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PaulK, the reason there is no rational way that feathers can evolve from scales by rmns is there are too many genetic loci which must be transformed simultaneously.

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That's an interesting assertion. Do you have any evidence for it?

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Yes, I published the mathematics which correctly describes how rmns works. Here are the links:
The basic science and mathematics of random mutation and natural selection - PubMed
The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance - PubMed
Random recombination and evolution of drug resistance - PubMed

I note that your own paper says: "Recently, it has been seen that combination therapy for the treatment of malaria has failed to prevent the emergence of drug-resistant variants."Similarly, here's a paper on the evolution of resistance to combination therapy in HIV patients.So if you propose that there was some set of natural conditions, without planning and forethought, that somehow prevented dinosaurs from evolving into birds over millions of years --- with greater efficiency that we, with intelligence, forethought, and understanding of the underlying microbiology, can prevent the evolution of drug resistance in pathogens over mere decades ... well, that's not a proposition that anyone's going to swallow without a great deal of evidence for it; it seems intrinsically unlikely.

But to judge by the abstracts of those papers there is nothing in them which relates to the number of loci which must mutate simultaneously to convert a dinosaur into a bird. We would all concede that simultaneous adaptive mutation of loci is unlikely; the question is, can you prove that such a thing would be necessary to dinosaur-bird evolution?Edited by Dr Adequate, : No reason given.

But as you correctly point out in message 76, the evolution of three things doesn't have to be like winning three lotteries; it can be like one person winning a lottery, and then one of his descendants winning a lottery, and then one of his descendants winning a lottery. I think that nature isn't actually designed to thwart evolution, and so is likely to be even less successful at doing so than things which are.To return to dinosaurs and birds, I suppose you could look at it that way and say that there were some dinosaurs that were killed or impeded in replicating for want of being able to fly. That's hardly a reason why they should not have evolved flight, is it?Edited by Dr Adequate, : No reason given.

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The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance - PubMed

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I note that your own paper says: "Recently, it has been seen that combination therapy for the treatment of malaria has failed to prevent the emergence of drug-resistant variants."

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And there is a straightforward explanation why that happens. Malaria can achieve populations of a trillion or more in an infected individual. When you have populations that large, the probabilities will become realistic that you will get members of that population with double beneficial mutations. Durable treatment for malaria will require at least three effective drugs used simultaneously. This is especially true when treating immune compromised individuals.

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Similarly, here's a paper on the evolution of resistance to combination therapy in HIV patients.

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So if you propose that there was some set of natural conditions, without planning and forethought, that somehow prevented dinosaurs from evolving into birds over millions of years --- with greater efficiency that we, with intelligence, forethought, and understanding of the underlying microbiology, can prevent the evolution of drug resistance in pathogens over mere decades ... well, that's not a proposition that anyone's going to swallow without a great deal of evidence for it; it seems intrinsically unlikely.

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What prevents reptiles (or dinosaurs if you wish) evolving into birds is the multiplication rule of probabilities. All real, measurable and repeatable examples of random mutation and natural selection verify this.

Is there some reason why the evolution of resistance in this case can't involve two or more sequential mutations? Well, the multiplication rule of probabilities would apply if, as you say, the mutations required for the evolution of birds had to happen simultaneously (or if some large number of them did). But do you have any evidence that this is the case?

It seems to me that you have only half an argument. On the one hand, you have seen the force of what Darwin said 150 years ago, that natura non facit saltus --- nature does not take leaps. So far we are in agreement. We can also agree why this is the case: because a simultaneous coordinated set of beneficial mutations is extraordinarily unlikely on statistical grounds. So far, so good.But then you add the proposition that the evolution of birds must have required such a leap. And this premise appears simply to have been plucked out of thin air.

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Doc, I never said that HIV has no possibility of evolving to 3 drug therapy. It just that the probability of someone winning three lotteries is very low, much, much lower than to two lotteries.

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But as you correctly point out in message 76, the evolution of three things doesn't have to be like winning three lotteries; it can be like one person winning a lottery, and then one of his descendants winning a lottery, and then one of his descendants winning a lottery.

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That's correct, that's the way MRSA came about. When Staph evolved resistance to penicillin, methicillin was used, when methicillin failed, the next drug was used... The use of single targeted selection pressures sequentially is the way to evolve multidrug-resistant microbes. Each step of the evolutionary process requires amplification in order to improve the probability of the next beneficial mutation occurring. When multiple selection pressures are acting simultaneously, this amplification process is disrupted. All real, measurable and repeatable examples of rmns demonstrate this.

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And selection pressures are just that, something that kills or impairs the replication of some or all members of a population. Do you think that rmns to starvation and thermal stress work differently then to targeted toxins to enzymes?

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I think that nature isn't actually designed to thwart evolution, and so is likely to be even less successful at doing so than things which are.

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I don't know what you mean by "designed". I simply tried to understand the accounting rules which govern rmns. And the importance of this is clear if you want successful and durable treatment for infectious diseases and cancers.

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To return to dinosaurs and birds, I suppose you could look at it that way and say that there were some dinosaurs that were killed or impeded in replicating for want of being able to fly. That's hardly a reason why they should not have evolved flight, is it?

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If dinosaurs wanted to fly, they will need the alleles that would enable them to do this. And there are too many genetic loci needed to be transformed for scales to become feathers by rmns. Perhaps you think there exists selection pressures which target the individual loci in a sequential manner so that scales became feathers in the same way wild variants of staphylococcus became MRSA?

But as we can see from the example of HIV and malaria, applying targeted selection pressures simultaneously also leads to the evolution of resistance. I mean simply that the combination therapies were designed, by us, to mess with the pathogens and indeed in particular to make it harder for them to evolve resistance. (And yet they still manage it!) Nature was, surely, not designed with the aim of thwarting evolution. No part of it is the result of a vast endeavor by teams of brilliant scientists determined to prevent dinosaurs from evolving flight. There are too many for them all to be transformed simultaneously, we can agree on that. If you wish to maintain that there are too many for them to have changed sequentially, over the course of millions of years, then please show your working.

This post is a response to posts 111 and 112

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And there is a straightforward explanation why that happens. Malaria can achieve populations of a trillion or more in an infected individual. When you have populations that large, the probabilities will become realistic that you will get members of that population with double beneficial mutations.

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Is there some reason why the evolution of resistance in this case can't involve two or more sequential mutations?

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Amplification requires improved fitness to reproduce. However, if the selection pressures don't drive the population to extinction, it is possible that a particular lineage which doesn't amplify but is still able to reproduce for enough generations will do enough replication trials that the necessary beneficial mutation can still occur. This is why the residual population of HIV in a well treated patient is still a danger. The vast majority of times 3 drug therapy works for HIV but the residual viral population requires monitoring for this possibility.

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What prevents reptiles (or dinosaurs if you wish) evolving into birds is the multiplication rule of probabilities.

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Well, the multiplication rule of probabilities would apply if, as you say, the mutations required for the evolution of birds had to happen simultaneously (or if some large number of them did). But do you have any evidence that this is the case?

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No, the multiplication rule applies whether the mutations occur sequentially or simultaneously. Amplification alters the value of the probabilities but the probabilities are still computed multiplicatively.

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It seems to me that you have only half an argument. On the one hand, you have seen the force of what Darwin said 150 years ago, that natura non facit saltus --- nature does not take leaps. So far we are in agreement. We can also agree why this is the case: because a simultaneous coordinated set of beneficial mutations is extraordinarily unlikely on statistical grounds. So far, so good.
But then you add the proposition that the evolution of birds must have required such a leap. And this premise appears simply to have been plucked out of thin air.

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No, what I am saying is that the creation of new alleles by rmns only works efficiently when a single gene is targeted by a single selection pressure. And that process is governed by the multiplication rule of probabilities. As soon as selection pressures target more than a single genetic locus, the process is slowed even more so because of the more complex evolutionary trajectory where the probability of each step is governed by the multiplication rule.

How then do you explain the fact that real-world evidence shows that scales or scales & feathers evolved into feathers?Models must conform to, and hopefully explain, real world evidence or they are of little value. Or, whenever the model and the evidence disagree, it is best to reexamine the model...

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That's correct, that's the way MRSA came about. When Staph evolved resistance to penicillin, methicillin was used, when methicillin failed, the next drug was used... The use of single targeted selection pressures sequentially is the way to evolve multidrug-resistant microbes.

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But as we can see from the example of HIV and malaria, applying targeted selection pressures simultaneously also leads to the evolution of resistance.

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And it takes huge populations and/or large numbers of generations in order for the probabilities to become realistic in these situations. Each time another selection pressure is added, the probabilities drop multiplicatively.

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I don't know what you mean by "designed".

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I mean simply that the combination therapies were designed, by us, to mess with the pathogens and indeed in particular to make it harder for them to evolve resistance. (And yet they still manage it!) Nature was, surely, not designed with the aim of thwarting evolution. No part of it is the result of a vast endeavor by teams of brilliant scientists determined to prevent dinosaurs from evolving flight.

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Do you think that starvation selection pressures can not occur simultaneously with thermal stress in nature. What do you think would happen to a population that was subjected to starvation selection pressure alone vs starvation selection pressure with thermal stress? What about diseases occurring during starvation and thermal stress, what about predation and starvation?...

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If dinosaurs wanted to fly, they will need the alleles that would enable them to do this. And there are too many genetic loci needed to be transformed for scales to become feathers by rmns.

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There are too many for them all to be transformed simultaneously, we can agree on that. If you wish to maintain that there are too many for them to have changed sequentially, over the course of millions of years, then please show your working.

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What I can show you is the empirical evidence of how mutation and selection works and the underlying physics and mathematical principles which govern this phenomenon. If you believe that dinosaurs can transform scales into feathers by rmns, let us know what the sequential selection pressures were and the targeted genetic loci which would do this.

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...the reason there is no rational way that feathers can evolve from scales by rmns is there are too many genetic loci which must be transformed simultaneously. Every evolutionary step (beneficial mutation) must amplify in order to improve the probability of another beneficial mutation occurring on some member of the lineage with that particular mutation. rmns only works efficiently when a single selection pressure targets a single gene at a time. As soon as selection pressures target more than a single genetic locus at a time, the multiplication rule of probabilities makes that probability much, much lower. We see this with every real, measurable and repeatable empirical example of rmns.

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How then do you explain the fact that real-world evidence shows that scales or scales & feathers evolved into feathers?

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Models must conform to, and hopefully explain, real world evidence or they are of little value. Or, whenever the model and the evidence disagree, it is best to reexamine the model...

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My model is based on real, measurable and repeatable examples of rmns. Perhaps you should reexamine your interpretation of the fossil record.

Is that a no? I presumed that by "the multiplication rule" you meant that P(A & B) = P(A) * P(B) if the events are independent. Hence for example we can use this rule to calculate the probability of me throwing six on two dice. If instead I keep rolling one die until I get a six, and then keep rolling a second die until I get a six, that's a whole different question, and the probability of me getting two sixes is in fact 1. I arrived at that result without using the multiplication rule, and indeed without using multiplication. Well, it seems to me that you also said something about birds, and I wondered if you had any evidence for it.Edited by Dr Adequate, : No reason given.

Yes, many pressures are always acting on a population. Which, of course, weakens your point. A strain of bacteria evolving resistance to just one antibiotic does so in the teeth of a thousand selection pressures. Adding the antibiotic makes it a thousand and one.And still they evolve. Well, I was already aware of that stuff. What I am unaware of is any reason why this gives us a compelling argument against the evolution of birds. I don't have a description of the sequence of mutations which produced birds, which I why I have never claimed that I did and then gone on to adduce this as a proof of the evolution of birds. You, however, seemed to be claiming that you had a proof that no such pathway exists. If you don't, then this thread is about done.