Is There Enough Time For Humans to Have Evolved From Apes? Dr. Ann Gauger Answers

_{Denyse O'Leary

November 5, 2012

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That means, of course, that we are really looking at the mutations along a single family line, so to speak, correct? No. Each locus has its own "family line" as recombination scrambles them. Fixed means fixed, gone from a frequency of 1/N to 1, taken over the population or become the only allele at a given locus. Again, this is intro to pop. gen. stuff, read a good text book if you don't think I'm playing straight. So that brings us back to one of the early questions on this thread: at what point and in what instances do we need coordinated (or specified, if you will) mutations to get to humans (as opposed to a simple additive model of unspecified mutations along a lineal descent line)? Well, yeah, that's the question Gauger is begging.wd400_{November 12, 2012
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wd400:
In you hypothetical population each generation would see (on average) 10 new fixations. That’s because each of the 50 new mutations arising in each generation would have a 1/5 chance of eventually fixing (note, it wouldn’t be the 50 mutations entering the population today that get fixed, the average time to fixation is 4Ne = 20 generations in this case). This is the actual number of fixations that will occur over time. The substitution rate is equal to the mutation rate, not the same thing as the mutation rate.
Thanks. I understand where you're coming from on the raw calculation. I think I also understand now how you are using the term "fixed." I believe you are saying that because humans can theoretically be traced back to a single individual in any given generation, then by definition, whatever mutations that individual had at the time will later be included in the entire later population because, again by definition, that individual was the ancestor of the final generation of organisms we are currently looking at. That means, of course, that we are really looking at the mutations along a single family line, so to speak, correct? We define the line after-the-fact, based on whatever organism in each generation happens to have been the progenitor of the now-existing population. We could perhaps probe this in more depth to see how it holds up in specific instances, but I think I understand the approach and it should suffice for the present discussion. (I presume we are also in agreement that this form of becoming "fixed" in a lineal descent simply by virtue of a particular organism being the progenitor of a later population is different from the concept of a mutation becoming "fixed" in a relatively contemporaneous population of multiple organisms?) So that brings us back to one of the early questions on this thread: at what point and in what instances do we need coordinated (or specified, if you will) mutations to get to humans (as opposed to a simple additive model of unspecified mutations along a lineal descent line)?Eric Anderson_{November 12, 2012
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wd400 proves that it does NOT understand science:
Tell me how the substitution rate could not be equal to the mutation rate for neutrally evolving variants.
Umm it is up to YOU to demonstrate that it is. There isn't any "proving a negative", YOU need POSITIVE evidence to support YOUR claims and you don't have any. I keep asking for positive evidence and instead of producing any all you do is repeat yourself. That is a sure sign of dishonesty or insanity.Joe_{November 12, 2012
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p.s. If it is a probabilistic argument, then 1 > p > 0 right? So you're not saying something must happen, only that it will probably happen, with frequency f.Mung_{November 11, 2012
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wd400:
Call be a Bayesian, but pretty much all interesting arguments are probabilistic.
Nah, not name calling. I'm talking about the mathematics behind fixation (substitution) that you've been referring to. A given mutation in a population of size x which continues to reproduce at rate y with the population size remaining constant reaches fixation with probability z... The probability that a new mutation will disappear from the population in the first generation after it first appeared is d... Even a beneficial mutation will be lost with probability b... All that stuff. The mathematics don't cause a mutation to become fixed, they merely describe the probabilities given certain assumptions. Or am I full of it? ;) Probably.Mung_{November 11, 2012
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Joe. Tell me how the substitution rate could not be equal to the mutation rate for neutrally evolving variants. Until you can do that I'll keep you in them mental killfile.wd400_{November 11, 2012
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wd400:
If it isn’t entirely clear to you know, I’m ignoring you because you are a math denier.
You are a false accuser as I do NOT deny any math. I say that you have never shown that your math is correct. Huge differnce but one that proves that you are an intellectual coward. So ignore me all you want I will still be here making sure that people see you for what you are.
What possible reason is there to talk to someone who won’t even accept the most basic findings of the field we’re meant to be discussing?
Except there aren't any findings. Population genetics works backwards- that is how the equations were formulated- Ann goes over that in the book "Scuence & Human Origins".Joe_{November 11, 2012
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Eric, In you hypothetical population each generation would see (on average) 10 new fixations. That's because each of the 50 new mutations arising in each generation would have a 1/5 chance of eventually fixing (note, it wouldn't be the 50 mutations entering the population today that get fixed, the average time to fixation is 4Ne = 20 generations in this case). This is the actual number of fixations that will occur over time. The substitution rate is equal to the mutation rate, not the same thing as the mutation rate. Mung, Call be a Bayesian, but pretty much all interesting arguments are probabilistic.wd400_{November 11, 2012
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It a probabilistic argument, and we all know how fau;lty those are. ;)Mung_{November 11, 2012
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wd400 @75: Thanks for your patience. Perhaps you can help me clarify one more thing, based on a very simple example. If we have a population of 5 organisms and they have each experienced 10 mutations randomly in the genome, you appear to be saying that the population has now "fixed" 10 new mutations in the population. While that may be true as some kind of abstract average across the population, it is unlikely that any particular mutation in one organism (call it organism 'A') even shows up in any of the other organisms. So in that sense, the new alleles of A are not fixed across the population, correct? It would only be unless and until the mutations experienced by A provided a survival advantage under sufficient selection pressure over time that the alleles of A would become pervasive in the population and supplant the corresponding non-mutated alleles. I'm wondering if we are back to the issue of (i) the abstract number of overall unspecified mutations vs. (ii) actual specific mutations that have become pervasive in the population.Eric Anderson_{November 11, 2012
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Mung @81: We do have at least some information on current rates of mutation in humans. That is the 65 point mutations (SNP's essentially) per generation number wd400 and I have been using for purposes of discussion. This is a rough number for simplicity, but corresponds reasonably well to some studies looking at mutations across several generations of a single family line. According to the data Dr. Noor used for his class, this number varies considerably, depending primarily on the age of the father (i.e., older father at time of conception means more mutations, on average). However, for purposes of discussion, I think this number gives us a decent start. I should add that this rate is almost certainly too high if we are using a small generation time of, say, 15 years, as wd400 has been doing, because fewer mutations would be expected with more youthful parents (we probably should be using something more like 40 or 45 point mutations per generation). That would change wd400's numbers by about 1/3, but it is not an order of magnitude thing (at least as long as we are doing simple additive mutation calculations and not exponential calculations). Again, for purposes of discussion I've been willing to concede 65 mutations/generation, as it corresponds reasonably well with current known rates for somewhat older parents. As to the time of divergence between humans and chimps, my understanding of what wd400 is saying is that the timeframe is calculated based on known mutation rates (I don't know the current chimp mutation rate offhand, but presumably that figure is out there). -----
So we’re not just talking about any mutation to any stretch of DNA. We’re talking about mutation with an effect. Appealing to a vast number of mutations that do nothing in order to explain differences between humans and their alleged ancestors somehow seems wrong to me.
Indeed.Eric Anderson_{November 11, 2012
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Mung, the pre-specified mutation would take 10 000 generations to occur (ignoring standing variation for now). Neutral mutations can have an effect, of course. Joe, If it isn't entirely clear to you know, I'm ignoring you because you are a math denier. What possible reason is there to talk to someone who won't even accept the most basic findings of the field we're meant to be discussing?wd400_{November 11, 2012
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Gauger was talking about “one mutation in a DNA binding site.”
A specific mutation. One that's probably required before a DNA sequence can even be expressed. So we're not just talking about any mutation to any stretch of DNA. We're talking about mutation with an effect. Appealing to a vast number of mutations that do nothing in order to explain differences between humans and their alleged ancestors somehow seems wrong to me. Now, how do we know the human and chimp mutation rates? We have to know that before we can calculate the substitution rate, correct? Please tell me we don't know it by looking at the differences between humans and chimpsMung_{November 11, 2012
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Using Numerical Simulation to Test the Validity of Neo-Darwinian Theory - 2008 Abstract: Evolutionary genetic theory has a series of apparent “fatal flaws” which are well known to population geneticists, but which have not been effectively communicated to other scientists or the public. These fatal flaws have been recognized by leaders in the field for many decades—based upon logic and mathematical formulations. However population geneticists have generally been very reluctant to openly acknowledge these theoretical problems, and a cloud of confusion has come to surround each issue. Numerical simulation provides a definitive tool for empirically testing the reality of these fatal flaws and can resolve the confusion. The program Mendel’s Accountant (Mendel) was developed for this purpose, and it is the first biologically-realistic forward-time population genetics numerical simulation program. This new program is a powerful research and teaching tool. When any reasonable set of biological parameters are used, Mendel provides overwhelming empirical evidence that all of the “fatal flaws” inherent in evolutionary genetic theory are real. This leaves evolutionary genetic theory effectively falsified—with a degree of certainty which should satisfy any reasonable and open-minded person. http://www.icr.org/i/pdf/technical/Using-Numerical-Simulation-to-Test-the-Validity-of-Neo-Darwinian-Theory.pdf Here is a short sweet overview of Mendel's Accountant: When macro-evolution takes a final, it gets an "F" - Using Numerical Simulation to Test the Validity of Neo-Darwinian Theory (Mendel's Accountant) Excerpt of Conclusion: This (computer) program (Mendel’s Accountant) is a powerful teaching and research tool. It reveals that all of the traditional theoretical problems that have been raised about evolutionary genetic theory are in fact very real and are empirically verifiable in a scientifically rigorous manner. As a consequence, evolutionary genetic theory now has no theoretical support—it is an indefensible scientific model. Rigorous analysis of evolutionary genetic theory consistently indicates that the entire enterprise is actually bankrupt. http://radaractive.blogspot.com/2010/06/god-versus-darwin-when-macro-evolution.html Oxford University Admits Darwinism's Shaky Math Foundation - May 2011 Excerpt: However, mathematical population geneticists mainly deny that natural selection leads to optimization of any useful kind. This fifty-year old schism is intellectually damaging in itself, and has prevented improvements in our concept of what fitness is. - On a 2011 Job Description for a Mathematician, at Oxford, to 'fix' the persistent mathematical problems with neo-Darwinism within two years. http://www.evolutionnews.org/2011/05/oxford_university_admits_darwi046351.html The next evolutionary synthesis: from Lamarck and Darwin to genomic variation and systems biology Excerpt: If more than about three genes (nature unspecified) underpin a phenotype, the mathematics of population genetics, while qualitatively analyzable, requires too many unknown parameters to make quantitatively testable predictions [6]. The inadequacy of this approach is demonstrated by illustrations of the molecular pathways that generates traits [7]: the network underpinning something as simple as growth may have forty or fifty participating proteins whose production involves perhaps twice as many DNA sequences, if one includes enhancers, splice variants etc. Theoretical genetics simply cannot handle this level of complexity, let alone analyse the effects of mutation.. http://www.biosignaling.com/content/pdf/1478-811X-9-30.pdfbornagain77_{November 11, 2012
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wd400- Neither YOU nor anyone else knows if the equations are valid. So why do you insist on using them?Joe_{November 11, 2012
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@wd400
The exact probability that, say, the kreb cycle could evolve is completely unknowable. Evolution is a contingent process, and a chancy one at that. I’m very happy to say a random walk through the space of all sequences would never find a kreps cycle, or cellular division or whatever else you want to name. That’s because the parts of sequence space that are biologically viable are certainly very small. But selection can navigate them, we’ve seen that in the field and in the lab (and, in fact, in computational models).
I admit the exact probability is probably unknowable, but we need to start from what we do know and not rely on what may or may not exist out there to bolster our faith. We know what does work and we know that a heck of a lot of other combinations do not work. These things are delicately balanced and fantastically designed. I think that just saying "Well, there might be other combinations that also would have worked." is a cop out. Everything we know would seem to mitigate against that. It seems like a desperate attempt to try and nullify the obvious improbability problem that is staring us in the face. "But selection can navigate them..." That sir, is a statement of faith. you are assuming that there exists an incremental step from one thing to the next in which each successive step would provide enough of a benefit to the organism for selection to kick in. But we don't know this. If such a path does indeed exist, then we would have to admit that it is possible, but even then being possible does not mean it happened like that. Possible means "maybe" not "certainty". We do know that selection misses slightly negative changes and recessive genes that can later cause problems. So how could it select for slightly positive and recessive genes that might later on be beneficial to have?tjguy_{November 11, 2012
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@wd400 "I just went to random.org and picked a number between 1 and 100000000. I got 22166740. That’s a 1 in hundred million chance! I didn’t pre-specify it or anything. But it matters, because 22166740 is there." wd, you don't see any fallacy here with this reasoning? In this case, you were guaranteed to get an outcome between your numbers, but with evolution, there is no such guarantee there will be any outcome. Life didn't have to evolve, but in your example, you were guaranteed to get a number and for your purposes, any number would do. Let's say you had to have this particular number in order to succeed in the evolutionary story. Then what are the chances of getting the desired number? Fantastically small! So two problems with this illustration. You guaranteed yourself an outcome and it was not specified. Any outcome was fine for your purposes.tjguy_{November 11, 2012
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@wd400 "There are some very interesting theories as to how the “slakcening” of slection, which mainly acts to keep things as they are on a molecular level, might facilitate the evolution of complexity." How are you using the word theory here? In the scientific sense such as the theory of gravity or in the non scientific sense of "idea" or "speculation?" Creationists don't hate these types of ideas. To be honest, we laugh at them. It is amazing what evolutionists are willing to consider to try and save their ideas and desired beliefs.tjguy_{November 11, 2012
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FWIW, here's how I try to teach this to undergrads. For any gene in a population, you can trace back a lineage. Eventually all those lineages will coalesce to a shared common ancestor. If we disregard selection then the particular variant that becomes the common ancestor of the whole population is 'chosen' at random. So the probability that it's a gene called "A" is just the freqency of "A" over the population size (N). Shorter version: the probability that an allele (a gene variant) gets fixed is equal to the frequency of the allele. How often to new mutants get fixed? For that we need the rate at which they enter the population, and the proportion of them make it to fixation. The mutation rate is obviosly the individual mutation rate (u) * the population size = Nu. When a new mutation enters the population it is fairly obviously at frequency 1/N. So the substituion rate (k) = N * u * 1/u = u. (as I say, this is in every intro to pop. gen. course, you can verify it easily enough)wd400_{November 11, 2012
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This is unbelievable. The number I calculated really is the expected number of fixed differences, in the population genetics, spreading through the population and taking over, sense. If you want to be a critic of evolutionary theory you might start by learning something about it.wd400_{November 11, 2012
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wd400 @72: Nobody is talking about the total number of mutations in the entire population. The calculation is talking about getting from point A organism at year 0 to point B organism 6M years later. Over 6M years, we can use your 15/years/generation = 400,000 generations *65 mutations per generation, gives the 28M number you indicated. That is perfectly clear. That is the total number of mutations that have arisen across the generations in the line leading to this particular individual. What is not clear is why you are calling these "fixed" mutations. That is not at all what we are talking about. We're talking about a particular mutation becoming fixed throughout the population. I thought you agreed with this, as you said "the time to fix depends on selection pressure." I am using "fixed" in the sense of population genetics, in which the new mutation spreads through the entire population. I'm now wondering if you are using the word the same way. Certainly there are not 65 new mutations that become fixed in the entire human population every generation. There are roughly 65 mutations per generation from one set of parents to a particular child. That has nothing to do with said mutations becoming fixed in the population. When you put out your calculation at the start of this thread I agreed that it was a reasonable number, based on the number of mutations to get to a particular individual. However, if you are now claiming that in each generation we get 65 mutations "fixed" throughout the population (in the sense the term is used in population genetics), then I will certainly have to disagree with the numbers. Bottom line: getting a certain number of mutations (a) in a single line leading to a particular individual, is vastly different from (b) getting those mutations to become fixed in the population.Eric Anderson_{November 10, 2012
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You still don't get this first calculation! That's the expected number of fixed differences, not the aggregate number of mutations (which would be much bigger,65 per individual * 10e4 individuals per generation * 45000 generations giving ~300 billion!) As for the other half, I think it's very likely Gauger is mis-remembering the "waiting for two mutations" paper linked above. Otherwise it's very hard to make sense of her statement.wd400_{November 10, 2012
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wd400:
This is ridiculous.
Well, I'll have to let NIH know! Anyway, I'm not that exercised about definitions. Gauger was talking about "one mutation in a DNA binding site." Whether we want to think about point mutations, insertions, deletions, substitutions, whatever, the principle is the same.
In pop. gen. substitution means the replacement of an existing allele by a new one. That is, fixed differences between humans and chimps. Of course lots of differences have taken over the human population – the first calculation I gave here shows that more than 50 million would be expected to be fixed in the ~6 million year window!
Your numbers showed that a certain number of mutations could occur, in aggregate, over 6M years down a lineage line. Agreed. That is not at issue. However, having a mutation show up is very different from having the mutation become fixed across the population. (BTW, the 65 mutations/generation was based primarily on point mutations, but, again, the principle holds for other kinds of mutations, so we don't need to get hung up on that.)
I’ve shown the mean waiting time for a super-specified mutation is ~ 10 000 generations. The time it would then take to fix depends on selection pressure.
Let me make sure I'm understanding you. It sounds like you are saying that Gauger is off by a factor of 40 (plus or minus) in terms of how long it will take for a pre-specified mutation to show up in the population? (10,000 generations x 15 years = 150,000 years; 150,000 x 40 = 6M years) Would you have a different view if you understood Gauger's statement to be referring to the time necessary for the mutation to get fixed in the population (as you mention, and as I agree, it would be dependent significantly on the relevant selection pressure)?Eric Anderson_{November 10, 2012
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Eric and wd400- The word "substitution" wrt biology is used to mean both a mutation and fixation
the first calculation I gave here shows that more than 50 million would be expected to be fixed in the ~6 million year window!
But no one can confirm/ verify that your calculation is correct, which means it is meaningless.Joe_{November 10, 2012
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Eric. This is ridiculous. In pop. gen. substitution means the replacement of an existing allele by a new one. That is, fixed differences between humans and chimps. Of course lots of differences have taken over the human population - the first calculation I gave here shows that more than 50 million would be expected to be fixed in the ~6 million year window! The simplest reading of : “. . . [given the population sizes and reproduction rates] it takes 6 million for 1 mutation in a DNA binding site to arise would the time it takes for a mutation to turn up. I've shown the mean waiting time for a super-specified mutation is ~ 10 000 generations. The time it would then take to fix depends on selection pressure.wd400_{November 10, 2012
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wd400 @64:
You seem to still not understand the difference between mutation and substituion.
Hmmm . . . This is how the NIH's National Human Genome Research Institute website defines a "substitution":
"Substitution is a type of mutation where one base pair is replaced by a different base pair. The term also refers to the replacement of one amino acid in a protein with a different amino acid."
Anyway, moving on . . . ----
Now you think Gauger is saying it will take millions of years to get one mutation to arise she is just bizarrely wrong.
She is not saying it takes that long for the mutation to arise, and you know it. She is saying it will take that long for the mutation to become fixed in a population. And by fixed in a population, she isn't talking about some random person today having the mutation (which is how you seem to be approaching your calculation). She is talking about the population getting to the point where the mutational change is seen in essentially all organisms in the population. I presume you acknowledge that there are changes in the human-chimp genome of that category (namely, seen in all humans and not in chimps), so they must have become fixed in the entire population over time. We're not just talking about adding up a bunch of random changes in multiple (human) lineages over time. Whatever key differences exist between humans and chimps must have become fixed in the entire human population at some point.
But, again, this paper has some very narrow assumptions and, most importantly, it starts by prespecifying a particular combination of mutations and asking how likely that combination is to arise. But evolution is a contingent process, there was never a pre-specification for evolutoin to aim at. Is that clear enough.
Oh, it is quite clear. And your statement is now Exhibit B in demonstrating precisely what I was saying about the Darwinist mindset way back in #47. Rather than repeating what I wrote, I will therefore just refer everyone back to #47.Eric Anderson_{November 10, 2012
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wd400:
The calculations above show you you’d expect 50 million fixed differences in SNPS (in the ballpark of the observed data) over 6 million years.
The equations that have never been verified to reflect reality? Why should anyone care about them?
That’s because the substituion rate is expected to equal the per individual mutation rate under neutrality.
Why? Has anyone ever confirmed that? Ya see wd400, when you use equations that no one knows if they work or not, there is a problem. So perhaps you should focus on that but I am sure that you won't.Joe_{November 10, 2012
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There is not even the slightest possibility that you could be right. Understand? No, but then you haven't yet explained.... care to?wd400_{November 10, 2012
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I love the you don't understand argument because wd400 you do not understand. There is not even the slightest possibility that you could be right. Understand?Andre_{November 9, 2012
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This really shouldn't be this hard. First. You seem to still not understand the difference between mutation and substituion. The calculations above show you you'd expect 50 million fixed differences in SNPS (in the ballpark of the observed data) over 6 million years. That's because the substituion rate is expected to equal the per individual mutation rate under neutrality. So the idea that somehow you'd wait 6 million years for one fixation (with selection!) is obviously woefully wrong. Now you think Gauger is saying it will take millions of years to get one mutation to arise she is just bizarrely wrong. Even if you specified to muation down to a single site the population mutation rate is Effective population size * per-site mutation rate. Back of an envelope that's 10e4 * 10e-8 = 10e-4. The expected waiting time for a process like this is from the exponential distribution, giving 10,000 generations as teh waiting time for any specific mutation. What Gauger is persumably actually talking about is co-ordinated mutations (http://www.genetics.org/content/180/3/1501.full). But, again, this paper has some very narrow assumptions and, most importantly, it starts by prespecifying a particular combination of mutations and asking how likely that combination is to arise. But evolution is a contingent process, there was never a pre-specification for evolutoin to aim at. Is that clear enough.wd400_{November 9, 2012
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