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Theory of Evolution of Eukaryotes, Crossing Over, and Sex

James Howard jmhoward at sprynet.com
Mon Sep 15 04:54:31 EST 1997

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 

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