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IFEL to identify genotypes? (Read 2197 times)
Lee Smith
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IFEL to identify genotypes?
Sep 14th, 2011 at 11:36pm
 
Hi

I'm looking at CMV immune evasion genes, some of which have been shown previously to exist as distinct genotypes within circulating viral populations. Of course, when you look at sequences of genes for which you have no phenotypic data (i.e. you have no idea what the gene does), the questions is how to identify or define a genotype? For example, a NJ tree of 34 sequences of the m04 gene from MCMV looks to me to represent 6 genotypes. But a 'lumper' may think there are only 3 genotypes from the same tree.
Looking at the same sequences using IFEL identifies 10 codons under positive selection on ancestral branches.
So, my long winded question is this: can we assume that positive selection in ancestral sequences are what results in the formation of genotypes, and therefore will an NJ tree of only those codons under positive selection give me a more definitive identification of the number of genotypes within a population?

Toughts anyone?
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Sergei
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Re: IFEL to identify genotypes?
Reply #1 - Sep 16th, 2011 at 9:55am
 
Hi Lee,

It sounds like the problem lies in the relatively loose definition of a genotype (in general for viruses). Unless the genotypes are distinct phenotypically, you are should be free to settle on whatever definition you think is reasonable. I would suggest that you simply look for monophyletic clades in genotype-determining genes using maximum likelihood trees build with PhyML, RaXmL or GARLi. You could reinforce your definition by appealing to ancestral selection, but IFEL will also take within "genotype" evolution (along internal branches) into account. You probably want to restrict your attention to deeper lineages (see Exercise on page 66 of Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login Login). Generally, building trees from sites under positive selection is frowned upon, because there is strong potential for things like convergent evolution to bias your tree.

Sergei
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