Paul Price: What are the Substantive Critiques of Genetic Entropy?

[PDPrice (Paul Price)]

@Joe_Felsenstein

Yes, there is a disturbingly high mutation rate in humans, which would lead to a too-high mutational load. Possible explanations (a) we’ve got the mutation rate wrong, or (b) it was lower in prehistory, or © the Earth is only 6,000 years old, and The End Is Nigh, and almost all of the geology and astronomy of the last 300 years is massively wrong.

This is a rather large admission, even though it may be couched in sarcasm. Beyond question-begging, is there any evidence for A or B? Why would the mutation rate for humans go up over time (but not for animals)?

@Joe_Felsenstein

It is not established that there is a comparable problem in all, or even most, other forms of life.

Is it not true that for rather selfish reasons, humans are probably more well-studied than most other forms of life, excluding things like lab rats, fruit flies, and bacteria?

@Joe_Felsenstein

Yes, in any organism where the genome is even moderately well-adapted, more mutations (far more) will be deleterious than will be favorable. That just follows from the genome being much better than random.

If neutral theory is correct (and @glipsnort has approved of it here), why would we suspect that the genome would be much better than “random”? Neutral theory states that drift, not selection, is the main driving force of evolution.

@Joe_Felsenstein

Population genetics calculations show that natural selection can discriminate against deleterious mutations, and do so very strongly. It is telling that PDPrice does not grapple with this.

I do grapple with this. What you have just said here is in direct contradiction of neutral theory. The other population geneticist here, Dr. Schaffner, has contradicted you on this point.

@Joe_Felsenstein

As for weakly selected mutations whose selection coefficients are less than 1/(4N) in absolute value, it is very very hard to collect information on what fraction of those are deleterious.

Yes, that’s true, at least directly. However, what reason would we have not to think that the DFE for small mutations would be substantially similar to that for larger ones? As I’ve stated earlier, this is a kind of ‘beneficial mutations of the gaps’ type argument. Everything we can actually test shows a highly negative distribution. So does the general principle that “it’s easier to break a machine than to improve upon it”. This truth isn’t going to suddenly stop existing just because we’re talking about small changes rather than large ones. In fact, I think it applies even more to small changes.

@Joe_Felsenstein

On theoretical grounds, we would expect that as the genome accumulates weakly deleterious mutations, the opportunity for them to be reversed by advantageous mutations would go up (just as the accumulation of minor and not disastrous typos in a book will increase the opportunity for advantageous typos).

I responded to this here. Back mutations would only be helpful if the surrounding context was still intact. But in a case of a huge mutational load such as what you’re suggesting, this would be increasingly unlikely.

@Joe_Felsenstein

History: Motoo Kimura and Tomoko Ohta, when they put forward models of probability distributions of advantageous and deleterious mutations, were making an approximation. They were well aware that as mean fitness changed, the distributions would actually change.

To my knowledge, nobody has produced a DFE that even attempts to model beneficials alongside deleterious mutations. Beneficials are understood to be so rare as to be “outside the model”.

@Joe_Felsenstein

The 2016 Current Opinions In Pediatrics article linked to by PDPrice is oblivious to the evidence for most of the genome being junk DNA.

This is an entire other debate. I do not believe in Junk DNA and neither do an increasing segment of the secular scientific community.