Variation in virus progeny

[Ulrich Melcher]

In the exchange between Marilyn Roossinck and Sue Jeffrey (see below),
Sue appears to misunderstand the distinction that, I believe, Marilyn is trying 
to make.  The distinction is between mutation rate and mutation frequency.
Quoting from Domingo and Holland (p.163 op. cit. below),
"We refer to mutation rate as the proportion of misincorporation events during 
nucleic acid synthesis, expressed as substitutions per nucleotide per round of 
template copying....
The mutation (or mutant) frequency measures the proportion of mutants (or mutant 
residues) in a population, and is expressed as substitutions per nucleotide."

The former is what Marilyn was writing about.
The latter is what Sue responded with.

Ulrich Melcher
Okla. St. Univ.

The exchange:
********************
In article <8NOV199412185336 at aardvark.ucs.uoknor.edu>,
roossinck at aardvark.ucs.uoknor.edu (ROOSSINCK,MARILYN) wrote:


> Where did you get this data that HIV generates several mutations per "genome
> replicated"??  I think you are confusing mutation rate with evolution rate, or
> the number of changes that get fixed in the genome.  I believe that by the
> current best estimates the mutation rate of HIV is about one order of 
magnitude

> lower than most RNA viruses (see Domingo and Holland's chapter in "The
> evolutionary biology of viruses" from Raven Press).  At any rate it is highly
> unlikely that influenza virus has a lower mutation rate than HIV, it just has 
a

> lower rate of mutational fixation.
> Marilyn Roossinck

I haven't done any literature research to back myself up, but having
sequenced quite a few isolates of HIV RT I can attest that the mutation
rate of HIV is indeed fairly high. On the order of two to three base
changes per thousand sequenced. Also having sequenced quite a few isolates
of flu I can attest that HIV does in fact mutate at quite a substantially
higher frequency than influenza.  This is done in cell culture isolates,
which presumably have little or no selective pressure on the virus. In
vivo, or in other systems, there can be a substantial selective pressure,
resulting in more homogeneous populations of viral progeny. 

Sue Jeffrey
Memorial Sloan-Kettering Cancer Center
New York City
email: sjeffrey at ski.mskcc.org