Are Mutations Random With Respect to Function?

Beg pardon? What is the evidence that this is true?

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@John_Harshman, please read the whole thread carefully before you comment. I explained already a well established point.

If you dispute this, we can take that up in a different thread.

I do dispute it. You are thinking, I believe, entirely in the context of protein-coding exons, which is a problem. And there it’s not that transitions are more likely to be beneficial, it’s that they’re less likely to be deleterious, because they are more often silent and thus often nearly neutral. Non-silent transitions are also more likely to produce a change to similar amino acids, again not so much beneficial as not deleterious. I consider that a crucial difference. Now, the genetic code may have been tuned so as to reduce damage from the more common mutations. But is that active information?

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That is precisely what I mean. There is no disagreement on the science between us.

Is that “active information”? It is by Bartlett’s definition (Jonathan Bartlett: Measuring Active Information in Biological Systems). Is that meaningful in a way relevant to ID? Not at all.

I would say that “more likely to be beneficial” doesn’t at all mean the same as “less likely to be deleterious”.

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Okay, there may be some word craft helpful there. I will think about it.

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Seems pretty straightforward to me. If the probability of beneficials is held constant, you’d just be adjusting the proportion of beneficials to neutrals. You could even imagine that increasing the probability of neutral mutations eats into both the deleterious and beneficial ones.

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Don’t we need to need to distinguish between “function” and “fitness”? And if it’s the latter concept that we care about, wouldn’t we need to examine the distribution of fitness effects (DFE) of new mutations? I’m not aware of any species in which the DFE is skewed toward beneficial mutations.

Compared to what other distribution? That’s the problem.

I’m not sure I follow. Can you elaborate?

Well, what do you mean by “skewed”? Do refer to the technical term, departure from a Gaussian distribution, symmetrical about the mean? If so, you’re comparing the observed distribution to a Gaussian distribution. @johnnyb is apparently talking about a uniform distribution, though not of fitness effects. We don’t know what distribution of fitness a uniform distribution of mutations (by site? by base composition?) would imply, but whatever that fitness distribution would be, that’s what he’s talking about.

I simply meant that I’m not aware of any species in which the proportion of new mutations that increase fitness is larger than the proportion that decrease fitness. I wasn’t intending my comment to address @johnnyb’s paper directly, moreso @swamidass’s comment quoted in the OP.

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That’s not what @swamidass meant. He meant that the proportion that increase fitness (or, really, that don’t reduce fitness) is greater than it would be in the absence of a transition bias. That is, transversions are more likely to reduce fitness than transitions, so a bias toward transitions skews the fitness distribution away from deleterious mutations. This applies pretty much only to 2-fold degenerate sites in protein-coding exons. But it’s there. Still, it hardly seems like “active information”.

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