Changes

::::::::::::"The long-delayed and unique evolution of this function might indicate the involvement of some extremely rare mutation. Alternately, it may involve an ordinary mutation, but one whose physical occurrence or phenotypic expression is contingent on prior mutations in that population. We tested these hypotheses in experiments that ‘‘replayed’’ evolution from different points in that population’s history. We observed no Cit+ mutants among 8.4 x 10^12 ancestral cells, nor among 9 x 10^12 cells from 60 clones sampled in the first 15,000 generations. However, we observed a significantly greater tendency for later clones to evolve Cit+, indicating that some potentiating mutation arose by 20,000 generations. This potentiating change increased the mutation rate to Cit+ but did not cause generalized hypermutability."

::::::::::::"The long-delayed and unique evolution of this function might indicate the involvement of some extremely rare mutation. Alternately, it may involve an ordinary mutation, but one whose physical occurrence or phenotypic expression is contingent on prior mutations in that population. We tested these hypotheses in experiments that ‘‘replayed’’ evolution from different points in that population’s history. We observed no Cit+ mutants among 8.4 x 10^12 ancestral cells, nor among 9 x 10^12 cells from 60 clones sampled in the first 15,000 generations. However, we observed a significantly greater tendency for later clones to evolve Cit+, indicating that some potentiating mutation arose by 20,000 generations. This potentiating change increased the mutation rate to Cit+ but did not cause generalized hypermutability."

::::::::::::What the authors found was that the later generations really did produce more Cit+ mutants than you'd expect if the Cit+ mutation was instead randomly distributed (or, as Andy has claimed and not yets retracted, contaminated by Cit+ cells). Yes, the absolute rates didn't scale across the three difference conditions but within each experiment it is clear that the Cit+ mutants arose from cells taken at later generations. Yes, there were differences in the absolute rates under different conditions but that doesn't mean the results and conclusions about potentiated clones are wrong.

::::::::::::What the authors found was that the later generations really did produce more Cit+ mutants than you'd expect if the Cit+ mutation was instead randomly distributed (or, as Andy has claimed and not yet retracted, contaminated by Cit+ cells). Yes, the absolute rates didn't scale across the three different conditions but within each experiment it is clear that the Cit+ mutants arose from cells taken at later generations. Yes, there were differences in the absolute rates under different conditions but that doesn't mean the results and conclusions about potentiated clones are wrong.

::::::::::::As for calculations of mutation rates: Blount et al. performed additional fluctuation experiments (journal pg. 7903) in an attempt to estimate the relative effect of the potentiating mutation and calculate a rough estimate of the mutation rates. Keep in mind, those rates '''''are referenced to growth under the specific conditions used in that particular experiment''''' and were used to provide ballpark estimates for comparison to other classes of known mutations. As for the second experiment not 'scaling' (with the first?), I wouldn't expect that. The first involved clones grown in continuous liquid subcultures and both the total number of generations, cells/generation and growth conditions (e.g. liquid with nutrient replenishment vs. solid agar) are very different.--[[User:Argon|Argon]] 19:20, 17 July 2008 (EDT)

::::::::::::As for calculations of mutation rates: Blount et al. performed additional fluctuation experiments (journal pg. 7903) in an attempt to estimate the relative effect of the potentiating mutation and to calculate a rough estimate of the mutation rates. Keep in mind, those rates '''''are referenced to growth under the specific conditions used in that particular experiment''''' and were used to provide ballpark estimates for comparison to other classes of known mutations. As for the second experiment not 'scaling' (with the first?), I wouldn't expect that. The first involved clones grown in continuous liquid subcultures and both the total number of generations, cells/generation and growth conditions (e.g. liquid with nutrient replenishment vs. solid agar) are very different.--[[User:Argon|Argon]] 19:20, 17 July 2008 (EDT)

::::::::::: I have not "sidestepped" your point, Andy.  Your claim is that the number of Cit+ mutants obtained did not scale with sample size in the third experiment.  In response, I reiterated what Argon and I have said previously, specifically that there are differences between the third and second experiments that make a straight comparison between the two inappropriate.  That said, if anyone is sidestepping the issue, it is you.  Argon and I have addressed your objection previously, but your only response has been to stubbornly restate the original claim.  If you don't agree with our statements, then you must explicate why.  Additionally, I did not say or imply in any way that the third experiment was flawed.  I said that it was significantly different from the second, but this is not the same as saying it was flawed.  Argon has provided a response to the scaling of the second experiment to the first.[[User:Gerlach|Gerlach]] 20:21, 17 July 2008 (EDT)

::::::::::: I have not "sidestepped" your point, Andy.  Your claim is that the number of Cit+ mutants obtained did not scale with sample size in the third experiment.  In response, I reiterated what Argon and I have said previously, specifically that there are differences between the third and second experiments that make a straight comparison between the two inappropriate.  That said, if anyone is sidestepping the issue, it is you.  Argon and I have addressed your objection previously, but your only response has been to stubbornly restate the original claim.  If you don't agree with our statements, then you must explicate why.  Additionally, I did not say or imply in any way that the third experiment was flawed.  I said that it was significantly different from the second, but this is not the same as saying it was flawed.  Argon has provided a response to the scaling of the second experiment to the first.[[User:Gerlach|Gerlach]] 20:21, 17 July 2008 (EDT)