Kleinman: Four Questions About Evolution

The first part of this is very easy. It is an example of something that @John_Harshman, @evograd, @davecarlson or myself would be able to do very rapidly, in less than an hour, possibly in minutes.

We are asking him to clearly specify a simulation where he and the scientific community think different things will happen. If he is competent and has a legitimate point, this should be easy.

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It really isnā€™t hard to google ā€œSlim 3 evolutionā€ to find this:

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If you can come up with a test case that satisfies the criteria I laid out, maybe we will run it for you.

Unwillingness to even try will provide us all with abundant evidence that you donā€™t have a point. Much bluster. Not much else.

Good luck.

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That is not well specified enough. Moreover, you donā€™t know if we disagree with you or not. Try again.

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Yes there is more needed. Field questions from us now about this.

What is your prediction of what will happen?

What is our prediction? Do we disagree?

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You have not yet demonstrated we are making a different prediction.

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@kleinman do you believe a haploid model is a good approximation for diploids like humans and other mammals?

This! The models presented so far seem simple, non controversial and to be honest, donā€™t sound like theyā€™re breaking new ground.

Aside: Regarding Lenskiā€™s experiment and carrying capacity. Lenskiā€™s experiment is based on serial transfer in batch cultures. At any particular stage, there is a fixed amount of nutrient but that is effectively refreshed for a sub-fraction of the population (about 1% of each tube is subcultured for each of Lenskiā€™s 12 lines. This is an effective population size of roughly 3x10^7 cells/line). Bacteria experience fluctuations of nutrients that start from abundant, progress to growth-limiting, and then back again. The number of bacteria transferred between subsequent flasks (basically, population size) is really a function of the volumes one chooses to use in the experiment. Serial batch propagation behaves much like a continuous culture environment that cycles between chemostat- and turbidostat-like conditions.

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Exactly. Let me repeat @kleinmanā€™s task.

Can any one predict where this experiment is headed? I hypothesize we are heading towards path #4.

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So here is a place we disagree. Diploid populations with recombination do not have a problem with Mullers ratchet. They also can select mutations in parallel. Big difference!

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OK, letā€™s see if you can explain how evolution works in parallel. Letā€™s try and do a simple calculation to understand this process and use hiv as the empirical example since it does recombination. Letā€™s say you have a population of different variants of the virus. Some variants have a beneficial allele to one drug (call that variant ā€œAā€), another variant has a beneficial allele to a second drug (call that variant ā€œBā€) and the remaining variants have neither allele A nor allele B (call those variants ā€œCā€). Let the total population size be N and the number of members with allele A be nA, the number of members with allele B be nB, and the number of members without either allele be nC so that N = nA +nB + nC. What is the probability that a member with allele A recombines with a member with allele B to give an offspring with both alleles A and B.

HIV is not simple example because it is a highly compressed genome and this limits parallel evolution. How about you get back to your task of finding a simulation to prove your point?

So do the math for some replicator that doesnā€™t have a highly compressed genome. Do weeds and insects have highly compressed genomes? Because the math still is the same and there is abundant empirical evidence that weeds and insects do not evolve efficiently to combination selection pressures.

Iā€™m not doing the math for you. Iā€™m asking for a demonstration by simulation.

No. Once againā€¦

Do you want to try reading (and maybe even address) what @swamidass said again, or are you content to just say ā€œyeah I misunderstood, now letā€™s move onā€?

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I see your reading comprehension problem extended beyond @swamidassā€™ comment to mine.

Iā€™ll try and spell it out for you.

Josh challenged you to ā€œidentify a well specified question, answerable with a simulation, where you and the experts here disagree on the results.ā€

That was the challenge.

After he made this challenge (but in the same paragraph, so I can see how you might have got confused), he said that several outcomes are possible if you tried to meet this challenge, and then listed 4 options:

  1. You will not be able to find such a case, which would demonstrate you cannot substabtiate any of your disagreements are salient.
  2. Your prediction on the experimental results could be correct, and ours would be wrong. We would learn something.
  3. Your prediction is wrong, and ours is right. You would learn something.
  4. You will ignore this test of your work, missing your best opportunity in a long time to be heard.

Somehow, you managed to interpret those 4 options as the challenge, and tried to address them all one by one.

Does that make it clearer for you?

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It might help comprehension to bullet out the criteria:

  1. Well specified question.
  2. Answerable with a simulation.
  3. Experts here disagree with @kleinman on the results.

It seems he may be incapable of doing this. Perhaps we open up the task to others here too. Perhaps @evograd or @davecarlson can succeed. In the mean time, Iā€™m realizing that the reality of this experiment exceeded my imagination. We have to add this as a possible hypothesis to test:

  1. @kleinman cannot comprehend the task before him, and needs help from some graduate students in completing it, calling into question just about everything he is saying.
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Iā€™d be happy to try and help with the simulation part in SLiM 3, if the question was well specified, just because Iā€™d be curious to learn how to use some of the more complex aspects of SLiM. Iā€™m no expert on it at the moment, and it would take me a significant amount of time to do it myself from scratch.

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As we discussed, you did not demonstrate we are making a different prediction. What is so hard for you to understand?

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