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Author Topic:   Rebuttal To Creationists - "Since We Can't Directly Observe Evolution..."
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 286 of 2926 (898724)
09-28-2022 3:04 PM
Reply to: Message 285 by Kleinman
09-28-2022 2:42 PM


Re: Keeps going and.going
Kleinman writes:
Pathway? What pathway? How do mutations take a pathway?
Here you go:
click here
Don't both humans and bacteria have DNA?
That doesn't answer my question.
What does the evolution of antibiotic resistance in bacteria have to do with human evolution?
On what do you base that assumption?
Your inability to address what I wrote.
So for human evolution using your equation you get:
(100,000*54.5)-54.5
Is that new math?
Yes, of the ~5 million neutral mutations that occur in that generation all but ~50 will be lost at some point after that generation. Of course, this depends on the mutation remaining neutral and not being influenced by linkage disequilibrium. At the end of the day, the equation for neutral fixation is an idealized genome and population, something akin to the ideal gas laws.

This message is a reply to:
 Message 285 by Kleinman, posted 09-28-2022 2:42 PM Kleinman has replied

Replies to this message:
 Message 287 by Kleinman, posted 09-28-2022 3:58 PM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 287 of 2926 (898731)
09-28-2022 3:58 PM
Reply to: Message 286 by Taq
09-28-2022 3:04 PM


Re: Keeps going and.going
Kleinman:
Pathway? What pathway? How do mutations take a pathway?
Taq:
Here you go:

click here

Percy says you shouldn't just post links. You need to post a quote from the link.
Kleinman:
Don't both humans and bacteria have DNA?
Taq:
That doesn't answer my question.

What does the evolution of antibiotic resistance in bacteria have to do with human evolution?

Are implying that bacteria and humans both don't have DNA?
Kleinman:
On what do you base that assumption?
Taq:
Your inability to address what I wrote.

Did you write something about how mutations take a pathway? All I saw was a link. I can post a link to a paper that shows how bacteria take a mutational pathway and it correctly predicts the behavior of the Kishony and Lenski biological evolutionary experiments. Here the link:
The basic science and mathematics of random mutation and natural selection
Here's a quote from the paper.
quote:
The mutation and natural selection phenomenon can and often does cause the failure of antimicrobial, herbicidal, pesticide and cancer treatments selection pressures. This phenomenon operates in a mathematically predictable behavior, which when understood leads to approaches to reduce and prevent the failure of the use of these selection pressures. The mathematical behavior of mutation and selection is derived using the principles given by probability theory. The derivation of the equations describing the mutation and selection phenomenon is carried out in the context of an empirical example. Copyright © 2014 John Wiley & Sons, Ltd.
Kleinman:
So for human evolution using your equation you get:
(100,000*54.5)-54.5
Is that new math?
Taq:
Yes, of the ~5 million neutral mutations that occur in that generation all but ~50 will be lost at some point after that generation. Of course, this depends on the mutation remaining neutral and not being influenced by linkage disequilibrium. At the end of the day, the equation for neutral fixation is an idealized genome and population, something akin to the ideal gas laws.

So, every member of your population gets the same 54.5 mutations every generation. Does every human on earth have the same neutral mutations as every other human?

This message is a reply to:
 Message 286 by Taq, posted 09-28-2022 3:04 PM Taq has replied

Replies to this message:
 Message 288 by Taq, posted 09-28-2022 6:07 PM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 288 of 2926 (898735)
09-28-2022 6:07 PM
Reply to: Message 287 by Kleinman
09-28-2022 3:58 PM


Re: Keeps going and.going
[qs=Kleinman] Google "evolutionary pathway". Start reading.
Are implying that bacteria and humans both don't have DNA?
What does the evolution of antibiotic resistance in bacteria have to do with human evolution?
Did you write something about how mutations take a pathway?
I wrote this:
I already explained this a previous post. Let's use an effective population size of 20,000 as described above. That would be 80,000 generations to fix a neutral allele, and at 25 years per generation that would be 2 million years. This means the earliest populations in the human lineage that had just split away from the chimp population would be fixing neutral mutation that occurred 2 million years before that. Every generation after that would be fixing neutral mutations that occurred 2 million years before them. Where is the problem?
And this:
Given your lack of response, are you tacitly agreeing that we should see fixation of neutral mutations in each generation?

Or are you still so confused that you think only 1 mutation can move towards fixation at a time, and that all other neutral mutations can not begin to move towards fixation until that 1 neutral mutation is fixed?
So, every member of your population gets the same 54.5 mutations every generation.
That's what fixation means.
Does every human on earth have the same neutral mutations as every other human?
No, they don't. As already described, neutral mutations occur at different points in the past so they are all at different points in their journey towards either being lost or becoming fixed.

This message is a reply to:
 Message 287 by Kleinman, posted 09-28-2022 3:58 PM Kleinman has replied

Replies to this message:
 Message 289 by Kleinman, posted 09-28-2022 7:53 PM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 289 of 2926 (898737)
09-28-2022 7:53 PM
Reply to: Message 288 by Taq
09-28-2022 6:07 PM


Re: Keeps going and.going
Taq:
Google "evolutionary pathway". Start reading.
I don't need to, I already know how to do the mathematics of evolutionary pathways. You should learn how to do that math as well, you being a microbiologist and all.
Kleinman:
Are implying that bacteria and humans both don't have DNA?
Taq:
What does the evolution of antibiotic resistance in bacteria have to do with human evolution?

You need to learn that the mathematics of the evolution of adaptive alleles is the same for all replicators, neither ploidy nor recombination changes that fact. You just won't accept that fact because it refutes the notion of universal common descent.
Kleinman:
Did you write something about how mutations take a pathway?
Taq:
I wrote this:

I already explained this a previous post. Let's use an effective population size of 20,000 as described above. That would be 80,000 generations to fix a neutral allele, and at 25 years per generation that would be 2 million years. This means the earliest populations in the human lineage that had just split away from the chimp population would be fixing neutral mutation that occurred 2 million years before that. Every generation after that would be fixing neutral mutations that occurred 2 million years before them. Where is the problem?

And this:

Given your lack of response, are you tacitly agreeing that we should see fixation of neutral mutations in each generation?

Or are you still so confused that you think only 1 mutation can move towards fixation at a time, and that all other neutral mutations can not begin to move towards fixation until that 1 neutral mutation is fixed?

Why don't you try to model a real experiment such as the Kishony or Lenski experiment? Describe how the evolutionary pathway works in either of those experiments and see if any of your models fit these experiments. That's what a scientist would do.
Kleinman:
So, every member of your population gets the same 54.5 mutations every generation.
Taq:
That's what fixation means.

So every generation every new member of the population gets 54.5 new unique mutations to their genome while 54.5 of the neutral mutations they inherited from their parents are fixed and these same 54.5 neutral mutations are identical to every new member of the population. And the next generation, their offspring will get 54.5 new neutral mutations that are unique to each individual while 54.5 of their inherited neutral mutations will be fixed in every member of the population. And that happens generation after generation for tens of thousands of generations. You have quite an imagination.
Kleinman:
Does every human on earth have the same neutral mutations as every other human?
Taq:
No, they don't. As already described, neutral mutations occur at different points in the past so they are all at different points in their journey towards either being lost or becoming fixed.

How many neutral mutations fixed in the Lenski experiment after 70,000 generations?

This message is a reply to:
 Message 288 by Taq, posted 09-28-2022 6:07 PM Taq has replied

Replies to this message:
 Message 290 by Taq, posted 09-29-2022 10:44 AM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 290 of 2926 (898742)
09-29-2022 10:44 AM
Reply to: Message 289 by Kleinman
09-28-2022 7:53 PM


Re: Keeps going and.going
Kleinman writes:
You need to learn that the mathematics of the evolution of adaptive alleles is the same for all replicators, neither ploidy nor recombination changes that fact.
Then you don't know how the mathematics or biology of adaptive alleles works.
In asexual organisms you can't combine mutations that happen in independent lineages. In sexually reproducing species you can combine mutations that are in contemporaneous genomes. That makes a massive difference in how adaptive alleles evolve.
Why don't you try to model a real experiment such as the Kishony or Lenski experiment? Describe how the evolutionary pathway works in either of those experiments and see if any of your models fit these experiments. That's what a scientist would do.
So you aren't going to address what I said?
So every generation every new member of the population gets 54.5 new unique mutations to their genome while 54.5 of the neutral mutations they inherited from their parents are fixed and these same 54.5 neutral mutations are identical to every new member of the population.
The 54.5 neutral mutations that fix in each generation would have entered into the gene pool hundreds of thousands or millions of years before they became fixed. Those mutations would have been found in nearly everyone just prior to reaching fixation. Are we agreed?
How many neutral mutations fixed in the Lenski experiment after 70,000 generations?
An asexual species with a very different mutation rate can not accurately model a sexually reproducing species with a different mutation rate.

This message is a reply to:
 Message 289 by Kleinman, posted 09-28-2022 7:53 PM Kleinman has replied

Replies to this message:
 Message 291 by Kleinman, posted 09-29-2022 11:34 AM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 291 of 2926 (898745)
09-29-2022 11:34 AM
Reply to: Message 290 by Taq
09-29-2022 10:44 AM


Re: Keeps going and.going
Kleinman:
You need to learn that the mathematics of the evolution of adaptive alleles is the same for all replicators, neither ploidy nor recombination changes that fact.
Taq:
Then you don't know how the mathematics or biology of adaptive alleles works.

Then why has the math that I"ve presented been able to predict that each step in the Kishony experiment would take a billion replications? This paper was published years before Kishony performed his experiment. And this same math explains why his two drug experiment doesn't work and what it would take for that experiment to work. This math and physics is way over the head of someone trained in microbiology. That's why microbiologists can't explain the physics and mathematics of the evolution of drug resistance.
Taq:
In asexual organisms you can't combine mutations that happen in independent lineages. In sexually reproducing species you can combine mutations that are in contemporaneous genomes. That makes a massive difference in how adaptive alleles evolve.
Taq now thinks that recombination can recombine mutations at the same genetic loci of both parents. How did you get so confused on this subject?
Kleinman:
Why don't you try to model a real experiment such as the Kishony or Lenski experiment? Describe how the evolutionary pathway works in either of those experiments and see if any of your models fit these experiments. That's what a scientist would do.
Taq:
So you aren't going to address what I said?

I'm not interested in some fantasy model that you dredge up in your confused imagination. If you think your ridiculous model fits reality in any way, apply it to a real-world, measured, and repeatable experimental example. You won't because you know you are blowing smoke.
Kleinman:
So every generation every new member of the population gets 54.5 new unique mutations to their genome while 54.5 of the neutral mutations they inherited from their parents are fixed and these same 54.5 neutral mutations are identical to every new member of the population.
Taq:
The 54.5 neutral mutations that fix in each generation would have entered into the gene pool hundreds of thousands or millions of years before they became fixed. Those mutations would have been found in nearly everyone just prior to reaching fixation. Are we agreed?

Do microbiologists know how to computer program? Take your model, and start with a population that has almost identical genomes except for each member in that population has unique random mutations scattered at different sites in the genome. Randomly choose two parents out of that population. Choose a mutation rate. Randomly select portions of each genome and recombine those portions to create a new genome while adding new unique random mutations to that genome based on your chosen mutation rate. Do that to the entire population until you create a new generation of descendants. Repeat that cycle and measure how many neutral mutations are fixed in the population as a function of the number of generations.
Kleinman:
How many neutral mutations fixed in the Lenski experiment after 70,000 generations?
Taq:
An asexual species with a very different mutation rate can not accurately model a sexually reproducing species with a different mutation rate.

You are right about that. Mutations in an asexually reproducing population can only be lost by selection. On the other hand, mutations can be lost in a sexually reproducing population if the wrong allele is passed in the recombination process. So do a computer simulation of your model and see if you can verify your claims.

This message is a reply to:
 Message 290 by Taq, posted 09-29-2022 10:44 AM Taq has replied

Replies to this message:
 Message 292 by Taq, posted 09-29-2022 11:55 AM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 292 of 2926 (898747)
09-29-2022 11:55 AM
Reply to: Message 291 by Kleinman
09-29-2022 11:34 AM


Re: Keeps going and.going
Then why has the math that I"ve presented been able to predict that each step in the Kishony experiment would take a billion replications?
The mistake you keep making is in forgetting that sexually reproducing species merge lineages. You keep claiming that beneficial mutations have to happen sequentially in an isolated lineage. This isn't the case in sexually reproducing populations. You also make the mistake of thinking every single adaptation will have the same rate as antibiotic resistance. There is no reason to think this is true as shown by a thousand fold difference for the rate of antibiotic and phage resistance in E. coli.
Taq now thinks that recombination can recombine mutations at the same genetic loci of both parents. How did you get so confused on this subject?
Where did I ever say that?????
You are aware that there is more than one gene in the human genome, right?
You are aware that beneficial mutations can happen in different genes, right?
I'm not interested in some fantasy model that you dredge up in your confused imagination. If you think your ridiculous model fits reality in any way, apply it to a real-world, measured, and repeatable experimental example. You won't because you know you are blowing smoke.
Then all you have is denial.
Do microbiologists know how to computer program? Take your model, and start with a population that has almost identical genomes except for each member in that population has unique random mutations scattered at different sites in the genome. Randomly choose two parents out of that population. Choose a mutation rate. Randomly select portions of each genome and recombine those portions to create a new genome while adding new unique random mutations to that genome based on your chosen mutation rate. Do that to the entire population until you create a new generation of descendants. Repeat that cycle and measure how many neutral mutations are fixed in the population as a function of the number of generations.
I already showed you the model. It's the equations for fixation of neutral mutations.

This message is a reply to:
 Message 291 by Kleinman, posted 09-29-2022 11:34 AM Kleinman has replied

Replies to this message:
 Message 293 by Kleinman, posted 09-29-2022 12:57 PM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 293 of 2926 (898749)
09-29-2022 12:57 PM
Reply to: Message 292 by Taq
09-29-2022 11:55 AM


Re: Keeps going and.going
Kleinman:
Then why has the math that I"ve presented been able to predict that each step in the Kishony experiment would take a billion replications?
Taq:
The mistake you keep making is in forgetting that sexually reproducing species merge lineages. You keep claiming that beneficial mutations have to happen sequentially in an isolated lineage. This isn't the case in sexually reproducing populations. You also make the mistake of thinking every single adaptation will have the same rate as antibiotic resistance. There is no reason to think this is true as shown by a thousand fold difference for the rate of antibiotic and phage resistance in E. coli.

Well, that is some progress. At least you are admitting that my model of adaptive evolution is correct for asexually replicating organisms. You should also agree that this model is correct for replicators that replicate by mitosis such as cancer cells. Of course, adaptive mutations have to occur sequentially. Don't you believe that a series of microevolutionary changes add up to a macroevolutionary change? That's almost correct. Once you understand that microevolutionary changes are random events, the joint probabilities of these events don't add, you have to use the multiplication rule. And the probability of an adaptive mutation occurring somewhere in an allele depends on the number of replications of that allele. It doesn't matter whether that allele is in an asexual replicator or a sexual replicator. That allele has to replicate and somehow be passed to the offspring. Understand rubberband?
Kleinman:
Taq now thinks that recombination can recombine mutations at the same genetic loci of both parents. How did you get so confused on this subject?
Taq:
Where did I ever say that?????

You are aware that there is more than one gene in the human genome, right?

You are aware that beneficial mutations can happen in different genes, right?

We are talking about the formation of adaptive alleles. Aren't you saying that recombination can take half of one allele with one beneficial mutation from one parent to recombine with the other half of that allele with another beneficial mutation from the other parent to give an allele with two beneficial mutations? Is that what you mean when you say that beneficial mutations don't have to happen sequentially?
Kleinman:
I'm not interested in some fantasy model that you dredge up in your confused imagination. If you think your ridiculous model fits reality in any way, apply it to a real-world, measured, and repeatable experimental example. You won't because you know you are blowing smoke.
Taq:
Then all you have is denial.

That and a model of adaptive evolution that fits the experimental data, a published model of random recombination, and an understanding of the physics and mathematics of biological evolution. You should try and learn it, you might understand the subject of microbiology better.
Kleinman:
Do microbiologists know how to computer program? Take your model, and start with a population that has almost identical genomes except for each member in that population has unique random mutations scattered at different sites in the genome. Randomly choose two parents out of that population. Choose a mutation rate. Randomly select portions of each genome and recombine those portions to create a new genome while adding new unique random mutations to that genome based on your chosen mutation rate. Do that to the entire population until you create a new generation of descendants. Repeat that cycle and measure how many neutral mutations are fixed in the population as a function of the number of generations.
Taq:
I already showed you the model. It's the equations for fixation of neutral mutations.

Kimura compared his mathematical model of fixation with a computer simulation. Why don't you? Don't worry Taq, I know you won't do this, you are just blowing smoke. So what do you want to do next, learn the mathematics of random recombination or the mathematics of adaptive evolution to multiple simultaneous selection pressures?

This message is a reply to:
 Message 292 by Taq, posted 09-29-2022 11:55 AM Taq has replied

Replies to this message:
 Message 294 by Taq, posted 09-29-2022 4:09 PM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 294 of 2926 (898766)
09-29-2022 4:09 PM
Reply to: Message 293 by Kleinman
09-29-2022 12:57 PM


Re: Keeps going and.going
Kleinman writes:
At least you are admitting that my model of adaptive evolution is correct for asexually replicating organisms.
I've agreed all along that your model for asexual organisms based on the Kishony and Lenski experiments is accurate for asexual organisms. What I keep telling you is that it isn't an accurate model for sexual species like humans.
Of course, adaptive mutations have to occur sequentially.
No, they don't have to. You can have multiple adaptive mutations that are all moving towards fixation at the same time. Even as those beneficial mutations move towards fixation, new beneficial mutations can occur and begin to move towards fixation.
Once you understand that microevolutionary changes are random events, the joint probabilities of these events don't add, you have to use the multiplication rule.
You also have to figure in the number of possible beneficial mutations at any point in the history of a lineage. How many times have I pointed this out?
The mistake you keep making is that you pretend as if only 1 beneficial mutation can move towards fixation at a time. That's wrong. Do you understand why that is wrong?
Aren't you saying that recombination can take half of one allele with one beneficial mutation from one parent to recombine with the other half of that allele with another beneficial mutation from the other parent to give an allele with two beneficial mutations?
Can you just for a moment realize that there is more than one gene in a genome? Please?
Imagine that there is a new beneficial mutation in gene A and a new beneficial mutation in gene B in the same generation. They are on different chromosomes. Both beneficial mutations start moving towards fixation at the same time. Let's say that both mutations reach 5% of the population. This means there is a 0.05*0.05 = 0.025 chance that out of two parents each will have one of the beneficial mutations. Let's say they are both heterozygous for their individual mutations. This means that 25% of their offspring WILL HAVE BOTH MUTATIONS. Do you see how this works?
While these two mutations are moving towards fixation and increasingly found in the same genomes, there will be new beneficial mutations that are appearing, and they too will go through the same process and be combined with the beneficial mutations already in the population.
That and a model of adaptive evolution that fits the experimental data, a published model of random recombination, and an understanding of the physics and mathematics of biological evolution. You should try and learn it, you might understand the subject of microbiology better.
I understand it just fine. The fact you don't understand the difference between asexual and sexual reproduction means you are the one who needs to catch up.
Kimura compared his mathematical model of fixation with a computer simulation. Why don't you? Don't worry Taq, I know you won't do this, you are just blowing smoke. So what do you want to do next, learn the mathematics of random recombination or the mathematics of adaptive evolution to multiple simultaneous selection pressures?
Can you be even more of a douchebag? You can't even understand how chromosomes work, and you want to critique me for not creating a whole program? Give me a break.

This message is a reply to:
 Message 293 by Kleinman, posted 09-29-2022 12:57 PM Kleinman has replied

Replies to this message:
 Message 295 by Kleinman, posted 09-29-2022 6:00 PM Taq has replied
 Message 311 by Kleinman, posted 10-02-2022 2:59 PM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 295 of 2926 (898769)
09-29-2022 6:00 PM
Reply to: Message 294 by Taq
09-29-2022 4:09 PM


Re: Keeps going and.going
Kleinman:
At least you are admitting that my model of adaptive evolution is correct for asexually replicating organisms.
Taq:
I've agreed all along that your model for asexual organisms based on the Kishony and Lenski experiments is accurate for asexual organisms. What I keep telling you is that it isn't an accurate model for sexual species like humans.

You are getting this wrong Taq. Recombination does not create new alleles, it only shuffles existing alleles. And any time a particular allele is replicated and passed on to the offspring, there is a chance for a beneficial mutation occurring on that allele. Instead of thinking in terms of the replication of the entire genome as the random trial, think in terms of the allele being replicated as the random trial. Then in the "at least one" probability calculation, "n" becomes the number of replications of the (potential) resistance allele instead of the number of replications of the subpopulation with that resistance allele. Once different resistance alleles at different genetic loci have evolved, then you have the possibility of a resistance allele for one selection condition at a particular genetic locus in one parent recombining with a different resistance allele for a different selection condition at a different particular genetic locus from the other parent appearing in the offspring. That probability depends on the frequency of the different alleles in the population. Bottom line, the mathematics of the formation of the resistance alleles in asexual replicators is the same for sexually reproducing replicators. Recombination has no significant effect on this process, that's why combination therapy works for the treatment of HIV, combination herbicides, and combination pesticides work despite they are being used on replicators that do recombination. The probability of a recombination event defeating combination herbicides and pesticides occurs only under very specific conditions.
Kleinman:
Of course, adaptive mutations have to occur sequentially.
Taq:
No, they don't have to. You can have multiple adaptive mutations that are all moving towards fixation at the same time. Even as those beneficial mutations move towards fixation, new beneficial mutations can occur and begin to move towards fixation.

Different adaptive alleles can increase in frequency in a population if each of the alleles give increased reproductive fitness for each of the variants. But that doesn't happen because the selection pressure for the variant that doesn't have the resistance allele for that pressure is inhibiting its reproduction, and visa versa for the other variant with the other resistance allele. That's why combination therapy works for the treatment of HIV. Variants with resistance alleles to one drug or another don't get any significant improvement in reproductive fitness so they don't reproduce any better than variants without resistance alleles.
Kleinman:
Once you understand that microevolutionary changes are random events, the joint probabilities of these events don't add, you have to use the multiplication rule.
Taq:
You also have to figure in the number of possible beneficial mutations at any point in the history of a lineage. How many times have I pointed this out?

The mistake you keep making is that you pretend as if only 1 beneficial mutation can move towards fixation at a time. That's wrong. Do you understand why that is wrong?

Have you read this paper?
The basic science and mathematics of random mutation and natural selection
In this paper, I modeled the results Weinreich obtained and published in Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins.
From The_Basic_Science:
What this empirical example demonstrates is that the sequence of mutations must occur in an order of ever increasing fitness in order for the evolutionary process to have a reasonable chance of occurring. In addition, this example demonstrates that there is more than a single sequential order, which can occur. In other words, not every member of the population must have the same sequence of mutations in order to evolve resistance to the antibiotic selection pressure. The population of bacteria has subdivided into subpopulations, each taking their own trajectory to achieve resistance to this particular selection pressure.
If we label one subpopulation ‘1’, that subpopulation must get mutation A1 followed by mutation B1, in turn followed by mutation C1, then D1 and finally E1 in order to evolve resistance to the antibiotic selection pressure. If we label another subpopulation ‘2’, that subpopulation must get a different set of mutations, which we can label A2 followed by mutation B2, in turn followed by mutation C2, then D2 and finally E2 in order to evolve resistance to the antibiotic selection pressure. Each of the subpopulations that Weinreich and his co-authors describe has their own set of mutations, which lead to the evolution of a high-resistance ????-lactamase allele. Each of the subpopulations are evolving independently of the other subpopulations. Once a particular subpopulation starts on an evolutionary trajectory, the replication of members from that subpopulation do not contribute to trials for the next beneficial mutation in a different subpopulation on a different evolutionary trajectory.
Replications of variants in subpopulation 1 do not change the probability of an adaptive mutation occurring in subpopulation 2. Each lineage is on its own particular evolutionary trajectory. That's why the different lineages in the Lenski experiment do not have identical genetic sequences. The population in one vial is taking a different evolutionary trajectory to improved fitness from populations in other vials. What these lineages do have in common is the number of generations to fixation and adaptation for each evolutionary step.
Kleinman:
Aren't you saying that recombination can take half of one allele with one beneficial mutation from one parent to recombine with the other half of that allele with another beneficial mutation from the other parent to give an allele with two beneficial mutations?
Taq:
Can you just for a moment realize that there is more than one gene in a genome? Please?

Of course, I know that. What you are doing is conflating the DNA adaptive evolutionary process and recombination. They are two different physical process with two different mathematical behaviors. Can you just for a moment realize that recombination does not create new alleles? Please?
Taq:
Imagine that there is a new beneficial mutation in gene A and a new beneficial mutation in gene B in the same generation. They are on different chromosomes. Both beneficial mutations start moving towards fixation at the same time. Let's say that both mutations reach 5% of the population. This means there is a 0.05*0.05 = 0.025 chance that out of two parents each will have one of the beneficial mutations. Let's say they are both heterozygous for their individual mutations. This means that 25% of their offspring WILL HAVE BOTH MUTATIONS. Do you see how this works?

While these two mutations are moving towards fixation and increasingly found in the same genomes, there will be new beneficial mutations that are appearing, and they too will go through the same process and be combined with the beneficial mutations already in the population.
Finally, you are starting to think about the mathematics of recombination. Your calculation is off by a factor of 2.
Kleinman:
That and a model of adaptive evolution that fits the experimental data, a published model of random recombination, and an understanding of the physics and mathematics of biological evolution. You should try and learn it, you might understand the subject of microbiology better.
Taq:
I understand it just fine. The fact you don't understand the difference between asexual and sexual reproduction means you are the one who needs to catch up.

When will you learn that recombination does not create new alleles?
Kleinman:
Kimura compared his mathematical model of fixation with a computer simulation. Why don't you? Don't worry Taq, I know you won't do this, you are just blowing smoke. So what do you want to do next, learn the mathematics of random recombination or the mathematics of adaptive evolution to multiple simultaneous selection pressures?
Taq:
Can you be even more of a douchebag? You can't even understand how chromosomes work, and you want to critique me for not creating a whole program? Give me a break.

I forgive you for this because you don't know what you are doing. I've had years of training and years of experience doing mathematical modeling of physical systems and have been paid a lot of money for doing this. One of the tasks when developing a mathematical model is to test its validity by comparing it against other mathematical models and see if they give consistent results. You then test the model against experimental data and see if it gives consistent results with the data produced by the model. You make a claim and put out results that don't agree with the simple neutral fixation equation and Kimura's result when those two models give results in the same order of magnitude. At least now in your post, you are making an attempt to do the mathematics of recombination. Your attempt is off by a factor of two. Try doing a systematic analysis to figure out why. I'll help you by formulating the physical problem:
Consider the following: Assume that we have a population of sexual replicators doing random recombination. Assume that the population size is size ‘n’. In this population, assume that some members of the population have a beneficial allele for one selection condition, call this allele ‘A’. Other members of the population have a beneficial allele for a second selection condition, call this allele ‘B’. The remaining members of the population have neither allele A nor allele B, call these non-A and non-B alleles ‘C’. If a member of the population with beneficial allele A at one genetic locus meets another member of the population with beneficial allele B at a different genetic locus, we assume that these members will recombine giving an offspring with both alleles A and B and thus, a more fit member of the population. The probability that a member of the population with allele A meets and recombines randomly with a member with allele B can then be computed using the principles of probability theory.
The probability distribution for this empirical example is identical to the probability distribution given for random card drawing when there are only three different cards in the deck, A, B, and C. Let:
n – is the total population size.
nA – is the number of members in the population with beneficial allele A.
nB – is the number of members in the population with beneficial allele B.
nC – is the number of members in the population that have neither beneficial allele A nor beneficial allele B.
What is the probability distribution for this problem and compute the (correct) probability of an A member recombing with a B member to give an AB offspring.

This message is a reply to:
 Message 294 by Taq, posted 09-29-2022 4:09 PM Taq has replied

Replies to this message:
 Message 296 by Taq, posted 09-29-2022 7:02 PM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 296 of 2926 (898772)
09-29-2022 7:02 PM
Reply to: Message 295 by Kleinman
09-29-2022 6:00 PM


Re: Keeps going and.going
Kleinman writes:
Once different resistance alleles at different genetic loci have evolved, then you have the possibility of a resistance allele for one selection condition at a particular genetic locus in one parent recombining with a different resistance allele for a different selection condition at a different particular genetic locus from the other parent appearing in the offspring.
Except that we are not talking about antibiotic resistance in humans. We are talking about adapting to an open savanna. There are going to a lot of different pathways that evolution can take. It isn't anything like antibiotic resistance which is very constrained as to where beneficial mutations can occur. The two selection regimes are very, very different.
You are also ignoring diploidy. You don't even need recombination to get two different beneficial alleles. You just need both mutations from separate parents.
Bottom line, the mathematics of the formation of the resistance alleles in asexual replicators is the same for sexually reproducing replicators. Recombination has no significant effect on this process, that's why combination therapy works for the treatment of HIV, combination herbicides, and combination pesticides work despite they are being used on replicators that do recombination.
Multidrug strategies work because there is very strong selection. If you don't have resistance to all drugs at a moments notice then you don't reproduce. That was not the case for human evolution. Our ancestors could survive just fine without the adaptations we have now. The adaptations they did receive allowed them to slowly move out to an open savanna.
This is another feature you are ignoring.
Different adaptive alleles can increase in frequency in a population if each of the alleles give increased reproductive fitness for each of the variants. But that doesn't happen because the selection pressure for the variant that doesn't have the resistance allele for that pressure is inhibiting its reproduction, and visa versa for the other variant with the other resistance allele.
NO, THAT ISN'T WHAT HAPPENS IN EUKARYOTES. You still don't understand how sexual reproduction works. What you are describing is what happens in asexual species, not sexual ones.
In this paper, I modeled the results Weinreich obtained and published in Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins.
Again, you can't use asexual organisms to model sexual organisms. Please learn how sexual selection works. Also, remember that there is more than one gene in a genome.
Replications of variants in subpopulation 1 do not change the probability of an adaptive mutation occurring in subpopulation 2. Each lineage is on its own particular evolutionary trajectory.
Please learn how sexual reproduction works.
What you are doing is conflating the DNA adaptive evolutionary process and recombination. They are two different physical process with two different mathematical behaviors. Can you just for a moment realize that recombination does not create new alleles? Please?
Can you realize for just a moment that beneficial mutations can happen in more than one gene at a time?
I've had years of training and years of experience doing mathematical modeling of physical systems and have been paid a lot of money for doing this.
Where have you ever done a model for two beneficial mutations on separate chromosomes, each of which is moving towards fixation? What would that look like?

This message is a reply to:
 Message 295 by Kleinman, posted 09-29-2022 6:00 PM Kleinman has replied

Replies to this message:
 Message 298 by Kleinman, posted 09-29-2022 8:46 PM Taq has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 297 of 2926 (898775)
09-29-2022 7:40 PM


Multi-Locus Adaptations
A paper modeled multiple genes that were under selective pressure:
quote:
The allele frequencies at the neutral locus remained relatively stable during the simulation, showing small fluctuations due to genetic drift and gene flow between demes (Figure 5a-d, “LocusD”). The allele frequencies at the adaptive loci showed monotonic increasing or decreasing trends depending on the value of the selective environmental variable in the deme (salinity). For example, in deme 1 (high salinity, x = 38.5; Figure 5b), the frequency of the salinity-tolerant alleles increased and reached unity at all three adaptive loci in about 50 years (Figure 6). In deme 69 (low salinity, x = 32.4), the frequency of the salinity-tolerant alleles decreased to about 0.2 in the same time (Figure 6). These dynamics were driven by strong directional selective pressure at the adaptive loci due to extreme salinity values. Different replicates of the simulations produced the same results (not shown).
Just a moment...
As shown in the paper, all beneficial alleles increased in number with each other. One did not outcompete another, nor do they have to. Why? Sexual reproduction.
And this is just for adaptation to one challenge. The same would apply to adaptations that tackle different challenges. For example, lighter skin color allows humans to produce more vitamin D at higher latitudes. Mutations in the promoter region of the lactase gene allows humans to drink cow's milk in adulthood. These are two different adaptations at two different loci. Did one have to displace the other? No! Both beneficial alleles are driven towards fixation together, and they end up in the same genomes.

Replies to this message:
 Message 299 by Kleinman, posted 09-29-2022 9:09 PM Taq has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 298 of 2926 (898780)
09-29-2022 8:46 PM
Reply to: Message 296 by Taq
09-29-2022 7:02 PM


Re: Keeps going and.going
Kleinman:
Once different resistance alleles at different genetic loci have evolved, then you have the possibility of a resistance allele for one selection condition at a particular genetic locus in one parent recombining with a different resistance allele for a different selection condition at a different particular genetic locus from the other parent appearing in the offspring.
Taq:
Except that we are not talking about antibiotic resistance in humans. We are talking about adapting to an open savanna. There are going to a lot of different pathways that evolution can take. It isn't anything like antibiotic resistance which is very constrained as to where beneficial mutations can occur. The two selection regimes are very, very different.

There are not many selection conditions on a savanna, but a few, are starvation, dehydration, thermal stress (both excessively high and excessively low temperatures), disease (bacterial, fungal, parasitic, viral), toxins, and predation, to list a few. It would be sad for some member of the population to get an adaptive mutation that would give a step toward standing upright and end up dying of tetanus or starvation or any of the myriad of other selection conditions that member would face. There wouldn't be much of an improvement in fitness from that first mutation. And the selection condition doesn't change the math, it only changes the target gene(s) as demonstrated by the different selection conditions use in the Kishony and Lenski experiments. It is the number of selection conditions acting on the population that forces the probability down that a lineage can get all the mutations to improve fitness against all the selection conditions. Each additional selection condition introduces another instance of the multiplication rule into the math.
Taq:
You are also ignoring diploidy. You don't even need recombination to get two different beneficial alleles. You just need both mutations from separate parents.
If both parents are homozygous for the resistance allele, then you are doing 2 random trials for the next adaptive mutation in that replication. The haploid replicator gets only one trial with its replication. And you know that doubling the number of replications does not double the probability of an adaptive mutation occurring on one of those alleles. That particular adaptive allele will have to be replicated about 1/(mutation rate) times to give a reasonable probability that one of those replications give the next adaptive mutation. If the parents are heterozygous, then you don't even get the mathematical benefit of diploidy.
Kleinman:
Bottom line, the mathematics of the formation of the resistance alleles in asexual replicators is the same for sexually reproducing replicators. Recombination has no significant effect on this process, that's why combination therapy works for the treatment of HIV, combination herbicides, and combination pesticides work despite they are being used on replicators that do recombination.
Taq:
Multidrug strategies work because there is very strong selection. If you don't have resistance to all drugs at a moments notice then you don't reproduce. That was not the case for human evolution. Our ancestors could survive just fine without the adaptations we have now. The adaptations they did receive allowed them to slowly move out to an open savanna.

This is another feature you are ignoring.

Strong selection actually accelerates adaptive evolution, it removes all the drug-sensitive variants from the population and fixing the drug-resistant variants in a very small number of generations. The only reason that single-drug therapy for treating infectious diseases has worked well at all is that most people are immune-competent. Any drug-resistant variants that remain are removed by the patient's own immune system. The reason why drug resistance is so bad in the hospital environment is that they are dealing with sicker patients, many of who are immune compromised. Drug-resistant bacteria appear as a matter of course simply by neutral evolution. All that is needed is for the population size to be large enough that mutations occur at every possible site in the genome (1/(mutation rate) replications) of that variant. The probability of getting variants with resistance alleles at multiple different loci requires an exponentially larger population if done by neutral evolution alone. But evolve a variant resistant to one drug and allow that variant to recover population size, then you will start getting variants with resistance alleles at two genetic loci. Then when that drug fails, go to a third drug... Finally, you will end up with bacteria such as MRSA.
Kleinman:
Different adaptive alleles can increase in frequency in a population if each of the alleles give increased reproductive fitness for each of the variants. But that doesn't happen because the selection pressure for the variant that doesn't have the resistance allele for that pressure is inhibiting its reproduction, and visa versa for the other variant with the other resistance allele.
Taq:
NO, THAT ISN'T WHAT HAPPENS IN EUKARYOTES. You still don't understand how sexual reproduction works. What you are describing is what happens in asexual species, not sexual ones.

Sometimes I think we are talking about different things. Doesn't relative fitness differences of different variants determine which variants increase in frequency and which decrease? The more fit variants increase in frequency and the less fit variants decrease in frequency. And how is this different between asexual replicators and sexually reproducing replicators?
Kleinman:
In this paper, I modeled the results Weinreich obtained and published in Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins.
Taq:
Again, you can't use asexual organisms to model sexual organisms. Please learn how sexual selection works. Also, remember that there is more than one gene in a genome.

You are wrong Taq. The only difference in the math is that for a clonal replicator, each genome replication is one adaptive allele replication. With a diploid sexual replicator, you have two possible adaptive allele replications for each offspring. And that's only true if both parents are homozygous for the resistance allele. If they aren't homozygous, it is a Mendelian genetics calculation if an adaptive allele replication will be added to the probability calculation.
Kleinman:
Replications of variants in subpopulation 1 do not change the probability of an adaptive mutation occurring in subpopulation 2. Each lineage is on its own particular evolutionary trajectory.
Taq:
Please learn how sexual reproduction works.

Please learn how to count.
Kleinman:
What you are doing is conflating the DNA adaptive evolutionary process and recombination. They are two different physical process with two different mathematical behaviors. Can you just for a moment realize that recombination does not create new alleles? Please?
Taq:
Can you realize for just a moment that beneficial mutations can happen in more than one gene at a time?

You aren't ready to do that math yet. First figure out how to do the mathematics of random recombination.
Kleinman:
I've had years of training and years of experience doing mathematical modeling of physical systems and have been paid a lot of money for doing this.
Taq:
Where have you ever done a model for two beneficial mutations on separate chromosomes, each of which is moving towards fixation? What would that look like?

This is the paper that explains how to compute the probability of adaptive mutations occurring at two or more genetic loci.
The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance
You start the calculation by considering the Venn Diagram for a population with a beneficial allele A1 at some locus in the genome and a benficial allele A2 at a different locus in the genome. The rest of the population has neither allele.
The intersection of the two subsets are variants with both the A1 and A2 alleles.
And you still don't get it, competition and fixation slow adaptation. This calculation is all about determining the probability of getting an A1A2 variant as a function of the entire population size. You do this by finding the intersection of the A1 and A2 subsets. This is where another instance of the multiplication rule comes in.
Apparently, you would rather do this calculation rather than the math of random recombination.

This message is a reply to:
 Message 296 by Taq, posted 09-29-2022 7:02 PM Taq has replied

Replies to this message:
 Message 301 by Taq, posted 09-30-2022 10:59 AM Kleinman has replied

  
Kleinman
Member (Idle past 335 days)
Posts: 2142
From: United States
Joined: 10-06-2016


Message 299 of 2926 (898782)
09-29-2022 9:09 PM
Reply to: Message 297 by Taq
09-29-2022 7:40 PM


Re: Multi-Locus Adaptations
Taq:
As shown in the paper, all beneficial alleles increased in number with each other. One did not outcompete another, nor do they have to. Why? Sexual reproduction.
Nope, it is due to the fitness values they use in Table 1. You can get whatever change in frequency you want by manipulating fitness values.
quote:
Selection was implemented through differences in fecundities phi_F and phi_M between the four gametes, calculated using a base fecundity value of 1,000 propagules multiplied by the relative fitness values of Table 1 in Slatkin (1975). We considered two scenarios of selection strength (selection coefficient s = 0.02 and 0.05) and three scenarios of dispersal (standard deviation of dispersal distance σdisp = 0.5, 1 and 2).

This message is a reply to:
 Message 297 by Taq, posted 09-29-2022 7:40 PM Taq has replied

Replies to this message:
 Message 300 by Taq, posted 09-30-2022 10:39 AM Kleinman has replied

  
Taq
Member
Posts: 9972
Joined: 03-06-2009
Member Rating: 5.6


Message 300 of 2926 (898798)
09-30-2022 10:39 AM
Reply to: Message 299 by Kleinman
09-29-2022 9:09 PM


Re: Multi-Locus Adaptations
Kleinman writes:
Nope, it is due to the fitness values they use in Table 1. You can get whatever change in frequency you want by manipulating fitness values.
When they are all under any kind of positive selection they all increase in number, contrary to your claims. You are claiming that only the most fit allele will increase in number and outcompete all of the others. That's not what happens.

This message is a reply to:
 Message 299 by Kleinman, posted 09-29-2022 9:09 PM Kleinman has replied

Replies to this message:
 Message 302 by Kleinman, posted 09-30-2022 11:42 AM Taq has replied

  
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