Re: Article: Mountains of new data are challenging old views


"Robert Karl Stonjek" <rstonjek@xxxxxxxxxxxxxx> wrote:-

Genome 2.0
Mountains of new data are challenging old views
Patrick Barry
snip<
..Crick expounded what he called the "central dogma" of molecular
biology: DNA's genetic information flows strictly one way, from a gene
through a series of steps that ends in the creation of a protein.

JE:-
This is all the information that is required to refute today's Neo Darwinian
notion that selection can act empirically at the gene level of selection.
Because the arrow remains strictly one way prohibiting Lamarkian
inheritance, selection can only operate on the phenotype level and never at
the genotype level. I have been repeating this point here for about 10
years. Yet almost all Neo Darwinian models continue to assume that selection
can validly operate at the gene level. The basic, simple, biological fact
remains that not one single phenotype can validly be claimed to remain
separate in fitness to any another within the one, same Darwinian fertile
form, i.e.all the phenotypes within one fertile form have just the one, same
Darwinian fitness and have to be selected together i.e they remain 100%
fitness epistatic. Just because the genes for these phenotypes can
independently segregate at meiosis does not mean that a phenotype coded by
one of these alleles can validly be regarded within as fitness independent
which is required to allow the popular heuristic proposition that selection
operates at the gene level. Independent gene segregation does NOT allow the
inductive leap that genes remain independently fit. What this means to all
Neo Darwinian gene centric models is that alleles at minimally TWO loci and
not just the one assumed by gene centric Neo Darwinism remains MINIMALLY
VALID. IOW all gene centric models that deploy just the one locus remain
critically uncorrected because they were oversimplified. Such an uncorrected
oversimplification can allow a reversal of cause and effect within the
model. My example is Hamilton's Rule. If you correct the rule rb>c to allow
just this minimal level of gene fitness epistasis (e) it becomes (r^e) b >
c where e=2 minimally (not just 1 so it can remain deleted and forgotten).
The effect this has is to prove that MINIMALLY Hamilton's rule is out by
100%. It is not enough to sacrifice yourself to two brothers related 0.5
because 2*0.5 = 1 but to four of them because 4*(0.5^2) = 1 as a valid
MINIMAL gene fitness epistatic model.

That
principle developed into a modern orthodoxy, according to which a genome
is
a collection of discrete genes located at specific spots along a strand of
DNA. This old view got the basics right: that genes encode proteins and
that
proteins do the myriad work necessary to keep an organism alive.

JE:-
All population genetics models assume that a pattern of independent
segregation as described by the HW distribution allows the false inductive
inference that each of these genes remains empirically independently
selectable. A correct minimal model must tie any proposed empirical fitness
(no matter how fitness is defined) to TWO loci and not just the one no
matter if they independently segregate or not.

Researchers slowly realized, however, that genes occupy only about 1.5
percent of the genome. The other 98.5 percent, dubbed "junk DNA," was
regarded as useless scraps left over from billions of years of random
genetic mutations. As geneticists' knowledge progressed, this basic
picture
remained largely unquestioned. "At one time, people said, 'Why even bother
to sequence the whole genome? Why not just sequence the [protein-coding
part]?'" says Anindya Dutta, a geneticist at the University of Virginia in
Charlottesville.

JE:-
It remained unquestioned for so long because population geneticists did not
wish to correct a critical oversimplification of Darwinian evolution by
natural selection because if they did so things like Hamilton's Rule, which
remains the darling of population genetics, becomes untenable even as a
simplified model. Researcher's like Moran et al, continue to claim (like the
discredited mutationist claimed), that just a random process all-on-its-own,
which in this case is random genetic drift and not the random mutation of
the mutationist, can validly constitute evolution and not just temporal
variation reducing evolutionary theory to the _ignominious status_ of non
falsifiable. The simple fact is the people doing these things to
evolutionary theory are mathematicians and NOT scientists. Mathematics is
not a science.


Closer examination of the full human genome is now causing scientists to
return to some questions they thought they had settled. For one, they're
revisiting the very notion of what a gene is. Rather than being distinct
segments of code amid otherwise empty stretches of DNA-like houses along a
barren country road-single genes are proving to be fragmented, intertwined
with other genes, and scattered across the whole genome.

JE:-
As the deleted-from-all-population-genetics-models: gene fitness epistasis,
predicts.

Even more surprisingly, the junk DNA may not be junk after all. Most of
this
supposedly useless DNA now appears to produce transcriptions of its
genetic
code, boosting the raw information output of the genome to about 62 times
what genes alone would produce. If these active nongene regions don't
carry
code for making proteins, just what does their activity accomplish?

JE:-
Non coding DNA of the genome remains epistatic in FITNESS to the coding DNA.

"What we thought was important before was really just the tip of the
iceberg," says Hui Ge of the Whitehead Institute for Biomedical Research
in
Cambridge, Mass.
With the genome sequence in hand, exploration has moved at a brisk pace
during the past 6 years. A milestone was reached in June, when a project
called the Encyclopedia of DNA Elements (ENCODE) thoroughly mapped the
functional regions in 1 percent of the human genome. The effort involved
was
staggering: Thirty-five teams of scientists from around the world worked
for
4 years and compiled more than 600 million data points, the consortium
reported in the June 14 Nature.
From the accumulating mountains of data, scientists are building a new
picture of how the genome works as a whole. They have found mutations in
nongene regions of DNA that are linked to common diseases such as diabetes
and forms of cancer. And some researchers propose that DNA once labeled
junk
could have spawned the complex bodies of higher organisms-even the
complexities of the human brain.
SECOND FIDDLE TO A SUPERSTAR
In the emerging picture of the genome's functioning, many of the key
elements identified so far are molecules of RNA, a chemical cousin of DNA.
In the old central dogma, RNA had a strictly subservient role in the
all-important task of making proteins.

JE:-
The REVISED central dogma allows a 100% reversible relationship between DNA
<-> RNA (representing on its own, just an empty tautology).However it also
described a critical non reversible relationship between DNA <-> RNA -->
polypeptide allowing an empirically falsifiable proposition for all of
genetics to emerge from the original tautology.

An RNA molecule is made from units of
genetic code strung together, much like DNA. But while DNA has two strands
twisted together into a double helix, RNA usually has only a single
strand.

Protein synthesis begins when the two strands of a section of DNA unzip.
Units of RNA then pair up with their counterparts on one of the DNA
strands,
forming a complementary messenger RNA (mRNA) molecule. The mRNA detaches
and
floats off to other parts of the cell, where it hooks up with machinery
that
transcribes its coded message into a protein.

If RNA's only job were making proteins, then nearly all the RNAs produced
in
cells should be transcripts of protein-coding genes. (A small fraction of
RNAs serve in the protein-transcription machinery.) But in 2005, Jill
Cheng
and her colleagues at Affymetrix, a genomics company in Santa Clara,
Calif.,
showed that less than half of the RNA produced by 10 of the chromosomes in
human cells represented transcripts of traditional genes. In the team's
experiments, 57 percent of the RNA was transcribed from noncoding, "junk"
regions.

The results from ENCODE were even more striking. In the slice of DNA
studied
in that project, between 74 percent and 93 percent of the genome produced
RNA transcripts. What becomes of this tremendous output is uncertain. John
M. Greally of the Albert Einstein College of Medicine in New York says
it's
likely that some portion of it is made accidentally and simply discarded.
But the discovery that so much of the genome is being transcribed into RNA
underscores how out-of-date the central dogma has become.

JE:-
The revised central dogma is NOT "out-of date" just the continued misuse of
it within synthetic genetics based on uncorrected, simplified/oversimplified
models of Darwinian evolution by natural selection.


Indeed, the closer researchers look, the more functions they find that RNA
transcripts perform. An alphabet soup of new acronyms describes the
newfound
roles of RNAs. First there were short nuclear RNAs (snRNAs) and short
nucleolar RNAs (snoRNAs), both of which reside inside the nucleus and help
control production of other RNAs. These were joined by microRNAs (miRNAs)
and short interfering RNAs (siRNAs), which can modulate the activity of
protein-coding genes. In mice, about 34,000 of the RNA transcripts
produced
by the genome are nonprotein-coding, outnumbering the roughly 32,000
transcripts that code for proteins, according to a 2005 study by an
international group of scientists called the Functional Annotation of
Mouse
Consortium.

JE:-
The scientific method has a tried and tested way of dealing with this (if
mathematical allow it to do so). If some non coding DNA (this DNA remains
the overwheming majority of the genome) transcribe RNA's it would be
remains prudent to assume these RNA's must be doing something and _entirely
imprudent_ to assume that they do nothing. It is the mathematically based
population genetics applecart which remains the big problem; nobody wants to
upset it.

These new families of RNAs add a layer of regulation that fine-tunes the
production of proteins. While scientists already knew that some proteins
influence the activity of other genes, "there are many more RNAs than
proteins that play a regulatory role," Ge says.
Gene regulation may not sound sexy, but it's a powerful way for a cell to
evolve complex behaviors using the tools-proteins-that it already has.
Consider the difference between a one-bedroom bungalow and an ornate,
three-story McMansion.

JE:-
Yet again I call any interested reader's attention to the model proposed by
C.H. Waddington over 50 years ago which modified Haldane's basic model
(which continues to form the basis of all population genetics models) which
I posted twice to sbe. Waddington _minimally included_, i.e. did not
entirely exclude gene fitness epistasis within the HW distribution as the
new variables: developed in environment X and selected in environment X.
This seems to have been missed by everybody.

Both are made from roughly the same materials-lumber,
drywall, wiring, plumbing-and are put together with the same
tools-hammers,
saws, nails, and screws. What makes the mansion more complex is the way
that
its construction is orchestrated by rules that specify when and where each
tool and material must be used.

JE:-
All of these rules require an epistatic gene fitness. Delete this and you
delete the rules.

snip for brevity<


"The same sequences are being used for multiple functions," says Thomas R.
Gingeras of Affymetrix. That introduces complications into the evolution
of
the genome, which had until recently been assumed to act through single
DNA
mutations affecting single genes. Now, "a mutation in one of those
sequences
has to be interpreted not only in terms of [one gene], but [of] all the
other transcripts going through the region," Gingeras explains.

JE:-
In synthetic genetics, which attempts to join Mendelian analytical genetics
with Darwinian evolutionary theory, this is termed gene fitness epistasis.
It remains deleted from every population genetics model as a critical
oversimplification (no matter how you define fitness).


The implications of this single mutation-multiple consequence model are
still a matter of debate. In some cases, the RNA transcripts from DNA that
overlaps a protein-coding gene regulate that same gene, so a mutation
could
affect both the structure and the regulation of a protein. But often,
those
transcripts regulate genes that are far away, or even on different
chromosomes. This complex interweaving of genes, transcripts, and
regulation
makes the net effect of a single mutation on an organism much more
difficult
to predict, Gingeras says.
More fundamentally, it muddies scientists' conception of just what
constitutes a gene. In the established definition, a gene is a discrete
region of DNA that produces a single, identifiable protein in a cell. But
the functioning of a protein often depends on a host of RNAs that control
its activity. If a stretch of DNA known to be a protein-coding gene also
produces regulatory RNAs essential for several other genes, is it somehow
a
part of all those other genes as well?

JE:-
Welcome to the difficult empirical world of gene fitness epistasis (which
includes pleiotrophic effects of the same gene). The neat and tidy
population genetics models wrongly equated the independent segregation of
genes with independent gene fitness by allowing an independent gene centric
level of selection, which in turn, allowed Hamilton's Rule and Dawkins'
popular "selfish gene" interpretation (making Dawkins millions). However all
of this represented just a misused heuristic oversimplification of empirical
reality. The net result: the misuse of these models misrepresented
evolutionary theory to the general public. Within these uncorrected models
empirically falsifiable cause and effect was allowed to become reversed
allowing organism fitness altruism to evolve even when this remained 100%
prohibited within Darwinism as a falsification of that theory. It was
Darwinism which provided the required empirically falsifiable theory from
which all of these non refutable models remain critically oversimplified.
The absurdity of the situation: an oversimplified model of a theory was
allowed to contest and win against the very theory it was oversimplified
from. Mathematics is most certainly not a science.

snip for brevity<

Thanks Robert,

Regards,

John Edser
Independent Researcher

edser@xxxxxxxxxxxxxx

.

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