How did you determine a higher bit count means the more the constraint? Be specific
Noted. Iâm not familiar with any of their stuff. I would never try to suggest that no mutations are ever beneficial, but thatâs not really the point.
I donât disagree with the quotes but I notice that you do not discuss natural selection and what happens after that is included.
Have you read Dr Sanfordâs book? I cannot recommend it highly enough; especially for one such as yourself who will have no problem understanding the nature of his arguments.
You have brought up natural selection as a solution to the problem, but that cannot be correct. We know there is a class of mutations that are too small in their effects to be selectable, and these are called âeffectively neutralâ. Kimura acknowledged that these mutations would accumulate over time and would cause a slight decline in fitness. His solution was not to invoke NS, but rather to speculate that somehow occasional mega-beneficial mutations would overpower this decline:
âUnder the present model, effectively neutral, but, in fact, very slightly deleterious mutants accumulate continuously in every speciesâŚthe rate of loss of fitness per generation may amount to 10^-7 per generation. Whether such a small rate of deterioration in fitness constitutes a threat to the survival and welfare of the species (not to the individual) is a moot point, but this will easily be taken care of by adaptive gene substitutions that must occur from time to time (say once every few hundred generations).â
Kimura, M., Model of effectively neutral mutations in which selective constraint is incorporated, Proc. Natl. Acad. Sci. USA 76(7):3440â3444, 1979.
Kimura helped to uncover the nature of the problem, but then tried to downplay it, calling it âmootâ; itâs only moot if you are simply taking Darwinian evolution as a given. Nothing about Kimuraâs model shows these âadaptive gene substitutions that must occur from time to timeâ, I wonder why? If they must occur, why not model them rather than just throwing this claim out there at the end as a rescuing device? The fact is, beneficials are so rare that they wouldnât even register on the chart. And even those we do detect are nearly always of the âreductiveâ variety. Dr Sanford responded to Kimuraâs claim further in an appendix of his book:
"In terms of a jet manual, a single misspelling might convert the command ârepeat loop 3 timesâ to ârepeat loop 33 timesâ. Or a misspelling might convert the command âattach assembly 21 into body part Aâ into âattach assembly 21 into body part Zâ. These typographical errors could result in very profound changes in the shape of the airplane â but would they ever be beneficial? If they were beneficial, could they effectively offset the loss of information arising from millions of other misspellings - degrading all the other components of the plane?â
Kimuraâs claim that âadaptive gene substitutionsâ will easily take care of this fitness decline can only make sense on a highly unrealistic view of the genome and of fitness itself. Fitness is not a substance. Itâs a stand-in word for the reality of the situation, which is the integrity of the information in the genome. As these tiny mutations are gradually garbling that information all throughout the genome over time, itâs silly to suggest that occasional âbeneficial mutationsâ would somehow undo all that damage.
Like his argument the descending ages of the Biblical patriarchs is âscientificâ evidence for GE? 
Ooooh, Creationist argument by analogy. Thatâs always a big winner in science. 
BTW, all that genetic evidence sequenced from animals back to 700,000 years is still waiting for your GE explanation. Ignoring the data still wonât make it go away.
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Bit count means constraint in this case as constraint is where the calculation comes from. The more substitutions observed the lower the bit count.
Oh, I see. That clears it up; you are definitely using a NTS fallacy. You are asserting that, by definition, if somebody is writing in favor of creation over evolution, they cannot be a âreal scientistâ (at that moment), regardless of their degrees or qualifications.
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Where did the calculation come from? Why would where a calculation comes from be a constraint? Be specific.
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This sentence does not make any sense.
If you really want to get into the mathematical details google blast bit score. You will need to invest some time to understand this. If your objective is to disqualify Gpuccioâs methods this is not going to help you.
Your answer seem evasive. Why does a higher bit count mean the more the constraint? Be specific.
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Bit count is calculated by the amount of sequence alignment. If the sequences are aligned between rats and humans for example and there is perfect alignment you then have a maximum bit score. If there is no alignment except what would be expected by chance you would have a minimum bit score.
Sequence alignment is a result of functional constraint counteracting mutation.
Yes, Kimura assumed a particular DFE of mutations. That includes the assumption that there was such a large fraction of very slightly deleterious ones that they would overpower selection. He didnât have measurements of those either. It was just a model, it had limitations and deviate from reality as models invariably always do. But you donât have any evidence that they are so prevalent that fitness decline is unavoidable. Even though such mutations are sure to exist, you donât have evidence that there are that many of them, and you donât have any evidence that they so significantly outnumber beneficial mutations that GE is unavoidable in natural populations.
Rather, what we have is actually evidence for the opposite. That they arenât that prevalent. And we know that because fitness can be measured to go up in many contexts.
That doesnât answer the question. Why does a higher bit count mean the more the constraint?
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See what I mean?
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In other words, youâre just going to assert that Kimuraâs model was wrong (even though it continues in use up until the present by modern pop gen scientists such as Eire-Walker and Keightly). Youâve made my points for me!
That is only because âfitnessâ is a word whose definition can be shifted at will in various contexts. This is a highly misleading claim. Reductive evolution is still a downward trajectory, regardless of your âfitnessâ metric chosen.
No, youâre off track. Effectively neutral mutations, by definition, are not selectable, regardless of their quantity. If they were selectable, they wouldnât be effectively neutral.
Re read what I wrote. Itsâ explained. Alignment=high bitscore=constraint. Without constraint you would not have alignment as mutations cause the sequences to go out of alignment.
Why wonât you answer the question? What is your definition of constraint? Why does a higher bit count mean the more the constraint?
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I did Tim. You need to read what I wrote and think about it.
Why canât you answer the questions Bill? What is your definition of constraint? Why does a higher bit count mean the more the constraint?
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In this case it is the resistance to amino acid sequence substitution. Is that clear?
Can you give a source for that? It sounds a lot like that FI discussion from a while back.
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Google blast bit score.