condon volatility location ----from Oxford Journals
Codon Volatility As an Indicator of Positive Selection: Data from Eukaryotic Genome Comparisons
Robert Friedman and Austin L. Hughes
Department of Biological Sciences, University of South Carolina, Columbia
Adstract:
It has been suggested that codon volatility (the proportion of the point-mutation neighbors of a codon that encode different amino acids) can be used as an index of past positive selection. We compared codon volatility with patterns of synonymous and nonsynonymous nucleotide substitution in genome-wide comparisons of orthologous genes between three pairs of related genomes: (1) the protists Plasmodium falciparum and P. yoelii, (2) the fungi Saccharomyces cerevisiae and S. paradoxus, and (3) the mammals mouse and rat. Codon volatility was not consistently associated with an elevated rate of nonsynonymous substitution, as would be expected under positive selection. Rather, the most consistent and powerful correlate of elevated codon volatility was nucleotide content at the second codon position, as expected, given the nature of the genetic code.
Which seems to conflict with your meaning, concerning what has been found.
...in the above mutation map, and unlike the pig/cow/mouse/rat mutation map, the mutations aren't predominantly at the "safer" third base of a codon, nor of a type that would be "safe".
The DNA data you are using (or posting from), is in conflict with that of Friedman & Hughes?
woops,
Abstract, not ad-stract!
...in the above mutation map, and unlike the pig/cow/mouse/rat mutation map, the mutations aren't predominantly at the "safer" third base of a codon, nor of a type that would be "safe".The DNA data you are using (or posting from), is in conflict with that of Friedman & Hughes?
No, because they're seeking to measure a different -- almost opposite -- effect from the one I was.
I was pointing out that point mutations will accumulate fastest at the third codon position, precisely because many "letter" changes at that position will be neutral (i.e. encode for the same amino acid as the unchanged codon, and thus will make no biochemical difference to the organism). In short, the third position is itself most "free" to change without affecting anything, and indeed it does change more frequently across generations than the first or second position (in codons subject to selection -- in the absence of selection, they can all change at equal rates). Or more precisely, they all change (mutate) at the same rate, but fewer changes at the first and second positions will be ultimately passed on to descendants and fix in the population, since changes there are more likely to be detrimental (as opposed to changes that are entirely neutral) and weeded out by natural selection.
The authors you cite, however, examined which of the three codon positions most *determined* how many point mutations (at any locus) were "free" to occur in a neutral manner for a *given* codon. And due to the genetic code, the answer is that the second codon position most determines whether the codon as a unit is more "locked in" or more "free to change" overall.
For example, if a codon has a "C" in the second position, if I've counted right, there are 48 different point mutations (out of 99 possible) which result in synonymous changes (that is, result in no change to the associated amino acid). But if the second position is "A", then there are only 17 different point mutations (out of 99 possible) which result in synonymous changes.
And yet in both cases, as I pointed out earlier, most of the synonymous point mutations are in the *third* codon position. In the "C" case, *all* of the 48 synonymous point mutations are in the third position -- in the "A" case, 16 out of the 17 are third-position mutations (the remaining one is a second-position mutation).