Re: Conservation of information (long)
Sat, 21 Aug 1999 09:20:47 +0000

At 12:47 AM 08/21/1999 -0400, Tim Ikeda wrote:

>Reading on I find him again trying to link to selection,
>but in a different way.
> "Changing an amino acid in a protein very often affects
> the way the protein functions. An organism is generally
> well adapted to its niche**. Its proteins are well suited
> to carrying out their functions. A change in one of its
> proteins is then likely to degrade the organism in some
> way. In particular, when an organism becomes resistant to
> a drug through a change in one of its proteins, it is
> likely to become less fit in some other way. Of course,
> so long as the drug is present, the organism has to
> be resistant to survive, even at the price of being
> less fit in another way. But when the drug is removed,
> the nonresistant type is again more adaptive." pp 143-144
>** A truism. Note also that the proteins in a bacterium living in a
>broth of 25 ug/ml streptomycin without the benefit of streptomycin
>resistance are not well suited for carrying out their functions.

Tim, there is some evidence that this is not true any longer. Consider this:

beneficial mutation
"They are one of medicines biggest headaches: bacteria that have evolved
reisitance to those former wonder drugs, antibiotics. Now it appears
contrary to everyones hopes and microbiologists expectations these
troublesome microbes will remain resistant long after doctors stop
prescribing the drugs. Virginia Morell, Antibiotic Resistance: Road of No
Return, Science, 278(1997):575


"Theoretically, the genes responsible for resistance are supposed to
adversely affect the bacterias fitness. Levin explains. "You're altering a
genes normal function and therefore expect it to have a disadvantage.
But a random survey last year of Escherichia coli bacteria collected from
a day-care center in Atlanta by Levin and an Emory undergraduate, Bassam
Tomah, suggested that the theory may not hold up. In a quarter of the
bacteria sampled from the diapers of 25 infants, the researchers found
strains of E. coli still resistant to streptomycin, an antibiotic doctors
have rarely used for the last 30 years. Adding to this puzzle are bacteria
in Richard Lenskis long-term evolution study at Michigan State University
in East Lansing. These E. coli originally carried a streptomycin-resistance
gene called rps, which is known to markedly reduce the bacterias fitness.
Yet, after evolving in an antibiotic-free environment for 10 years, or
20,000 generations, Lenskis bacteria are still streptomycin-resistant. "Why
didnt that gene revert to its sensitive state, when it only required the
change of a single DNA base? askes Levin.
To find out, Levins colleauges Stephanie Schrage and veronique Perrot
allowed laboratory cutlures of E. coli with rpsL mutations to evolve in an
antibiotic-free medium for 16 days or 160 generations. They then completed
these evolved bacteria against drug-sensitive E. coli and found that they
are almost as fit."That suggests that they evovled a compensatory mutation,
says Levin, "a second genetic mutation that makes up for the loss of
fitness from the first.
Schrage and Perrot, with Levin and Nina Walker, confirmed that suspicion
by making their evolved E. coli strain drug-sensitive again. They replaced
the bacterias streptomycin-resistant rpsL gene with a sensitive version of
the gene, then set this genetically altered strain and the resistant strain
against each other ina another fitness-competition bout. The genetically
altered E. coli failed miserably implying that the compensatory mutation
reduced its fitness when not paired with the resistance gene.
The interaction between the two mutations would act as a kind of ratchet,
preventing bacteria from reverting to sensitivity. The compensatory
mutations establish an adaptive valley that virtually precludes that
population of resistant bacteria from returning to drug sensitivity,
explains Levin. And that explains why the bacteria in Lenskis lab and
possibly those in the childrens diapers have not lost their resistance.
"Those that revert, that make that one change, are at a disadvantage,
"explains Levin. The team is now trying to identify the gene tthatcarries
this compensatory mutation.
Levin suspects that the same kind of compensatory mtuations will almost
certainly be found in other resistant bacteria. But already, the findings
have clear, practical and rather frightening implications," says Marlene
Zuk, an evolutionary biologist at the University of California, Riverside.
"Its not enough to stop using antibiotics; the bacteria arent going to
revert to what they were before and antibiotics that have lost their
effectiveness wont become powerful weapons again."
~ Virginia Morell, Antibiotic Resistance: Road of No Return, Science,


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