Article: Life goes on without 'vital' DNA

Robert Karl Stonjek said:

Life goes on without 'vital' DNA Sylvia Pagán
Westphal, Boston
16:30 03 June 04

It is not often that the audience at a scientific meeting
gasps in amazement during a talk. But that is what
happened recently when researchers revealed that they had
deleted huge chunks of the genome of mice without it
making any discernable difference to the animals.

The result is totally unexpected because the deleted
sequences included so-called "conserved regions" thought
to have important functions.

I didn't hear any gasps, and I was in the audience. It was
an interesting talk, however. I couldn't gather from the
presentation how robust their inference that these were
conserved regions
(i.e. what fraction were false positive), so it was a
little hard to evaluate. The speaker did mention that
many were also conserved relative to chicken, but not
to Fugu. Random possible explanations that occurred
to me (assuming the conclusion that they're conserved
is robust):
1) They are not functionally important regions conserved by
selection, but extreme cold spots of mutation.
2) They are functionally important but only in the context
of their immediately surrounding sequence, e.g. that they
easily form secondary structures that stop replication.
3) They are functionally important with modest selection
coefficients
(i.f. the study would not have been able to observe 1%
effects). This possibility would seem to require that
many conserved regions perform a single function, so
that knocking out many has the same modest effect as
knocking out one.

--
Steve Schaffner [email hidden] Immediate assurance is an
excellent sign of probable lack of insight into the topic.
Josiah Royce

"Robert Karl Stonjek" <[email hidden]> wrote in message
"]news:[email hidden]...

Quoted message said:

Life goes on without 'vital' DNA Sylvia Pagán Westphal,
Boston ... To find out the function of some of these
highly conserved non-protein-coding regions in mammals,
Edward Rubin's team at the Lawrence Berkeley National
Laboratory in California deleted two huge regions of

junk

Quoted message said:

DNA from mice containing nearly 1000 highly conserved
sequences shared between human and mice.

One of the chunks was 1.6 million DNA bases long, the
other one was over 800,000 bases long. The researchers
expected the mice to exhibit various problems as a result
of the deletions.

Yet the mice were virtually indistinguishable from normal
mice in every characteristic they measured, including
growth, metabolic functions, lifespan and overall
development. "We were quite amazed," says Rubin, who
presented the findings at a recent meeting of the Cold
Spring Harbor Laboratory in New York.

He thinks it is pretty clear that these sequences have no
major role in growth and development. "There has been a
circular argument that if it's conserved it has
activity." ...

Very interesting. These regions resist mutation, but they
don't resist wholesale deletion. Many questions. Do the
resist mutation selectively, or do they just not mutate? Are
they selfish DNA? This one bears watching. I'm curious what
happens when mice with the deletion are

ratio issues are worth noting. Or, does the deletion cause
hybrid inviability or infertility?

I wish I could see the paper. The article says "nearly 1000
highly conserved sequences shared between human and mice".
Does that mean 1000 different sequences or 1000 copies of
the same sequence? If the latter, then it is not quite so
interesting.

Gives possibly new meaning to the term "junk DNA".

Michael Ragland

Life goes on without 'vital' DNA

Group: sci.bio.evolution Date: Fri, Jun 4, 2004, 5:14pm
(EDT+4) From: [email hidden] (Robert Karl Stonjek)

Life goes on without 'vital' DNA Sylvia Pagán
Westphal, Boston
16:30 03 June 04

It is not often that the audience at a scientific meeting
gasps in amazement during a talk. But that is what happened
recently when researchers revealed that they had deleted
huge chunks of the genome of mice without it making any
discernable difference to the animals. The result is totally
unexpected because the deleted sequences included so-called
"conserved regions" thought to have important functions. All
DNA tends to acquire random mutations, but if these occur in
a region that has an important function, individuals will
not survive. Key sequences should thus remain virtually
unchanged, even between species. So by comparing the genomes
of different species and looking for regions that are
conserved, geneticists hope to pick out those that have an
important function. It was assumed that most conserved
sequences would consist of genes coding for proteins. But an
unexpected finding when the human and mouse genomes were
compared was that there are actually more conserved
sequences within the deserts of junk DNA, which does not
code for proteins. The thinking has been that these
conserved, non-coding sequences must, like genes, be there
for a reason. And indeed, one group has shown that some
conserved regions seem to affect the expression of nearby
genes. Virtually indistinguishable To find out the function
of some of these highly conserved non-protein-coding regions
in mammals, Edward Rubin's team at the Lawrence Berkeley
National Laboratory in California deleted two huge regions
of junk DNA from mice containing nearly 1000 highly
conserved sequences shared between human and mice. One of
the chunks was 1.6 million DNA bases long, the other one was
over 800,000 bases long. The researchers expected the mice
to exhibit various problems as a result of the deletions.
Yet the mice were virtually indistinguishable from normal
mice in every characteristic they measured, including
growth, metabolic functions, lifespan and overall
development. "We were quite amazed," says Rubin, who
presented the findings at a recent meeting of the Cold
Spring Harbor Laboratory in New York. He thinks it is pretty
clear that these sequences have no major role in growth and
development. "There has been a circular argument that if
it's conserved it has activity." Read the rest at New
Scientist
newscientist.comnews.jspOpen ↗
Posted by Robert Karl Stonjek

"Steve Schaffner" <[email hidden]> wrote in
message

Quoted message said:

I didn't hear any gasps, and I was in the audience.

I would have gasped, though I didn't attend.

This is exactly the sort of thing that makes science so
exciting. We think we have more or less understood how genes
relate to the phenotype, and then some totally unexpected
data comes up.

Quoted message said:

The speaker did mention that many were also conserved
relative to chicken, but not to Fugu.

Fugu (pufferfish) have an unusually small genome, which
might explain this.

Quoted message said:

Random possible explanations that occurred to me (assuming
the conclusion that they're conserved is robust):
1) They are not functionally important regions conserved
by selection, but extreme cold spots of mutation.

Don't like this one, as then you would expect a hierarchy of
perfectly conserved, slightly degraded, and severely
degraded conserved sequences.

Quoted message said:

2) They are functionally important but only in the context
of their immediately surrounding sequence, e.g. that
they easily form secondary structures that stop
replication.

So they are selfish DNA killers? This is certainly a
possibility. Another possibility is that they are the
viruses themselves, and are capable of horizontal transfer.

Quoted message said:

3) They are functionally important with modest selection
coefficients (e.g. the study would not have been able
to observe 1% effects). This possibility would seem to
require that many conserved regions perform a single
function, so that knocking out many has the same modest
effect as knocking out one.

The problem here is that we are expected to believe that the
gene has a modest selection coefficient, but changing more
than a few bases (how good is the homology?) destroys it
totally, and that the sequence has been conserved since the
mammal / bird split. I don't like that at all.

[email hidden] (Michael Ragland) wrote in message news:<[email hidden]>...

Quoted message said:

Gives possibly new meaning to the term "junk DNA".

Michael Ragland

Life goes on without 'vital' DNA

Group: sci.bio.evolution Date: Fri, Jun 4, 2004, 5:14pm
(EDT+4) From: [email hidden]
(Robert Karl Stonjek)

Life goes on without 'vital' DNA Sylvia Pagán
Westphal, Boston
16:30 03 June 04

It is not often that the audience at a scientific meeting
gasps in amazement during a talk. But that is what
happened recently when researchers revealed that they had
deleted huge chunks of the genome of mice without it
making any discernable difference to the animals. The
result is totally unexpected because the deleted
sequences included so-called "conserved regions" thought
to have important functions. All DNA tends to acquire
random mutations, but if these occur in a region that has
an important function, individuals will not survive. Key
sequences should thus remain virtually unchanged, even
between species. So by comparing the genomes of different
species and looking for regions that are conserved,
geneticists hope to pick out those that have an important
function. It was assumed that most conserved sequences
would consist of genes coding for proteins. But an
unexpected finding when the human and mouse genomes were
compared was that there are actually more conserved
sequences within the deserts of junk DNA, which does not
code for proteins. The thinking has been that these
conserved, non-coding sequences must, like genes, be
there for a reason. And indeed, one group has shown that
some conserved regions seem to affect the expression of
nearby genes.

Initially, my reaction was that this seemed like common
sence, but now that i think of it, it only seems like common
sence to me. I have long accepted the concept of DNA holding
large amounts of historic data, as well as other data. This
to me feels like common sence, only 'cause it is that
obvious feeling to me.

I have a theory called "The Theory of Reproductive
Thought", which

is actually a thinking process.

I didn't actually write a document specifically for that
theory, 'cause it seems like it is to simple and obvious for
it's own document. Rather, I included it in with Highlife
Theory. Here's the URL for Highlife Theory and the Theory of
Reproductive Thought:
conceivia.comgaia greek god.htmOpen ↗

Tony

Quoted message said:

Virtually indistinguishable To find out the function of
some of these highly conserved non-protein-coding regions
in mammals, Edward Rubin's team at the Lawrence Berkeley
National Laboratory in California deleted two huge regions
of junk DNA from mice containing nearly 1000 highly
conserved sequences shared between human and mice. One of
the chunks was 1.6 million DNA bases long, the other one
was over 800,000 bases long. The researchers expected the
mice to exhibit various problems as a result of the
deletions. Yet the mice were virtually indistinguishable
from normal mice in every characteristic they measured,
including growth, metabolic functions, lifespan and
overall development. "We were quite amazed," says Rubin,
who presented the findings at a recent meeting of the Cold
Spring Harbor Laboratory in New York. He thinks it is
pretty clear that these sequences have no major role in
growth and development. "There has been a circular
argument that if it's conserved it has activity." Read the
rest at New Scientist
newscientist.comnews.jspOpen ↗
Posted by Robert Karl Stonjek