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codon usage differences and population tests (Read 1529 times)
YER
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codon usage differences and population tests
Jul 18th, 2006 at 4:56am
 
Dear Sergei,

Hopefully you can find the time to answer this question about the selection tests applied to population samples.

Phylogeny-type tests of selection pressures typically are affected by differences in codon usage across taxa (i.e., they do not handle these difference well if they are substantial), how do you think this affects the population comparison of selection pressures across sites?

If different dN/dS patterns are present throughout the population trees and codons are used with different frequencies in the populations, then this should not seriously affect the test given that the dS and dN rates are estimated for each populations separately (and if other processes such as mutation pressures towards GC- or AT-rich genomes are neglected).

But even if mutation processes differ between populations, as long as different amino acids are selected for in the two populations (another possible consequence of codon usage bias differences), the test does not produce false positive, because it is the same type of selection pressure.

In all, I think the population test should be much more robust to differences in codon bias usage than phylogeny type of tests. Do you agree?

Thanks again, Yer
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Sergei
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Re: codon usage differences and population tests
Reply #1 - Jul 18th, 2006 at 10:16am
 
Dear Yer,

We originally designed the test for populations which are similar in codon frequency composition, but the observations you made are correct.

If you have two samples which are fairly homogeneous in codon usage WITHIN each sample, but different between the samples, then the test will correct for the difference in codon usage. Because the tests also allow synonymous rates to vary from site to site, this will correct, to an extent, for spatial mutation biases, but not entirely.

In that sense, I agree that the two-sample approach is more robust than lumping all sequences into a single phylogeny and enforcing the same codon distribution across all taxa.

There are still some limitations to keep in mind:
  • Each sample will be modeled assuming the same codon composition for all taxa
  • The substitution process is (as usual) assumed to be stationary, i.e. codon composition is not changed anywhere in the tree by the substitution process


Hope this helps,
Sergei
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