Re: Conservation of information (long)

Tim Ikeda (tikeda@sprintmail.hormel.com)
Sat, 21 Aug 1999 12:22:14 -0400

My quote from Lee Spetner
>> "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.

Glenn Morton:
> Tim, there is some evidence that this is not true any longer.
> Consider this:
[examples of suppressor mutations deleted...]

Yes, & thanks for posting that example, Glenn. I think
that case was also discussed about half a year ago as a
demonstration of the evolution of an IC system.

It's important to note that populations don't stand still,
from the standpoint of biochemistry or genetics. Let's
imagine a population of bacteria started from a single
cell, and growing in liquid culture. We can also imagine
that we occassionally subculture the cells into fresh
medium to keep them "happy" and growing. Let's also assume
that a mutation leading to streptomycin resistance has
occurred in a few cells in the culture but that must don't
carry resistance to streptomycin.

At t=0, we find that the doubling time of cells in the
culture is about an hour. At t=1, we add some streptomycin
to the culture. Let's also assume that carrying the resistance
also imposes a growth rate penalty, so now these first
generation survivors can only double every 2 hours. For the
non-resistant cells, the doubling time in the presence of
streptomycin is effectively infinite (ie. they're dead) and
the culture is soon taken over by the resistant cells (now
doubling every 2 hours).

Now a 2 hour doubling time is far better than being dead, but
it's still not as fast as could be for the medium (which we
have seen is 1 hour w/o the antibiotic). Further, any
secondary mutation which increases the growth rate of a cell
will also allow cells carrying the suppressor mutation to
dominate the culture. In a culture where streptomycin
resistance is now the norm, other forms of selective pressure
may come into play (the environment has changed). Now the
pressure is not only to retain strep resistance, which every
cell now has, but also to grow faster than the other cells in
the culture. As Glenn's example provides, suppressor mutations
can arise in such instances which mitigate the effects of
the carrying the antibiotic resistance and restore growth
rates to that of the original strain.

An important thing about the bacteria carrying the double
mutations is that not only can they hold their own against
the original strain in environments w/o the antibiotic,
but they can also outcompete strains carrying the single-
antibiotic mutation in the presence of the antibiotic.
Interestingly, either mutation, by itself, appears to reduce
the growth rate of the bacteria, yet both can be established
through selection. This provides some insight into the
evolution of IC systems.

Regards,
Tim Ikeda
tikeda@sprintmail.hormel.com (despam address before use)