Annoying creationists

[Dr Richard]

This is an example of recombination and selection, not mutation and selection (something you evolutionists commonly confuse) but let’s see what you are trying to say. Let’s consider a real example of this phenomenon, sickle cell anemia where the heterozygote is more fit in a particular environment. The selection pressure is due to the malaria parasite. I believe that is a single selection pressure.

What Kleinman believes, and what reality actually represents, are of course entirely different things.

I was going to call "Dr" Kleinman on his misunterstanding of malaria before, but frankly got bored and put him on ignore. As Taffer has kindly reposted his mistake, it is worth pointing that the interaction between malaria and the human host is far more complicated than Kleinman's simple interpretation would allow:

Malaria parasite interactions with the human host

Not sure if this journal is freely accessable, so for Kleinman's benefit:

Abstract: The interaction between the malaria parasite and the human host involves a number of interactions that result in the parasite evading the human immune system. Since the stages of the malaria lifecycle are complex, this allows the use of various immune evasion strategies by the malaria parasite and has major implications in the development of a vaccine for malaria endemic areas. The present review highlights key hostarasite interactions. Plasmodia puts selection pressure on human gene frequencies, and studies into host genetic factors such as the Duffy blood group and sickle cell anaemia offer insight into the host- parasite relationship. In addition, parasite interactions with the different effector arms of the immune system can result in altered peptide ligand (APL) antagonism which alters the immune response from a pro- to an anti-inflammatory T cell response. Recent insights into the interaction between professional antigen presenting cells, dendritic cells (DCs), and malaria parasites is discussed in detail.

This is of course the same category of error he makes when asserting that treating an HIV infected patient with three drugs results in three selection pressures, rather than 3550 + 3 (or whatever).

One can only hope that ignorance truly is bliss.

 

[kleinman]

Annoying Creationists

What you are having a hard time understanding is that any random mutation has the potential of moving that creature in any direction on the fitness landscape.

Very Very good. This is true. And only those that are favorable(downhill in the landscape) to survival (or favorable enough) actually pass on the genes and propogate the good. Thank you for repeating back to all of us what we have tried so hard to get you to understand.

Why joobequate, you evolutionary mathematicians are brilliant. But you are not so brilliant to catch an error that both Thabiguy and I have made with respects to the fitness landscape. I had initially thought the fitness landscape has the number of dimensions equal to the number of selection pressures and Thabiguy assigned the number of dimensions to this space as equal to the number of traits that a genome has. Actually, the fitness space has a number of dimensions equal to the genome length plus one. It can actually be greater than this if you allow for insertions or gene duplications. Let’s see if your evolutionist mathematically challenged mind can grasp this?

Your silly twofisted grip on the fistness landscape as verification of your delusions has been amusing to watch. Abandon this lie. It just highlights your inept understanding of science.

What really is silly is that evolutionists like you can imagine a reptile genome on a fitness landscape that transforms into a bird genome. That type of twofooted imagination highlights your inept understand of science, both feet are in your mouth.

Do we know why kleinman is raving about recombination?

The same reason he raves about pretty much anything: he doesn't understand it.

Delphi, how is your sock drawer doing?

That’s a very nice review of review. And note that recombination can not create new genes...

Yes it can, kleinman. Recombination is just another source of variation in a population, and it is this variation which leads to new genes. If mutations can cause new genes to arrise (which it can), so can recombination (which it does).

Really, tell us how recombination makes new genes?

There is no guarantee that a random mutation will move you only up or down slope. A mutation can be neutral and move you along an isocline. You can not uncouple the effects of multiple selection pressures. This is why the search on the fitness landscape is confounded and profoundly slowed when you have multiple selection pressures.

As the fitness function grows in all variables, a mutation that affects more than one trait can only be neutral if enhancing one trait means reducing other traits by the same amount. If this necessarily happens every time, then the traits are by definition inversely correlated, like trying to select for a long tail and for a short tail at the same time. If it doesn't happen necessarily but just by chance, then multiple selection pressures makes it less likely to happen: the isocline is a hyperplane and adding more dimensions makes it less likely to stay on this hyperplane by chance as there are increasingly more directions that lead away from it.

Before we go on, your description of the fitness space is wrong. You described the fitness function as follows:

For multiple selection pressures (say n) the fitness function becomes a function of n variables: f(g) = F(trait-1(g), trait-2(g), ... , trait-n(g)) growing in all variables, i.e. with partial derivative dF/dx(i) > 0 for 1<=i<=n (this expresses the fact that there is actually a selection pressure for each trait).

The fitness landscape actually has the number of dimensions equal to the length of the genome plus one. Each genetic sequence of a genome maps to a point on the fitness landscape. Each locus in the genetic sequence represents a dimension on the fitness landscape, your concept of traits do not represent dimensions on the fitness landscape.

The shape of the fitness landscape is then defined by the selection pressures the creature is subjected to. As an example of how this works, consider the example of the fitness landscape for HIV. That virus has a genome length of about 17,000. The fitness landscape then maps to a 17,000 dimension surface plus one for the value of the fitness function. Each of these 17,000 loci has 4 possible base substitutions. When selection pressures are fixed and you have an optimum genetic sequence for the virus, natural selection has a stabilizing effect on the genetic sequence. However, when you introduce medical treatment of HIV (a new selection pressure), natural selection now becomes directional. If you have only a single selection pressure (monotherapy) it is much easier for natural selection to find a new optimum on the fitness landscape. The search only requires a single direction. However, when you introduce combination therapy (multiple selection pressures), it is much more difficult for natural selection to find new optimums for each of these selection pressures simultaneously. Several directions must be searched simultaneously and this confounds the search.

If you studied ev, you would understand this. If you examined the real cases of combination therapy for the treatment of HIV, combination therapy for the treatment of TB, combination pesticides, combination herbicides, combination rodenticides, you would see real examples of what ev demonstrates and what the fitness landscape requires. Mutation and selection can not and does not do what evolutionists allege, it is mathematically impossible.

Um, [random mutation and natural selection] as programmed in by an intelligent designer.

Ah, so now you're arguing that mutation and/or natural selection cannot arise in nature by naturalistic means? Or are you arguing that the specific type of mutation or selection in Ev might not occur in that exact fashion in nature?

Paul, it’s nice to have you back. Did you spend some more time at the beach contemplating the sun over the water and pondering the wonders of what the primordial soup has done?

Of course ev’s selection process does not work like it does in nature but still is adequate (adebz, you don’t mind if I use this word, do you?) to describe the mathematics of mutation and selection.

 

[kleinman]

Annoying Creationists

This is an example of recombination and selection, not mutation and selection (something you evolutionists commonly confuse) but let’s see what you are trying to say. Let’s consider a real example of this phenomenon, sickle cell anemia where the heterozygote is more fit in a particular environment. The selection pressure is due to the malaria parasite. I believe that is a single selection pressure.

What Kleinman believes, and what reality actually represents, are of course entirely different things.

I was going to call "Dr" Kleinman on his misunterstanding of malaria before, but frankly got bored and put him on ignore. As Taffer has kindly reposted his mistake, it is worth pointing that the interaction between malaria and the human host is far more complicated than Kleinman's simple interpretation would allow:

Malaria parasite interactions with the human host

Not sure if this journal is freely accessable, so for Kleinman's benefit:

Apparently Dr Richard still has not graduated Sesame Street. He still needs a picture drawn for him; he can’t read beyond the abstract if he had, he would have seen.

Sickle cell anaemia allele, severely deleterious in the homozygote, is associated with malaria protection in the heterozygote, possibly due to abnormal RBC shape.

and

Severe malaria, which can lead to neurological sequelae and death may involve CD36-mediated sequestration of parasitised erythrocytes.

This is exactly what I said earlier, homozygotes of the sickle cell allele have sickle cell disease and are selected against, homozygotes with normal hemoglobin in endemic malaria regions get malaria and are selected against while heterozygote of normal and sickle cell hemoglobin do not have sickle cell disease and have malaria protection. Thank you for the reference which verifies what I said but you really do need to finish Sesame Street. Don't forget the part where they teach you how to count.

 

[Thabiguy]

Is there a functional limitation to the number of dimensions which can be run in fitness landscape simulations (i.e hardware limitations)? Or are high n dimension landscapes often run?

Well, it depends on the complexity of the fitness function. I have run evolutionary algorithms on problems with 1000 dimensions that converged within minutes, but that was not serious stuff. If the fitness function is simple enough (addition etc.), conceivably hundreds of thousands of dimensions could be feasible; if it is more complicated, hardware limits may be hit much earlier. For classical von Neumann architecture the complexity would be at least O as all parameters must be at least read, but if it could be parallelized and run on special hardware, time complexity such as O(log n) could be theoretically achieved and one could theoretically evaluate billions of dimensions (other issues would become more limiting here, such as storage and implementation). The computational complexity of the entire problem would also depend on the simulated population size. So there is no general answer, it really very much depends on the specifics of the problem.

But those are issues specific to solving such problems on a computer. As for natural evolution, the "computational complexity" of the fitness function is of course not an issue; the nature "evaluates" it automatically and in parallel for all members of the population.

 

[joobz]

Why joobequate, you evolutionary mathematicians are brilliant. But you are not so brilliant to catch an error that both Thabiguy and I have made with respects to the fitness landscape. I had initially thought the fitness landscape has the number of dimensions equal to the number of selection pressures and Thabiguy assigned the number of dimensions to this space as equal to the number of traits that a genome has.

No, I didn't you incompetent ninny. Stop the lies. I assumed no axes to the multidementional space. My explanations didn't require it.

The mistake I made was to state that beneficial adaptations were a downhill movement. convention in the fitness landscape dictates that peaks represent the locally most fit species.

Actually, the fitness space has a number of dimensions equal to the genome length plus one.

is that plus 1 for god?

 

[Dr Adequate]

Why joobequate, you evolutionary mathematicians are brilliant. But you are not so brilliant to catch an error that ... I have made with respects to the fitness landscape.

Er ... yes we were.

It's in the FAQ, under the heading "Why Lie #5 is funny". I may have mentioned this a few times.

Why do you lie so much, kleinman?

 

[Dr Adequate]

You mathematically challenged evolutionists really like improperly interpreted mathematics.

Whom do you hope to deceive with this stupid lie?

What you are having a hard time understanding is that any random mutation has the potential of moving that creature in any direction on the fitness landscape.

We all know that. Whom do you hope to deceive with this stupid lie?

You are lying to us about what we understand.

So we all know you're lying.

Why do you lie so much, kleinman?

You don’t have independent selection pressures that evolve only up or down slope on the fitness surface.

What do you hope that that jumble of words means?

Selection pressures are the tendency to move up the slope of the fitness landscape. This is because they define the shape of the fitness landscape so that this is true.

Dolt.

Thabiguy has given you a new fantasy trip for you evolutionists to go on, but this one will go into the ever growing evolutionist trash can of bad ideas, like huge populations give marked acceleration of evolution, the mathematics is not there to support this idea.

This is a stupid lie. The mathematics relating to population size exists and is in the FAQ.

Remember how I told you you can't make reality go away by lying?

 

[kleinman]

Annoying Creationists

Is there a functional limitation to the number of dimensions which can be run in fitness landscape simulations (i.e hardware limitations)? Or are high n dimension landscapes often run?

Well, it depends on the complexity of the fitness function. I have run evolutionary algorithms on problems with 1000 dimensions that converged within minutes, but that was not serious stuff. If the fitness function is simple enough (addition etc.), conceivably hundreds of thousands of dimensions could be feasible; if it is more complicated, hardware limits may be hit much earlier. For classical von Neumann architecture the complexity would be at least O as all parameters must be at least read, but if it could be parallelized and run on special hardware, time complexity such as O(log n) could be theoretically achieved and one could theoretically evaluate billions of dimensions (other issues would become more limiting here, such as storage and implementation). The computational complexity of the entire problem would also depend on the simulated population size. So there is no general answer, it really very much depends on the specifics of the problem.

Sure, 1000 dimensions will converge in minutes. That corresponds to a genome length of 1000 in the model. Ev does this easily. It is the larger genome lengths that bog down the search (that and multiple selection pressures). There are some general answers you can give to this mathematical problem. Those general answers are, 1) multiple selection pressures slow down the search, 2) longer genome lengths slow down the search and 3) huge populations do not markedly accelerate the search.

But those are issues specific to solving such problems on a computer. As for natural evolution, the "computational complexity" of the fitness function is of course not an issue; the nature "evaluates" it automatically and in parallel for all members of the population.

Now that is a perfect example of evolutionist hogwash. You think the real world does not work the same way as the mathematics shows. Thabiguy, why don’t you explain to us why combination therapy of HIV doesn’t evolve resistance to all medications as rapidly as monotherapy? Just ignore the mathematics and ignore reality. You evolutionists have no idea how mutation and selection works. If you did, you would understand that your theory is mathematically impossible and reality demonstrates this.

Why joobequate, you evolutionary mathematicians are brilliant. But you are not so brilliant to catch an error that both Thabiguy and I have made with respects to the fitness landscape. I had initially thought the fitness landscape has the number of dimensions equal to the number of selection pressures and Thabiguy assigned the number of dimensions to this space as equal to the number of traits that a genome has.

The mistake I made was to state that beneficial adaptations were a downhill movement. convention in the fitness landscape dictates that peaks represent the locally most fit species.

Convention dictates that evolutionists have no idea of the mathematics of the mutation and selection. That’s the only way you can cling to your ridiculous theory. Reality shows that the mathematics does predict properly the behavior of mutation and selection.

Actually, the fitness space has a number of dimensions equal to the genome length plus one.

is that plus 1 for god?

No, if you understood the mathematics, you would understand that the extra dimension is for the mapping of the value of the fitness function. Don’t alchemical engineers have to study mathematics?

 

[Dr Adequate]

is that plus 1 for god?

I think he's been mislead by the metaphor of a fitness "landscape" into thinking of the output of the fitness function as the "height" of the "landscape", hence another dimension.

---

ETA: I was right --- see his post above.

 

[joobz]

Convention dictates that evolutionists have no idea of the mathematics of the mutation and selection. That’s the only way you can cling to your ridiculous theory. Reality shows that the mathematics does predict properly the behavior of mutation and selection.

Reality does agree with the mathematics. It's actually quite impressive. Luckily, the math used has nothing at all to do with what you are talking. Your random jibberish

No, if you understood the mathematics, you would understand that the extra dimension is for the mapping of the value of the fitness function. Don’t alchemical engineers have to study mathematics?

I was making fun of you...
But your insistance on the defining demensions of the fitness function has presented a new insight into your math. We can ever only use 1 set of dimensions when describing a system. It is impossible to represent a feature using different axes.

Quick, alert all of science that we must abandon Tranforms. We are no longer allowed to use Fourier Transforms, Laplace, Lagandre..... These have no meaning!!!! We can no longer use polar coordinates or, or or..... AHHHHH

 

[joobz]

I think he's been mislead by the metaphor of a fitness "landscape" into thinking of the output of the fitness function as the "height" of the "landscape", hence another dimension.

---

ETA: I was right --- see his post above.

I assumed that was what he was refering to, but i've seen too many mistakes in his reasoning to assume any logic behind his posts.

 

[cyborg]

Quick, alert all of science that we must abandon Tranforms. We are no longer allowed to use Fourier Transforms, Laplace, Lagandre..... These have no meaning!!!! We can no longer use polar coordinates or, or or..... AHHHHH

Well that's my exam screwed then.

Thanks a lot kleinman.

 

[Thabiguy]

Why joobequate, you evolutionary mathematicians are brilliant. But you are not so brilliant to catch an error that both Thabiguy and I have made with respects to the fitness landscape. I had initially thought the fitness landscape has the number of dimensions equal to the number of selection pressures and Thabiguy assigned the number of dimensions to this space as equal to the number of traits that a genome has. Actually, the fitness space has a number of dimensions equal to the genome length plus one. It can actually be greater than this if you allow for insertions or gene duplications. Let’s see if your evolutionist mathematically challenged mind can grasp this?

The fitness landscape actually cannot be meaningfully plotted for a function of the genome itself, as genomes are discrete entities. That's why I preferred to call the fitness landscape a "multi-dimensional graph of fitness function with respect to small changes in the genome that correspond to these individual traits (assuming they are independent)". That's because changes in the genome that affect traits that are not selected for/against do not change the fitness function and are therefore not relevant for the graph of that particular fitness function (it will be constant in those additional dimensions). I have no problem if you want to consider these additional dimensions as well. Add as many as you like.

When selection pressures are fixed and you have an optimum genetic sequence for the virus, natural selection has a stabilizing effect on the genetic sequence. However, when you introduce medical treatment of HIV (a new selection pressure), natural selection now becomes directional. If you have only a single selection pressure (monotherapy) it is much easier for natural selection to find a new optimum on the fitness landscape. The search only requires a single direction. However, when you introduce combination therapy (multiple selection pressures), it is much more difficult for natural selection to find new optimums for each of these selection pressures simultaneously. Several directions must be searched simultaneously and this confounds the search.

Incorrect. A mutation that occurs in a dimension that is not being selected for has no effect on the fitness. What matters are those mutations that occur in the dimensions that are being selected for. There are as many of these dimensions as there are traits considered in the fitness function - the number of selection pressures.

Mutations in a population "search" through all dimensions simultaneously. A dimension is "searched" whenever a mutation occurs in it. If a trait is being selected for, then when the mutation occurs that affects that trait, a "search" is performed in that direction. The probability that this will occur depends on the population size and the mutation rate, but not on the overall number of dimensions. In other words, the length of the genome does not generally affect the probability that a mutation occurs in one particular gene.

If there are multiple dimensions selected for, then a mutation in either of it will affect the fitness function. How soon this will happen depends on the mutation rate; the resulting selection effect depends on the change in the fitness function. None of this depends on the number of dimensions, either total or those selected for.

You must realize that "searching" in this context does not mean going in a direction, exploring the landscape and finding the best value there. Perhaps you are confused by the picture in the Wikipedia article and are interpreting the "search" to mean climbing up the slope and "success" to mean that a local extreme is found. That's not the case; the "search" means searching in the local neighborhood for a direction in which there is any slope. Every time that a slope is found (a mutation occurs that changes the fitness function), the "search" succeeds. Every little arrow on that picture represents a successful "search". And because, as I tried to explain, the dimensions are "searched" simultaneously (the probability of a mutation affecting a trait does not depend on the length of the genome), the speed of that happening is in no way "confounded" by the number of dimensions; it doesn't depend on it.

But the good news is that your understanding of the fitness landscape, while still not accurate, has improved.

 

[kjkent1]

I provided you with citations to peer-reviewed science and you call them bizarre speculations. You just keep proving my point over and over, that you're not interested in anything scientific. This is all about you trying to raise your self esteem.

Post the quote(s) from your peer-reviewed science that you think supports your point.

The point of a peer-reviewed science article is that it reports a hypothesis and the results of an experiment intended to validate or reject that hypothesis (you must have been absent from class the days that your professors explained how scientific research is conducted). If I post an article that shows evidence of HGT, then that’s what it shows. There are only three possible interpretations of the existence of such evidence: (1) two lineages obtained identical genetic sequences by random chance; (2) two lineages obtained identical genetic sequences via some natural process (e.g., retroviral insertion, crossbreeding, etc.); (3) two lineages obtained identical genetic sequences by supernatural/magical intervention.

Choice #1 is possible but scientifically improbable; #2 is scientifically probable and possible; #3 is scientifically impossible.

If you’re a scientist, you will be quickly led to choice #2 as the simplest solution, followed by choice #1 as a remote possibility. If not, then you will choose #3.

Have you considered the seminary? It would seem to suit your apparently illogical thought processes more closely than the scientific disciplines.

Oh yes, you are so right, this is all about raising my self esteem, you silly little gator. This has nothing to do with ev showing the theory of evolution to be mathematically impossible.

If it had anything to do with showing that the theory of evolution is mathematically impossible, then you would produce a research paper proving this hypothesis.

As you choose not to do so, this must be all about raising your self esteem.

So your latest proposal is that horizontal gene transfer is what evolved us from our primate precursor. Now you’ve added another dish to our red herring, string cheese and whine meal, a big bowl of sloshing primordial soup.

As demonstrated above in this post, my proposal has merit, and yours does not – unless you are seeking employment as a medium.

Just turn off all of ev's selection pressures, and all those genes will arise instantly -- just like what must have occurred at the time of abiogenesis, when no selective pressures existed.

Hey, what alternative universe are you in now?

The universe in which kleinman demonstrates maturity in keeping with his credentials.

Now be careful, my self esteem is at stake. Could you pass me another bowl of primordial soup? Maybe the horizontal transfer of a few genes will help my self esteem problem.

I know your self esteem is at stake – otherwise you wouldn’t post in this forum, because nothing that you post here will ever have the effect of proving evolution impossible. As for dishes, you’ve just been served another heaping helping of humble pie.

 

[Dr Adequate]

Thabiguy, why don’t you explain to us why combination therapy of HIV doesn’t evolve resistance to all medications as rapidly as monotherapy?

He did, you just quoted him doing so.

"When using multiple drugs to combat an illness, resistance is less likely to occur, because the population is dramatically reduced, and so the chance of a favorable mutation occurring are reduced."

Which part of that were you too stupid to understand?

Just ignore the mathematics and ignore reality. You evolutionists have no idea how mutation and selection works. If you did, you would understand that your theory is mathematically impossible and reality demonstrates this.

Remember, we all know you're lying.

Convention dictates that evolutionists have no idea of the mathematics of the mutation and selection.

That would be the "convention" that creationists always lie about everything, right?

Reality shows that the mathematics does predict properly the behavior of mutation and selection.

Hey, look, you inadvertantly wrote a whole sentence without a lie in it.

Will you have to sacrifice an extra goat to the Father of Lies to make up for it, or what?

No, if you understood the mathematics, you would understand that the extra dimension is for the mapping of the value of the fitness function. Don’t alchemical engineers have to study mathematics?

If you understood the mathematics, you'd realise that the dependent variable is not one of the dimensions of the optimization problem.

Dolt.

 

[Dr Richard]

Why did I take him off ignore???

Apparently Dr Richard still has not graduated Sesame Street. He still needs a picture drawn for him; he can’t read beyond the abstract if he had, he would have seen...

...selection of quotes missing the point of the article - imagine my surprise

This is exactly what I said earlier,

Just a reminder of what you said earlier Kleinman

Let’s consider a real example of this phenomenon, sickle cell anemia where the heterozygote is more fit in a particular environment. The selection pressure is due to the malaria parasite. I believe that is a single selection pressure.

Why did you ignore:

1. "The gene conferring the Duffy blood group is the most striking example; people of this blood type are completely immune to Plasmodium vivax blood stage infection, as they lack the relevant receptor on RBC membranes."

2. "Inducible nitric oxide synthase 2 (iNOS2) is an enzyme that modulates nitric oxide (NO) production, ultimately affecting malarial immunity"

3. "A polymorphism restricting the affinity of Fc gamma RII to IgG1 and IgG3 has been investigated in Western Kenyans, and correlates with P. falciparum immunity"

4. "Heterozygosity for an allelic variant of CD36 is associated with protection from severe malaria in Africans. Importantly, MHC Class I B53 (MHC-B53), and II DQB1FNx010501 and DRB1FNx011302 alleles are associated with protective clinical responses in African populations."

5. "Natural immunity to malaria takes years to acquire, at least partly due to a very effective immune evasion strategy mediated by naturally occurring variants of the same antigenic epitopes, capable of inhibiting memory T cells [Figure - 2]. This so-called ′altered peptide ligand′ (APL) antagonism affects specific cell lysis and lymphocyte proliferation, as well as cytokine production."

6. "It is reasonable to assume that DCs also play a critical role in initiating immune responses to malaria"

All of which highlight different mechanisms of malaria parasite/human host interaction, all of which are subject to separate selection pressures as all are capable of varying independently within the gene pools of humans and MPS.

So, I refute your claim, quoted again above, that

The selection pressure is due to the malaria parasite. I believe that is a single selection pressure.

The "malaria parasite" is exerting a selection pressure. It is not single, unless you sum selection pressures.

 

[Dr Adequate]

There are some general answers you can give to this mathematical problem. Those general answers are, 1) multiple selection pressures slow down the search, 2) longer genome lengths slow down the search and 3) huge populations do not markedly accelerate the search.

I have some bad news for you.

All these "general answers" are wrong.

 

[Thabiguy]

Thabiguy, why don’t you explain to us why combination therapy of HIV doesn’t evolve resistance to all medications as rapidly as monotherapy?

Because 1) viral load is dramatically reduced, thus the probability that any given mutation will occur in the population, 2) selection pressure for any individual resistance is lower in combination therapy than in monotherapy, because it no longer offers such a significant survival advantage. Only developping resistance to all medications is strongly selected for, and that is less likely. But it will eventually occur.

 

[Dr Adequate]

Because 1) viral load is dramatically reduced, thus the probability that any given mutation will occur in the population, 2) selection pressure for any individual resistance is lower in combination therapy than in monotherapy, because it no longer offers such a significant survival advantage. Only developping resistance to all medications is strongly selected for, and that is less likely. But it will eventually occur.

I'm not sure about your point 2, because surely what matters is the relative advantage.

Point 1 is clearly right. It's not the fact of multiple selection pressures that makes triple therapy better than giving the three drugs sequentially, it's that these are also demographic pressures.

If population is constant, multiple simultaneous non-conservative selection pressures increase the rate of adaptive evolution compared to the case where they occur in sequence.

 

[Thabiguy]

I'm not sure about your point 2, because surely what matters is the relative advantage.

I may be wrong about this. I'm frankly not familiar with the exact mechanism of the antiretroviral action against HIV. I can imagine a few macroscopic scenarios where the relative advantage could be reduced (a person shooting wolves unless they're white and have curly fur; because it would take a long time for such a wolf to appear, it would also take a long time for the white color to be of any advantage, compared to curly fur not being a criterion), so I was willing to give this point to Kleinman. If I am indeed wrong, all the worse for his theories.