Re: D. radiodurans ( was RE: BIOLOGY: Mouse and Human Genome similarity)

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Sun Dec 08 2002 - 06:23:38 MST


On Sat, 7 Dec 2002, Jeff Davis wrote:

> http://www.ornl.gov/hgmis/publicat/microbial/image3.html
>
> But the above web piece is a real eye opener. (The
> very first web site on the list when I googled D.
> radiodurans.) It gives a bit more detail than I've
> seen up till now, suggests that the genome has been
> mapped, and generally gets one jazzed about the
> possibilities.

A little known fact is that circa 1993, I made a trip
down to LLNL to their cancer/radiation biology group
and made a point of impressing on them the medical
and commercial importance of having the sequence of
D. radiodurans. I think this may have made a strong
contribution to their placing the sequencing of its
genome high on their list.

And yes, the complete genome sequence is known:
Science 286(5444):1571-1577 (1999)
ftp://ftp.tigr.org/pub/data/d_radiodurans/

This is quite significant because prior research was
having a very difficult time understanding the radiation
resistance because it was so difficult to produce mutated
organisms which lacked this property.

> I loved the graph comparing the radiation
> survivability of humans, cockroaches, E. coli, and D.
> radiodurans. At .5 kGy (whatever that means) of
> radiation, humans, roaches, and E. coli are dead.

A kGy is a "kilo-Grey" which is a measure of radiation dose.
To explain this gets into a very complicated discussion
of how radiation is absorbed by tissues. It involves
some rather complicated conversions between "rads" and "Greys".

> And what role does the 'tetrad' structure play in
> this? Might it somehow provide a fourfold redundancy
> in informational, ie DNA, backup? Some sort of
> bacterial "I'll show you mine if you show me yours"
> kind of thing.

Actually it is more complicated than this. I don't
think the redundancy is in the tetrad structure but
is instead within each cell. Most people are aren't
aware of this but the cell division time for E. coli
is ~20 minutes. But given a 4+ megabase chromosome
and the replication speed of DNA polymerase, the
chromosome cannot be copied in 20 minutes. So in
order to achieve a maximum replication potential
E. coli has to be making multiple copies of the
chromosome at the same time.

I suspect that D. radiodurans is performing similar
tricks (i.e. each cell has multiple copies of the
genome). This would allow one to sustain multiple
double strand breaks and still have valid copies
from which homologous recombination could act to
repair valid genome copies.

This is not to say that multi-cell genome exchange
(as Jeff has possibly proposed) is "impossible".
This has been suggested by scientists involved in
NASA's exploration of "nanobacteria" (i.e. no
bacteria has a "complete" genome but the "collective"
does). It solves the problem that nanobacteria
cannot hold a "complete" genome given the structural
constraints on DNA. I'm somewhat doubtful of this
solution however since it seems somewhat contrived.

But we have the genome sequence and perhaps as the
function of the proteins is determined we may indeed
discover that genome exchange is one basis for
preserving the program. Even if it hasn't been
invented by nature we could imagine its usefullness
ourselves. The problem remains however to know that
the genome being copied is a "perfect" genome.
One needs to deal with the error correction code
issue, which to my knowledge doesn't seem to be
a feature of natural genomes.

Robert



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