A Theory of the Evolution of Eukaryotes, Crossing Over, and Sex
James Michael Howard. (This may also be found at
http://www.naples.net/~nfn03605 with other work.)
Eukaryotic Organisms
Evolution of Eukaryotes 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 protein 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 1979, 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.
