For those of you interested, we have compiled a list of objections and responses.
Here are the PS threads quoted in the article, which are now all public:
1 Like
Just looking at the parts relevant to stuff Iâve said/writtenâŚ
Section â1. Mutations & Equilibriumâ misses the point entirely. The argument I make is not about the nature of the mutations, itâs simply about the math of Sanfordâs claims. The response is all about how well that equilibrium would be past the point of extinction anyway, not all mutations are equally likely, etc.
Not relevant. The objection is that if you take Sanfordâs claims of constant fitness effects for a given mutation at face value, you eventually reach an equilibrium point. Period. If theyâre conceding that, then great.
Section â2. Natural selection equilibriumâ seems to disregard basic evolutionary dynamics, things that are definitionally true based on the meaning of words like âfitnessâ and âdeleteriousâ.
And in part 6, about the 2012 H1N1 paperâŚwow. Yeesh. Iâll just comment on the overarching methodological problem: Carter and Sanford purported to track mutation accumulation over decades, but the reference sequence they used (a 2009 pandemic H1N1 strain) was from a distinct lineage relative to the 1918 H1N1 lineage. Just two different lineages of H1N1. So tallying up the differences from 1918 to 2009âŚtheyâre not using the correct baseline reference genome. The reference they use is the result of reassortment of a non-human H1N1 lineage with human H3N2.
In other words, the reference sequence and the 1918 lineage do not share a MRCA that was H1N1. The former became H1N1 through reassortment.
Yes, mutations accumulated in the 1918 H1N1 lineage since 1918. But are they accurately characterized here? No. Itâs such a fundamental error, if this paper had been reviewed by evolutionary virologists, it would have been caught in peer review.
And thatâs putting aside all the other problems, like their claims that fitness declined without actually measuring fitness at any point.
Also, bonus points for the gratuitous potshots from Sanford and in the conclusion.
6 Likes
I read a couple of them that featured me. They were both wildly inaccurate.
@swamidass, what is the point in taking these peopleâs statements seriously?
7 Likes
What are you alleging was inaccurate? Everything was fully footnoted with word-for-word quotations.
First mention of me:
There is indeed a reference and a quotation from me. The quote is accurate and says nothing like the claim itâs attached to.
I didnât refuse to explain why nonselectable mutations should have a different spectrum of fitness effects than selectable ones. I explained it at at length. In fact, I explained it in the quotation they inaccurately applied to the previous claim.
16 Likes
There is indeed a reference and a quotation from me. The quote is accurate and says nothing like the claim itâs attached to.
⌠I was waiting for an explanation that never came. Just an assertion that it was inaccurate. This brings into view the relevance of what we said in the article:
What follows is a summary of six arguments against GE recently made at Peaceful Science , followed by our answers. The references are to forum posts (sub-posts within longer discussions). Each statement will be documented in the footnotes in case these links eventually change or disappear. A disclaimer is also appropriate: we have done our best to give accurate summaries of the intended arguments of these experts, but often we have had to piece together responses from different places, as the intended meanings were often shrouded in opaque or indirect language.
Your motto must be, âItâs hard to get refuted when nobody can figure out what youâre saying.â
Specifically, your statement,
âThe precise fitness of the genome will drift up and down very slightly, but changes are as likely to be positive as negative.â
âŚimplies equilibrium (drifting up and down). After review, I donât believe youâve been misrepresented, or at least certainly not in a big enough way to warrant any changes, in light of our disclaimer (and in light of the fact that youâre still choosing to remain opaque).
Thatâs simply false. You did assert it, but at no point have you given any explanation (even when directly asked) as to why very small changes to a machine would not adhere to the same general principle of âeasier to break than to improveâ. This was, in fact, what you acknowledged as the reason why the distribution is uneven.
You asked what was inaccurate. I told you, assuming that the only way you would fail to recognize the inaccuracy was if you hadnât read the statement and footnote. Clearly I was mistaken â and didnât notice that you were one of the people responsible. Now that Iâve gone back and re-read the claim they say I made and the quotation from me, I still have no idea why you think it might be accurate. Could you explain the connection between what I said and what you say I said?
Exactly. What it doesnât imply is that slightly deleterious mutations accumulate until their overall effect becomes large, and then that they become selectable â which is what the âclaimâ is. I said that mutations of very slight effect are never selectable and therefore beneficial and deleterious mutations are always in equilibrium, since they were never selected for in the first place. Youâre saying that they become selectable. Those are two very different idea. Are you genuinely unable to tell the difference between them?
Iâm really trying not to be rude, but before concluding that Iâm trying to be opaque, first consider the possibility that youâve overestimated your own reading comprehension.
As I said above, I provided an explanation in (among other places) the text you quoted above. If you donât understand the explanation, ask. Telling me that I havenât provided an explanation while quoting my explanation would be insulting if it werenât so ridiculous.
16 Likes
That is an egregious falsehood. I seem to recall a lengthy attempt by @glipsnort to get you to wrap your head around an analogy using printers that use toner to print pages.
6 Likes
From the article:
First, Sanford et al. are claiming that these mutations prevent reproduction. Thatâs not nearly neutral. That is strongly deleterious.
More to the point, there is evidence for an upper limit for accumulated nearly neutral deleterious mutations.
The conclusion says it all.
3 Likes
You are one of many participants here who have contributed to that particular claim, which, when taken as a whole, are represented by our synopsis. You may not have said that exact bit about âbecoming selectableâ (but you did say the other related things included there), and your exact words were noted for clarity and transparency. That means you were not misrepresented. Obviously space and time would not allow for us to write a full article responding to every statement made by every contributor in the debate, so we consolidated where possible into 6 âclassesâ of objections. We also made that clear up front.
If you want, I can look into the possibility of editing your footnote there, explaining that you only adhere to two of those three sentences in the synopsis, rather than all three.
Iâd forgotten that. Clearly, I wrote all of those posts in an attempt to be opaque.
8 Likes
That was an example of your claim about the genome being mostly junk, which is responded to in a different part of our article. Can you connect the dots for me please? What is the relevance between your claim about the genome being junk and the claim about effectively neutral mutations being even? It would seem to imply youâre saying the e. neutral mutations only happen in junk, but youâve denied that before as well.
Not a population geneticist, but doesnât this conclusion require that there be considerable variance in mutational load, at least the portion due to nearly neutral, slightly deleterious alleles among individuals? It seems to me that the GE model must assume, among other things, that there is no significant variance, and that seems like a reasonable assumption to me.
The model I have in my head is the âstraw that breaks the camelâs backâ. If what Sanford says is true then there will be a mutation that pushes the individual over the line where they can no longer reproduce. That wouldnât be a nearly neutral mutation, even if that same mutation would have been nearly neutral many generations in the past. It would seem to me that Sanfordâs own model has an upper limit on mutational load after which selection will kick in.
4 Likes
Why would you think there would be a significant variance of mutational load between individuals in the same population?
Here you go @glipsnort, hereâs an example of the âbecomes selectableâ claim that was included in our article. Feel free to explain to T_aquaticus why you disagree with this.
A mutation that causes infertility would be selectable, wouldnât it?
Of course, you would first have to demonstrate how many nearly neutral deleterious mutations would have to accumulate before there are problems. If the number is well past the point of equilibrium for back mutations and compensating mutations then the entire discussion of an upper limit is moot, at least in complex sexually reproducing eukaryotes.
That is only going to happen once the whole population has arrived at the precipice of mutational meltdown.
There is no such thing as an equilibrium point. Back mutations are a non-factor here. This is addressed in the article. Please read it.
And they wonât fall off that precipice because any additional deleterious mutations would be strongly deleterious.
Thatâs obviously false. As the number of mutations accumulates the chances of a new mutation occurring at the same base increases. If 50% of the human genome is the product of past mutations then there is a 50% chance of each new mutation occurring at a base that was previously substituted. This is why Sanford needs an estimate of how many nearly deleterious mutations it takes before there are issues.
On top of that, you also have to consider the relative effect of nearly neutral deleterious mutations and beneficial mutations. If each nearly neutral deleterious mutation causes a reduction in fitness of 1 unit but a beneficial mutation causes an increase of 50,000 units of fitness then you only need a few beneficial mutations to compensate for many nearly neutral deleterious mutations.
Epistasis is also a factor. Nearly neutral deleterious mutations can become strongly beneficial in the future due to interactions with new mutations.
2 Likes