Cancer genomes sequenced
John Edser
to have been reposted to the group]
http://www.the-scientist.com/blog/display/56221/
"Previously, scientists studying cancer genomes had identified a handful
of so-called driver mutations -- those that have a causative effect on
the cancerous growth. But these two papers are the first to also analyze
the noncoding regions of the genome, which may also contain driver
mutations that could act by altering gene expression, Vogelstein said."
JE:-
The Neo Darwinian view that the non coding part of the genome, which
constitutes the majority of the genome, is junk, is wrong.
"Using shotgun sequencing techniques, Michael Stratton of the Wellcome
Trust Sanger Institute and the Institute of Cancer Research in the UK
and his colleagues compiled a list of more than 50,000 somatic mutations
in a small-cell lung cancer metastasis and a malignant melanoma cell
line. Comparing them to known mutations in these cancer types, the
researchers determined they had identified approximately 90% of all the
mutations in the cancer cell lines, Stratton said. Finally, using
traditional PCR techniques to search the genomes for newly identified
mutations, the shotgun sequencing appeared to result in only about a 3%
false positive rate. "That's a high quality catalog," Stratton said.
JE:-
Note that the "shotgun" approach to sequencing the genome was invented
by Craig Venter who split with Watson in an unseemly private Vs public
research battle which had to be resolved by the intervention of the then
president of the USA, Bill Clinton:
http://news.bbc.co.uk/2/hi/science/nature/716479.stm
"From these catalogs, the researchers further identified the types of
mutations that were most prominent in each cancer type and found them to
be consistent with their known causes of ultraviolet light and tobacco
carcinogens. The lung cancer genome, for example, was riddled with G to
T substitutions, while the melanoma cell line carried predominately C to
T mutations.
Gerd Pfeifer, a molecular biologist at the City of Hope clinical
research hospital in California, found the similarity among the mutation
types within a particular cancer genome "quite surprising." While
scientists had previously identified a handful of mutations found in
these particular cancer types, "people thought that was maybe a unique
situation," said Pfeifer, who was not involved in the research. "But it
seems to be a much more general phenomenon that affects the entire genome."
Thus, by knowing the complete genomes of a variety of cancer types,
Pfeifer added, "we might understand [something] about the etiology of
these cancers." For melanoma and lung cancer, scientists have a pretty
good understanding of what causes the mutations, but for many other
cancer types, such as breast or pancreatic cancer, the "mutational
signatures" revealed by these types of sequencing studies may get
scientists "closer to understanding the origin of the tumors".
JE:-
My point: these results verify that phenotypes and the genes which code
for them always were and remain to this day, DEPENDENTLY fitness SET
NESTED within organisms. IOW, organisms are nothing like the Neo
Darwinian model popularized by Dawkins et al which wrongly depicts each
organism as just a population of independent in fitness genes. Cancer
represents a typical OVER reproduction of cells (and the genes that they
contain). If somatic cells and the genes that they contains really
constituted independent units of selection then OVER reproduction of
either would not be possible simply because each and every genomic cell
and gene is now obliged to maximally reproduce itself WITHIN each
organism. The simple truth is that somatic cell reproduction represents
a MINIMAND, i.e. is always minimized so it is not a MAXIMAND. This is
because cells cannot be independently selected. The only way for
genes/cells/organs of each organism to be naturally selected is to
maximize fertile organism reproduction per population, NOT reduce it.
The correct model for gene selection is the FITNESS SET NESTED paradigm
which I have outlined here on several occasions. It presents a simple
hierarchy of 100% DEPENDENT fitnesses allowing just the ONE maximand
fitness to represent each fitness hierarchy (each fertile form) reducing
nested fitnesses to minimands for simple efficiency. The current Neo
Darwinian paradigm allows the critical organism concept to become
reduced to an independent in fitnesses population of genes which can be
naturally selected to provide organism fitness altruism, i.e. unlike the
set model, it allows a NATURALLY SELECTED REDUCTION of the the critical
Darwinian fertile organism level reproductive maximand. The Neo
Darwinian model, was and remains just an uncorrected, critical
oversimplification of the fitness set nested model.
Regards,
John Edser
Independent Researcher
William L Hunt
<ed...@ozemail.com.au> wrote:
>[This is a resend. The original was posted on 17/12/09 but appears not
>to have been reposted to the group]
>
>
>http://www.the-scientist.com/blog/display/56221/
>
>
>"Previously, scientists studying cancer genomes had identified a handful
>of so-called driver mutations -- those that have a causative effect on
>the cancerous growth. But these two papers are the first to also analyze
>the noncoding regions of the genome, which may also contain driver
>mutations that could act by altering gene expression, Vogelstein said."
>
>JE:-
>The Neo Darwinian view that the non coding part of the genome, which
>constitutes the majority of the genome, is junk, is wrong.
>
I would consider myself a Neo-Darwinian and this is not my view. I
think you would have difficulty finding anyone, Neo-Darwinian or
otherwise, that holds this view today.
The Neo-Darwinian view might be that 2% of the human genome is
functional coding, up to another 2% is composed of functional
non-coding elements, and 95% or so is composed of non-functional
sequences.
Since in humans there are about 50 point mutations per generation and
since natural selction can handle at most 2 mutations per generation,
the functional portion of the genome that natural selection maintains
must at most be 4-5% (2 divided by 50).
The extent of the functional non-coding portion is still not
determined but, speaking for myself only, I think natural selection
will probably be found to use as much of the genome as possible within
the limit imposed by the mutation rate. This means I think the
functional non-coding portion will, in time, be found to be about 2%
and roughly equal to the coding portion.
William L Hunt
.....
[snip]
.....