About The Prerequisite For Positive Selection
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9.6 years ago
Dejian ★ 1.3k

Is it reasonable to do positive selection among several anciently diverged species? Take insects for example. Some insects were reported to diverge around 500 million years ago. Can we get meaningful results of positive selection using this kind of data?

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What do you mean by "Is it possible to do positive selection"?

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@Niek: I have changed the word to "reasonable" to put my idea more clearly. We can always do the analysis with the data. But garbage in,garbage out. If the data is not suitable for this analysis, the result will be meaningless.

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9.6 years ago

If I understand your question, you are asking whether it is possible to detect signtures of positive selection between very divergent species, e.g. from different insect orders. The answer is no. Tests for positive selection require either intraspecific variation data (e.g. HKA test), or interspefic divergence data (e.g. Ka/Ks test) from species whose sequences are not so divegent so as to be "saturated" at silent sites (see this post). Saturation often occurs within genera or between families, and prevents any meaningful estimation of Ks. I am not aware of any results using between order sequence comparisons to identify positive selection

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Thank you, Casey. Your guess is right. That is exactly what I want to do. You have prevented me from wasting time on this fruitless work.

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Just a minor point adding to Casey's excellent answer: when divergence is high, the accuracy of alignment becomes a very serious problem. Usually, homology, a very strong statement about shared ancestry, can't be made when aligning these very divergence sequences. All these tests are meaningless if the alignment is off.

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@Casey: It seems that there are many models and tests for positive selection. Will you please recommend me some books or articles that you think are suitable for newcomers to this field? Many thanks!

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@vitis: OrthoMCL, eggNOG, and TreeFam can align sequences from very divergent species and infer gene orthology. Does that mean these orthologues can be used to do these tests?

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I agree with Casey, it doesn't make sense to do this type of tests across very large evolutionary distances. You certainly can't do the tests based on population genetic dynamics (allele frequency changes) because the OTUs in your question are too divergent, which leads to the point of Ks saturation. In fact, I wonder we'll ever see the signature of selection at molecular level on the macroevolution scale, although we know macroevolution is just a lot of steps of microevolution driven by genetic drifts and selection.

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9.6 years ago

I would strongly suggest reading Molecular Signatures of Natural Selection by Rasmus Nielsen 2005.

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+1, thanks for the article.

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Thank you for the paper.I have read it. But I am still not sure about the answer to my question. It seems to me that the paper does not mention the restriction of divergence time of species for positive analysis. One of my colleagues insists that if the species are anciently diverged they are not suitable for positive selection. I read some papers about positive selection.They usually use closely related species, e.g. human and chimpanzee. I have no strong background of computational biology. Therefore I am not sure whether the model for positive selection can handle anciently diverged species

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What tests are you interested in using?

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I was trying to detect signtures of positive selection between different insect orders. Currently I only know PAML can do positive selection. I know little about what tests can be used for this purpose. If this work is reasonable, I will go into details of positive selection; otherwise, this analysis will be aborted. Thanks.

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9.6 years ago
Ning-Yi Shao ▴ 390

I think the real stuff is the story beyond the theoretical signal. The signals are the direct clues of the selection story. But when the signal appears, we (I mean both computational biologist and wet lab biologist) should dig the story of the real world, the changing of exact environments and the changing of the species should be connected reasonably, so at least we could say our story is reasonably, not only the data analysis on the paper.

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Before telling a story, I want to make sure the methods are valid, or the story will be vulnerable. Thanks.

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