A Theory of the Evolution of Eukaryotes, Crossing Over and Sex
James Howard (http://www.naples.net/~nfn03605)
Steroids, histones, and mitochondria appear in relatively close
proximity in the evolution of eukaryotes. It is my theory that the
hormone, dehydroepiandrosterone (DHEA), may be the reason that
mitochondrial-like organisms (MLOs) successfully invaded "host cells,"
the combination, of which, eventually produced eukaryotic organisms.
My principal hypothesis of my theory is that DHEA is directly involved
in the opening of the DNA helix, during transcription and replication.
Based on this hypothesis, the host cell produced DHEA for
transcription and replication of its own DNA. When MLOs were included
into the milieu of the host cells, the DNA of the MLOs benefited from
the DHEA. In the following quotation, note that not only is
mitochondrial respiration stimulated by DHEA, but protrein synthesis
is also stimulated. This is an indication that DHEA positively
affects transcription of the mitochondrial DNA.
"These findings indicate that mitochondrial respiration is the
earliest factor affected by DHEA and may be associated with protein
synthesis." Journal of Nutrition 1991; 121: 240
The entry of MLO DNA into the host cell would create a competition for
DHEA between the two genomes. This would produce a selection pressure
that would affect DNA and DHEA. (Over time, I suggest, this would
stimulate an increase in endothermic organisms, as it would also
increase the numbers of mitochondria in the organisms.) My theory
suggests that DHEA exerts its effect on DNA by hydrogen bonding
between thymine and adenine bases in DNA. Therefore, the effect of
competition for DHEA in the host cell genome would be an increase in
thymine-adenine bases. An increase in T-A bases would increase the
effects of DHEA in the host genome. I suggest this is the reason that
E. coli has approximately 25% of each of the nitrogenous bases, while
humans and other mammals have about 21% cytosine and quanine and 29%
thymine and adenine. It may be that this increase in thymine and
adenine was accomplished by development of multiple sites for DNA
replication in the nuclei of eukaryotes. Replication sites should
exhibit increased areas of T-A bases. Increased replication sites
should, therefore, increase competition for DHEA by nuclear DNA.
It is known that certain levels of nuclear DNA and mitochondria must
exist before eukaryotic cells can divide. It is my theory this
occurs, because of the competition between the two DNAs for DHEA,
i.e., not enough DHEA is produced for nuclear DNA replication during
the time of mitochondrial growth, and vice versa. That is, nuclear
and mitochondrial DNA compete for a limited supply of DHEA. One waits
on the other, i.e., a time lag in mitochondrial growth and nuclear DNA
replication would develop. Eukaryotes would accommodate this lag in
DHEA availability by developing a mechanism which would inhibit
nuclear DNA replication until mitochondrial replication has finished.
Following mitochondrial use of DHEA, DHEA and mitochondrial energy
could then be used for mitosis.
I suggest the mechanisms that evolved for separating the use of DHEA,
by the two genomes, are H1 histones and the nuclear envelope,
hallmarks of the eukaryotes. H1 histones, according to my theory,
developed to repress nuclear DNA replication. That is, these histones
are a mechanism to shut down DNA opening by DHEA, therefore, freeing
up DHEA for mitochondrial use. Mitochondria do not produce histones.
Since a nuclear envelope is also characteristic of eukaryotes, the
nuclear envelope may have evolved to sequester H1 histone gene
translation in the nuclear envelope, so H1s could not turn off
mitochondrial DNA, and, therefore, mitochondrial energy. H1s are,
indeed, synthesized directly in the nuclear milieu. (In 1979, work
on H1s had established that H1s could repress transcription. Also, in
11979, I developed a detailed explanation of how the H1s can be
affected by phosphorylation and nonhistone chromosomal proteins to
open DNA for transcription. For sake of brevity, at this time, I will
post it at another time.)
Crossing Over
In 1992, I had the occasion to respond to an author of the Journal of
Reproduction and Fertility 1991; 93: 467, about the "fluctuation of
histone H1 kinase activity during meiotic maturation in porcine
oocyes." I wrote to explain how my model of transcription control by
H1s may fit their findings in meiosis. (That letter included my
mechanism of H1 control of transcription, in detail) One of my
important hypotheses, generated by my letter to them, was a new
explanation of crossing over. For this part of my theory, you need to
know that phosphorylation of H1s removes H1s from chromatin. This
phosphorylation of H1s, according to my theory, is necessary before
DNA synthesis in mitosis and meiosis. In the same manner as my
transcription theory suggests, H1s must be removed before replication
may occur. (H1 kinase phosphorlyates H1s.) Naito and Toyoda contains
a diagram of H1 kinase activity, Fig 3, page 471, that shows that H1
kinase activity is low in the germinal vesicle, rises in prometaphase
I, and reaches a maximum in metaphase I. The activity then declines
to just above that of the germinal vesicle at anaphase and telophase
I. It then increases, again, at metaphase II, essentially as high as
that of metaphase I.
As I reread some textbooks about meiosis in preparation for writing
Naito, it occurred to me that crossing over of pachytene during
meiotic prophase may result from relatively incomplete phosphorylation
of H1 histones at this time. That is, as H1 histones are removed by
phosphorylation, detached unphosphorylated H1 histones may actually
recombine with core histones of other stands of DNA and cause crossing
over. (It is established that H1s are attached at one end to the core
histones and at the other end in the "linker region of DNA" between
core histones.) During pachytene the levels of H1 kinase, according
to my theory of crossing over, is not so high; this would explain why
crossing over occurs at pachytene and not later in meiosis, when H1
kinase activity is so high. If my idea is correct, not only will this
explain crossing over, but will provide a powerful evolutionary
selection pressure for development of H1 histone formation in
evolution of eukaryotes. That is, the core histones probably evolved
first to act as support structures for DNA replication and
condensation in eukaryotes, somewhat advanced beyond yeasts. (Yeasts
do not produce H1 histones.) This extremely useful function of
crossing over would evolve along with sex and the true eukaryotes.
The idea is that if only a small fraction of H1 histones are not
phosphorylated on time, crossing over occurs. If the vast majority
are not phosphorylated, then nondisjunction occurs; the chromosomes
are literally glued together by the histones. This is a general
mechanism, supported by the following quotation.
"(1) Nondisjunction of the sex chromosomes is largely confined to the
first meiotic division; (2) nondisjunction involves chromosomes 2 and
3 as well as the sex chromosomes; this argues against a specific
geometrical problem with sex chromosomes pairing and segregation and
in favor of a more general physiological effect on the control of
meiosis; ...""Genetics 1984; 107: 609
If I am correct, this effect should be relatively global, i.e., it
should not be isolated to one particular chromosome. Also, it should
occur during the first meiotic division.
The Evolution of Sex
I suggest that protein kinase evolved to remove H1 histones totally
from DNA for replication. Since cell division would benefit from
this, it seems appropriate to assume that the activity had selection
value. That is, cells that were better at it, divided more. My
theory of the interaction of H1s and DHEA also explains
multicelluarity. That is, specialization in the manipulation of H1
removal probably occurred over time in different cells. Differential
removal of H1s could produce differences in transcription in different
cells. Eventually, the non-histone chromosomal proteins, that I
utilize to explain differential transcription, would arise.
Differential transcription, at some point, must have produced problems
for cell division, within multicellular clumps of cells. In cells in
which the chromatin exhibited very little transcription, cell division
would be a problem. I suggest the protein kinase evolved to over come
this division problem. That is, some of these cells over-expressed,
or perhaps produced a more powerful protein kinase for allowing cell
division. Since these cells would be characterized by highly
repressed DNA, the DHEA would be more readily available for the
mitochondria. This would increase the energy and cytoplasm available
for cytoplasmic division, while the nuclear DNA remained repressed.
A single event, or a single cascade of events, involving protein
kinase could have evolved that resulted in a rapid DNA replication in
cells that have increased tremendously in size, due to increased
mitochondrial function and reproduction. This scenario could
eventually produce a large cell with a haploid genome, due to a rapid
division. Since these cells would be nutrient enriched, fusion of two
of them could rapidly produce a diploid cell. This fused cell would
exhibit rapid cell divisions, because of extra mitochondrial energy
and mass. The daughter cells could produce "normal" multicellularity
as the mitochondrial and nuclear genome reestablish a normal ratio of
nuclear and mitochondrial DNA to DHEA. Eventually, the formation of
the severely repressed cells would occur, and the mechanism would
repeat itself.
All that would be necessary for "sex" to evolve are mechanisms that
would enhance the process. Such things as chromosomal part deletions,
crossing over, etc. may enhance the repression in these cells, the
size of the cytoplasm, etc. These could produce the large egg and
small sperm that we see today. Of course nature is full of the
variations leading from simple cell division, to fusion of two
similar, haploid cells, to the formation of the egg and sperm that
would increase the favorable aspect of fusion of two large haploid
cells from two different organisms.
James Howard
