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Author | Topic: Explaining the pro-Evolution position | |||||||||||||||||||||||||||
Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
This post is a response to posts 140, 141
quote:You can have more than one beneficial mutation for a given selection pressure, the Weinreich experiment demonstrates that. However, each particular beneficial mutation gives rise to a lineage that is on a different evolutionary trajectory than those variants with a different beneficial mutation. What each of the different variants share in common is that they must amplify (increase in number) before there is a reasonable probability of another beneficial mutation occurring on a member of that lineage. quote:What determines if a mutation is beneficial or not is whether the variant can amplify (increase in number). In a very limited sense, amplification does not have to occur to improve the probability of a beneficial mutation occurring, a small number lineage which doesn't grow in size over the generations can have enough replications (the random trial) over many generations to improve the probability of another beneficial mutation occurring on a member of that lineage.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:Thank you
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:My mathematical model predicts the behavior of every real, measurable and repeatable example of rmns. If you think I'm cherry picking the data, post a real, measurable and repeatable example of rmns that doesn't obey my mathematics.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
This post is a response to posts 146, 147, 150
quote:Taq, your analogy is not correct, with rmns, only when a member of a particular lineage gets the beneficial mutation (wins the lottery) does it improve fitness. And if there is more than a single selection pressure targeting a single gene that particular member may have to win two or more lotteries at the same time to improve fitness. Once in a while when the population is huge, that happens, like with HIV and Malaria. That's why these replicators need more than two targeted selection pressures to suppress the evolution of drug resistance quote:Here's an example: Rodenticide - Wikipedia quote:Are you suggesting that if you really shuffle a reptiles' genome you get a bird?
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:The theory of evolution doesn't explain anything. It doesn't explain how rmns works, it doesn't explain how recombination works. It's a theory which takes the concept of common descent and says every living thing we see today came from some replicator from the primordial soup. This is a belief system made up by someone who doesn't understand the consequences of the multiplication rule of probabilities. Somebody better explain correctly how rmns works if you want to understand how to prevent drug resistant microbes and failed cancer treatments.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:Ok, any mutation that is detrimental causes the loss or reduced fitness of that member. quote:Ok, but you must also assume the mice have adequate food, adequate water, no disease, no thermal stress... quote:I don't agree with your terminology or concept. Increasing food sources reduces selection pressures on populations and therefore increases the diversity of populations. Variants that would not otherwise have sufficient fitness to reproduce in the reduced food source environment would die out. While increasing the food sources will allow them to reproduce. This doesn't mean that rmns can't work in a scenario like this. A variant which can survive and reproduce on 2 of the 3 food sources could improve fitness by getting a mutation which would allow it to use the 3rd food source as well. This would be particularly important when the first two food sources disappear. quote:There is no such thing as pressures of opportunity. If a member of a population is being preyed upon, running faster, being able to jump and being able to fly can give improve fitness to reproduce. There are empirical examples of this where reptiles evolve longer legs so as to run faster and escape the predator. But this is no more an example of rmns as the evolution of Great Danes and Chihuahuas. If the reptile must evolve the alleles to escape the predator by rmns, they are dead meat. What the predator does is kill all the slower members of the population and the remaining members by recombination change the expression of existing alleles to give longer legged variants. quote:The phenotypes of populations can be altered markedly by recombination. Consider the variants seen in the canine family in just a few thousand years of selective breeding. However, the creation of new alleles by rmns is an extremely slow process, even under ideal circumstances with the correct selection pressures. And if you have multiple directional selection pressures acting simultaneously, the process only slows further. quote:Take a closer look at the Lenski starvtion selection pressure experiment, he maintains his populations at e7-e8. Yet is still takes over a thousand generations per beneficial mutation. Do you think that rmns will work more quickly if he subjects his populations to thermal stress as well as starvation stress concurrently?
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:So you have the genetic sequences for dinosaurs?
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:I had a link to a paper which is now dead given to me by Edward Max. In that link, they studied the genomes of reptiles and the genomes of birds and looked at which genes would have to be transformed to transform scales to feathers. They identified at least 8 genes which would have to be transformed. They didn't say how many mutations in each gene. quote:Last I checked, nobody has sequenced the dinosaur genome except in Jurrasic Park. quote:The equations I derived are general equations applicable to any example of rmns. They are applicable to all real, measurable and repeatable examples of rmns. If you use combination selection pressures on birds, they will not be able to evolve by rmns any differently than any other replicator. quote:Certainly, but if you are going to take a life form that can not fly and try to give that life form the alleles necessary to fly by rmns, those life forms are already the honored guests at dinner. quote:Thanks, you are correct. My point is, most real, measurable and repeatable examples of rmns are cases where there are targeted selection pressures. For example, antimicrobial resistance, herbicide resistance and so on. Have you ever seen a case where a microbe evolves resistance to iodine? It doesn't happen because iodine reacts with too many biological molecules, too many genetic loci targeted. Starvation and thermal stress target too many genetic loci simultaneously for replicators to evolve efficiently to these kinds of selection pressures. The Lenski experiments are examples of this. And when these pressures are combined, the ability to evolve to these pressures becomes multiplicatively more difficult to evolve to by rmns. quote:Fair enough, it's the directional selection pressures which I am talking about which drive rmns. quote:Again, fair enough, but I think you now recognize that single drug treatment is useless, two drug therapy works better, three drug therapy handles the vast majority of cases, four drug therapy... My paper on the evolution of drug resistance to multiple simultaneous selection pressures addresses this. There's a pattern which emerges as you add selection pressures. You are forcing lineages to do several orders of magnitude more replications for each additional selection pressure for each beneficial mutation required for adaptation. This is easy for the lineages to accomplish the amplification required when the selection pressures are applied sequentially. However, when done simultaneously, the amplification process is suppressed by the various selection pressures. quote:Fixation is a common notion taught in evolutionary biology but it is based on an incorrect understanding of the physics. Fixation is based on the notion that natural selection is a conservative phenomenon. Haldane in his substitution model is based on the assumption that the increase in one variant must be accompanied by a decrease in another variant (hence substitution). Kimura in his diffusion fixation model uses the same basic concept. In order for a variant to be fixed, the other variants must disappear. But that is not what happens with rmns. First, the probabilities of a beneficial mutation occurring are not dependent on the relative frequency of the variant but the actual number of members replicating who would benefit from the particular mutation. Second, rmns can occur with multiple different variants, each taking their own particular evolutionary trajectory to improved fitness and it doesn't matter what the other lineages are doing as long as they are not competing for the resources of the environment. None of the variants need to be fixed in order for this process to happen. Here's a video demonstrating this: Scientists create video of bacteria evolving drug resistance. I've sent an email to the people doing this experiment to try the experiment with 2 and then 3 drugs instead of the single drug experiment. Fixation is not the key variable for evolution by rmns, it is amplification to improve the probability of the next beneficial mutation.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:Doesn't matter, if the alleles don't exist in the lineage, they have to come from someplace. Modern reptiles don't have the alleles to produce feathers, where did "ancient" reptiles get the alleles?
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:No Doc, what I am saying is that rmns works the same for all replicators. rmns works in a cycle of beneficial mutation followed by amplification of that mutation to improve the probability of another beneficial mutation occurring on that lineage. quote:I have done the math and I understand that it's behind a paywall but it's there. Here's the first step in doing the math, it is determining the possible outcomes for a mutation. P(−∞ < X < +∞) = P(Ad) + P(Cy) + P(Gu) + P(Th) + P(iAd) + P(iCy) + P(iGu) + P(iTh) + P(del)+ = 1 Where the i term denotes insertion, del denotes deletion, ... denotes any other possible mutation you can think of.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:Why don't you bear us some empirical examples of your bad news?
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
The following is a response to post 182, 185
quote:Just trying to make sure I understand your scenario. quote:I guess so, ok so go on. quote:So some variant can us one food source, other variants use the second food source, and a third variant can us the remaining source? quote:You can reduce the selection pressures on a population which will allow for increasing diversity, so if you want to call that an opportunity, I guess so. quote:I've seen your math and you need to learn something about the concept of fixation, it has no bearing on rmns. quote:Is that like killing me softly with his song? You need to suggest to Lenski to run his experiment with both thermal stress and starvation stress so he doesn't have to wait a thousand generations per beneficial mutation. quote:The calculations for rmns are actually quite simple. quote:My calculations also say that if amplification doesn't occur, the probability of another beneficial mutation occurring on that lineage remains low. quote:Apparently they didn't have to escape from their predators by flying away. quote:Not bad for 20,000 generations and about 20 beneficial mutations. But considering that 30 generations of doubling should have given about e12 members with a given beneficial mutation, you have very slow amplification. Remember the uproar over Haldanes dilemma, 300 generations per evolutionary step? But Haldane's model is physically incorrect. quote:Do you think that the evolutionary trajectory is dependent on the intensity of selection? quote:You are wrong on this one Doc. Do a careful study of Haldane's and Kimura's work. It's based on the concept that an increase in one variant is linked with a decrease in the other variants. In fact Haldane's substitution model is analogus to a conservation of energy problem. Here's a link to a paper which describes this: Just a moment... Kimura's work is directly based on a diffusion equation which is also a conservative phenomenon. quote:They will be what? quote:You are wrong on this Doc. Fixation of an allele is neither necessary nor sufficient for rmns to occur. If you are so sure you are correct, explain why one variant must decrease in order for another variant to increase.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:What I mean by amplification is simply increase in number of members of a particular lineage. Replication is the principle random trial for rmns. There are two ways to increase the number of random trials, you can increase the number of members in a lineage and you can increase number generations that lineage is able to replicate. Here's an easy way to think of this. Let's say you want to know the probability of rolling at least a single 1 with the roll of 1 die 10 times or 10 dice once, or 5 dice rolled twice etc. They all give the same set of possible outcomes and probabilities. So if you have a large numbers of members in a given lineage, it doesn't take very many generations of replications to have a reasonable probability of getting that beneficial mutation. But once that beneficial mutation occurs on one of the members, it is the progenitor of a new subpopulation (lineage) which must now amplify in order to improve the probability of another beneficial mutation occuring to advance the rmns process. quote:It's the same math for all replicators.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
There has been a call to see the mathematics of rmns. So let's do it. To make it a bit clearer, we will do this mathematics in the context of a real example of rmns measured in an experiment done by Weinreich and published here: icommons.harvard.edu In this experiment, he measured the mutations which would give e coli resistance to a particular antibiotic
What Weinreich el al found was that there were a variety of variants which evolved resistance to the antibiotic. It took 5 mutations to achieve high resistance to the drug but different combinations of mutations could accomplish this. What he found was that the first beneficial mutation determined what the other required mutations would be. So for one particular variant, you can label the set of 5 mutations to give resistance A1, B1, C1, D1 and E1, for another variant, you can label the mutations A2, B2, C2, D2 and E2 and for a third variant, you can label the mutations A3, B3, C3, D3 and E3 and so on What each of the variants have in common is that the sequence of mutations for a particular variant must always give improved fitness. So here is how you would do the mathematics for the general case of a variant getting mutations A, B, C, D, and E where each additional beneficial mutation in the evolutionary trajectory gives improved fitness to reproduce against the antibiotic selection pressure. There are two random trials in this problem, the principle random trial is the replication where there are two possible outcomes, either a mutation occurs at the particular site or a mutation does not occur at the particular site. The second random trial for this problem is the mutation itself. When a mutation occurs, it may not be the beneficial mutation, it could be a detrimental or neutral mutation, neither would contribute to improved fitness of that member. So to write out the possible outcomes for a mutation at a particular site, we can use the addition rule of probabilities for mutually exclusive event. P(−∞ < X < +∞) = P(Ad) + P(Cy) + P(Gu) + P(Th) + P(iAd) + P(iCy) + P(iGu)+ P(iTh) + P(del)+ = 1 Where Ad, Cy, Gu and Th are the bases, P(Ad) would indicate the probability that Ad was substituted and so on, P(iAd) would indicate that an Ad was inserted, P(del) would indicate that the base was deleted, and ... indicates any other mutation that could possibly occur. What can be said with mathematical certainty about each of the terms in this equation, the value for each of the terms ranges between 0 and 1. One of these terms also represents the beneficial mutation. So define a term, P(BeneficialA) such that if the substitution of Ad is the beneficial mutation, P(BeneficialA) = P(Ad). If the substitution of Cy is the beneficial mutation, P(BeneficialA) = P(Cy) and so on. Now, define a term, 𝜇, the mutation rate the probability (frequency) that an error in replication will occur at a particular site in a single member in one replication. With these definitions, we can compute the probability that mutation A will occur in a single replication of some member of the population. P(A) = P(BeneficialA)𝜇 We'll stop at this point for questions, comments, complaints... Edited by Admin, : Break up the large paragraph into smaller paragraphs and add a little additional spacing.
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Kleinman Member (Idle past 364 days) Posts: 2142 From: United States Joined: |
quote:Hi, Percy, you didn't put in your post that I couldn't reply to you directly so forgive me for taking the liberty. What I'm deriving here are the general equations which govern rmns. I happen to use this bacterial example because we have empirical data. But the governing mathematics is applicable to any arbitrary example of rmns. quote:Weinreich happened to do a good job measuring the empirical data. I could have used an example of the evolution of HIV to drug therapy or the evolution of Malaria (which is haploid/diploid) which I did use for deriving the mathematics or rmns for multiple simultaneous selection pressures. quote:I'm not sure what different conclusions you mean? What I've done (and doing here) is describing the physics and mathematics of rmns. I'm just using Weinreich's paper and data as an example. So let's pick up the calculation where we have the probability of beneficial mutation A occurring in a single replication at the particular site:P(A) = P(BeneficialA)𝜇 In order to compute the probability that mutation A will occur in a population size (let's call the population size n), we first must use the complementary rule of probabilities and compute the probability that mutation A will not occur which gives the equation: P(Ac) = 1 — P(A) = 1 - P(BeneficialA)𝜇 where P(Ac) is the probability that mutation A will not occur at the particular site. Then to compute the probability that mutation A will not occur in n replications in a single generation, we use the multiplication rule of probabilities and obtain: P(Ac) = (1 — P(A))^n = (1 - P(BeneficialA)𝜇)^n Then to compute the probability that mutation A will not occur in G generations (call it nGA), we again use the multiplication rule and obtain: P(Ac) = ((1 − P(BeneficialA)𝜇)^n)^nGA = (1 − P(BeneficialA)𝜇)^n*nGA and then to compute the probability that mutation A will occur in a population size n in nGA generations, we again use the complementary rule of probabilities and obtain the following equation: P(A) = 1 − (1 − P(BeneficialA)𝜇)^(n*∗nGA) So now the mathematical question is, what is the probability that mutation B will occur on some member with mutation A. The mathematics is self evident.Again, we'll stop at this point for questions, comments, complaints...
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