to me.
The level of genetic diversity over the whole genome, not just the
MHC, is just too high.
But that is a rather vague argument and really just the opinion of an amateur.
There is likely a much stronger argument.
David and James have argued here (if I understand them) that perhaps
the large number of alleles at many loci in the MHC that are present
in, say, chimps, could be regenerated in the descendents of Adam and
Eve. (They would have to be regenerated, because only 4 alleles per
locus could be carried through a bottleneck of 2 individuals, and
only 2 alleles if there was a cloning experiment to make Eve.) Since
there are only 4 possible bases at each position, it is suggested,
and since one might guess that specific alleles are strongly selected
for, maybe all those hundreds of alleles could be recapitulated
pretty closely in about 10^5 years starting with a set of 2 or 4 for
each locus. Maybe the selection is so powerful that a very closely
related set would emerge.
This would be a massive example of convergent evolution, but
supposedly it would be driven by selection. Modern humans do have to
deal with a set of pathogens that overlaps quite a bit with those of
other primates, and presumably that's what drives the selectable
changes at the MHC.
If this were the case, when you construct a tree using the sequence
of multiple alleles of multiple species at any locus, you should see
all the human alleles arising as a monophyletic root system coming
off someplace near the chimp allele ssequences and closely resembling
the allele set for chimps or whatever primate species where there is
a lot of data for that locus. I doubt that that is what the tree
looks like.
And even if it does, you test this by then using only the sequence at
positions that are silent - third position in some codons. And you
include a bunch of nearby positions in introns - they are very easy
to align in species as closely related as higher primates and human.
And you include any transposons and Alu sequences and small
insertions and delections that you can find that have appeared at
nearby positions within the last few million years.
I would be willing to bet that if you do that, you will not see a
monophyletic root system of human allele sequences coming off as
described above. You will see that each human allele at a particular
locus is derived most directly from that same allele in the chimp or
whatever species has had a lot of sequencing of different alleles at
the locus you are testing.
It is always possible to maintain that the positions you are testing
really aren't neutral, but if you include enough of them deep into
introns and transposable elements, it starts to look unlikely that
the majority are selected for.
And of course, you can always maintain that for some reason God just
reproduced all those mutations at the third codon position and in
introns and in all those transposon insertion sites and specific
truncations and rearrangements of the transposons that occur during
specific transposition events.
Cornelius Hunter made the argument on this list some years ago, that
all species were created separately and millions of transposon
insertions and chromosomal rearrangements were reproduced exactly and
independently to the extent that they are the same in every mammalian
species, and the pattern of those events between different species
just happened to match the phylogeny deduced by other means.
It occurred to me later that this must be the most massively
anti-parsimonious hypothesis in the history of science. William of
Ockham probably achieved something approaching infinite angular
velocity in his grave on hearing it. (The physics is wrong, but you
get the idea.)
So what do I think happened back there? I don't know. This is as far
as I've gotten with the science. Someone needs to look at loci where
there are large numbers of alleles and do something like what I
outlined above. I don't have the time or the experience with the
software or the grant money - who's going to give grant money for
something like that - the ASA? :)
I'm inclined to agree with Bernie that the science just doesn't allow
for an Adam and Eve who are the last common ancestors of all people
today. I'm inclined to agree with David that if you are willing to
balance on enough heads of logical pins that you can preserve the
possibility that they are (but modern science was the result of
losing patience with that sort thing), and I'm inclined to agree with
James (and Dante) that a moral capacity is a qualitative and defining
human gift:
Dante, The Paradiso, Canto V (Mandelbaum translation):
The greatest gift the magnanimity
of God, as He created, gave, the gift
most suited to His goodness, gift that He
most prizes, was the freedom of the will;
those beings that have intellect - all these
and none but these - received and do receive
this gift.
But now I've left the science. And I've probably achieved my latest
goal, to afflict the comfortable, comfort the afflicted, annoy the
annoying (usually me) and bless everyone, at least a little, even if
they don't know it yet.
I'm going to go and get ahold of the neck of a bottle and do the
mundane thing, drink something out of it.
Preston
To unsubscribe, send a message to majordomo@calvin.edu with
"unsubscribe asa" (no quotes) as the body of the message.
Received on Tue Feb 24 19:04:19 2009
This archive was generated by hypermail 2.1.8 : Tue Feb 24 2009 - 19:04:22 EST