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Alzheimer disease evolved alongside human intelligence, says Nature article

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Here.

In this way, the researchers looked back at selection events that occurred up to 500,000 years ago, revealing the evolutionary forces that shaped the dawn of modern humans, thought to be around 200,000 years ago. Most previous methods for uncovering such changes reach back only about 30,000 years, says Stephen Schaffner, a computational biologist at the Broad Institute in Cambridge, Massachusetts.

The analytical approach that Tang’s team used is promising, he adds. “It’s treating all kinds of selection in a uniform framework, and it’s also treating different eras of selection in a more or less uniform way.” But Schaffner says that further research is needed to confirm that the method is broadly applicable.

Still, even the most powerful genomic-analysis methods can be limited by the vagaries of history. Asian and European people descended from a small number of people who left Africa around 60,000 years ago …

The article is a classic in that it is replete with Darwinbabble which gets more annoying as its gets more obviously useless.

For one thing, Alzheimer is probably mainly noticed in humans. If an alpha wolf or bull moose gets a little ditzy, he is probably just replaced by an ambitious subordinate.

That’s not quite what happens when we must, often with considerable reluctance, accept that a loved one is experiencing long term brain challenges. For example, a typical checklist might include:

Moderate Alzheimer’s is typically the longest stage and can last for many years. As the disease progresses, the person with Alzheimer’s will require a greater level of care.

You may notice the person with Alzheimer’s confusing words, getting frustrated or angry, or acting in unexpected ways, such as refusing to bathe. Damage to nerve cells in the brain can make it difficult to express thoughts and perform routine tasks.

At this point, symptoms will be noticeable to others and may include:

– Forgetfulness of events or about one’s own personal history

– Feeling moody or withdrawn, especially in socially or mentally challenging situations

– Being unable to recall their own address or telephone number or the high school or college from which they graduated

One must already be a human being to have these kinds of problems. Where is the evolution, exactly?

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Comments
"It all comes down to one parameter, but the problem is there is a lot of biology in this one parameter. Mutation is in there drift is in there and selection is in there." - Michael Lynch 27:40ff https://www.youtube.com/watch?v=GKo--DnOPwYMung
June 12, 2015
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Meanwhile, back in the real world: The Drift BarrierMung
June 12, 2015
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"Computational Biologists" building models to show evolution is true. What a waste of resources. It would not be as bad if a study fraught with errors gave some benefit - but this AD study does not even stumble on to anything useful.ppolish
May 25, 2015
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Can you just answer the question SA?wd400
May 25, 2015
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Probability Sample built from data of three Neanderthals. Random? What a joke this paper is. Probably peer reviewed.ppolish
May 25, 2015
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wd400 If selection coefficients are random, then you're right. Selection is random and drift is random.Silver Asiatic
May 25, 2015
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LS, If you think Mung had made a "telling" criticism, then can you explain that criticism on your own words? I genuinely can't find anything coherent, let alone telling, in his/her posts.wd400
May 25, 2015
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SA, Do you seriously think my comment in 25 is wrong? That drawing a sample from a probability distribution is not a type of random sampling?wd400
May 25, 2015
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"Humans get AD because they evolved to be so smart". But Dogs & Cats develop AD. Convergent Evolution. Evolution is so cool. http://www.drsfostersmith.com/pic/article.cfm?articleid=1346 http://vetmedicine.about.com/od/diseasesconditionscat/tp/feline-dementia.htmppolish
May 25, 2015
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LS @32 Agreed. wd400 fell right into it and his illogical response @25 is a perfect example of how empty the theorizing actually is. Larry Moran did the same thing. He can't distinguish between selection and random sampling of non-neutral alleles.Silver Asiatic
May 25, 2015
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News: For one thing, Alzheimer is probably mainly noticed in humans. Good question. Alzheimer's disease causes observable changes in the brain, so it can be studied in animals. See Finch & Austad, Commentary: is Alzheimer's disease uniquely human?, Neurobiology of Aging 2015. Mung: How did they rule out genetic drift? Because the rates of change exceed those expected by the statistics of drift alone. The authors were able to estimate the influence of positive, negative and balancing selection, as well as neutrality, and over how many generations selection was acting.Zachriel
May 25, 2015
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I have to say that the exchange between Mung and Wd400 has been excellent so far. The way Mung has schooled wd400 without wd400 even realising it seems, is an stellar example of how to debate these people. Wd400 tried in vain to use the "you don't know enough and I am not going to tell you!" tactic. When that didn't work, Mung got wd400 to say what the whole problem is in the first place, classic.logically_speaking
May 25, 2015
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Is it drift? Neutral? Selection? Nobody knows but what we do know as an absolute fact, it was not by design. Anything and nothing can do it. By design? Absolutely not!Andre
May 25, 2015
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Is this a prelude to some first year philosophy discussion about the meaning of "force"? If so count me out. If not, it's a force in the same sense, say, erosion is a often described as a force: it's a process that changes the thing on which it acts.wd400
May 24, 2015
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wd400, How is selection a force?phoodoo
May 24, 2015
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Mapou at @13, " This is the kind of crap one can expect from a dirt-did-it theory ducttaped together with stupidity?" One of the best lines I read here.phoodoo
May 24, 2015
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Mung: If the drawing is based only on the selection coefficients as you say, then the sampling is not random wd400: This is simply not true, and seems to be that root of your other errors. I've made no errors. You, otoh, have consistently conflated the neutral theory of evolution with random genetic drift.Mung
May 24, 2015
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The author of the thread is right. I say animals also would have this disease. Likewise the clues in it are the memory problems. It is just a memory problem or rather a triggering problem in the memory from old age . I say this confidently. Nothing to do with selection on man over long times. Its dumb and very poor research even by evolution standards if i may say so. The symtoms are the same if one is drinking booze too much. The same mechanism. I think it can be healed. By the way all this mixing of Communist dictatorship China with the west must mean China is okay morally and politically eh!! Nope. Keep it home folks and it will be better anyways.Robert Byers
May 24, 2015
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If the drawing is based only on the selection coefficients as you say, then the sampling is not random
This is simply not true, and seems to be that root of your other errors.wd400
May 24, 2015
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wd400:
You can’t separate to the two — you draw with probabilities determined by the selection coefficients.
No, you cannot separate the two, and that's my point. The only mechanism you're offering is selection unless the allele is neutral. If the drawing is based only on the selection coefficients as you say, then the sampling is not random. If the sampling is not random then there is no random genetic drift. You are conflating genetic drift with neutral evolution. It may in fact be the case that genetic drift is the only mechanism by which neutral alleles can become fixed, but it does not follow that selection is the only mechanism by which non-neutral alleles can become fixed. But then, you already know this. What I am struggling to understand is why you think alleles which are not selectively neutral cannot be fixed by random genetic drift [as well as by selection]. I actually don't think you think this, but you keep arguing as if you do. wd400:
To a first approximation, selection will dominate when twice the (effective) population size times the selection coefficient (2.Ne.s) is greater than 1.
Else what? Random genetic drift will dominate and neutral alleles will be fixed at a greater frequency than non-neutral alleles? Or at this point is the selection coefficient pretty much irrelevant.Mung
May 24, 2015
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You can't separate to the two -- you draw with probabilities determined by the selection coefficients. For moderately large populations, if the difference in fitnesses if large, then the randomness of sampling will have little effect on the alleles that make it through. If all alleles have the same fitness then the random sampling is the only thing deciding which alleles make it.wd400
May 24, 2015
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wd400, thank you. Let me attempt a different approach. Say I want to create a model of evolutionary mechanisms. For now I'll stick with genetic drift and selection. I create an initial population of organisms and assign to each some selective value. Just for grins and because I don't really know what the hack i'm doing I will assign to most of them a neutral or nearly neutral selective value. Now I want to create from this population the members of the next generation. How do I decide the composition of the next generation? Should I perform the random sampling first or look at the selective value first?Mung
May 24, 2015
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I can't diagnose all of your misunderstanding here, so I'll just encourage you to learn som more. Perhaps start by thinking about the question you first asked -- how can you tell the difference between drift and selection, and how selection relates to neutrality.
If an allele becomes fixed (or lost) you can’t from that infer it was fixed (or lost) because of selection.
Correct. Nothing in this method tries to do that.
Genetic drift does not have a preference for neutral alleles. Isn’t that true?
I don't know what you mean by preference, but drift is not a strong force for alleles with large fitness differences. (That is, the fate of all allele depends very little on random sampling when selection coefficients are large)
I asked Dr. Moran at what population size is genetic drift likely to swamp selection. Still waiting for an answer.
To a first approximation, selection will dominate when twice the (effective) population size times the selection coefficient (2.Ne.s) is greater than 1.wd400
May 24, 2015
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wd400:
Under neutrality all you have is random sampling (drift). If that pattern can’t easily be explained by neutral, random sampling only, model then it’s likely non-random-sampling (selection) happened. Yes?
Why would you model all genetic drift as neutral evolution when that's not the way genetic drift works? What justifies the assumption? If an allele becomes fixed (or lost) you can't from that infer it was fixed (or lost) because of selection. Genetic drift does not have a preference for neutral alleles. Isn't that true? I asked Dr. Moran at what population size is genetic drift likely to swamp selection. Still waiting for an answer.Mung
May 24, 2015
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As I said in my first comment on this,
Because we know what that distribution should look like under neutrality, you make a statistical test for non-neutral patterns like selection.
Under neutrality all you have is random sampling (drift). If that pattern can't easily be explained by neutral, random sampling only, model then it's likely non-random-sampling (selection) happened. Yes?wd400
May 24, 2015
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wd400:
It’s really not my job to teach you intro pop gen.
Indeed it isn't. But you claimed one of is confused and I've seen no evidence that I was the one confused. If I am the one confused I thought I'd try to learn why. wd400:
Under neutrality ... the only thing changing allele frequencies is drift.
So what? I've said repeatedly now that you are conflating genetic drift with neutrality and you're doing nothing to change that. Genetic drift is due to [caused by] random sampling, and it's not checking to see whether some allele is neutral or not before taking the sample. Of course, you know this, or should. wd400:
When you exclude neutrality you are effectively saying “could this result have arisen by drift alone”. If the answer is ‘no’ then you have evidence of some other force, in this cases selection.
Tell me how one can distinguish between selection [non random sampling] as the cause and genetic drift [random sampling] as the cause when the effect is the same. That's what I want to know.Mung
May 24, 2015
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"It’s really not my job to teach you intro pop gen. But here’s the brief summary." Here's a bit more summary with the ugly pieces included that wd400 left out: As to Neutral Evolution:
Kimura (1968) developed the idea of “Neutral Evolution”. If “Haldane’s Dilemma” is correct, the majority of DNA must be non-functional.
Neutral theory was not developed because of any empirical observation, but was developed because it was forced upon Darwinism by the mathematics. (i.e. neutral theory is actually the result of a theoretical failure of Darwinism within mathematics!)
Haldane’s Dilemma Excerpt: Haldane was the first to recognize there was a cost to selection which limited what it realistically could be expected to do. He did not fully realize that his thinking would create major problems for evolutionary theory. He calculated that in man it would take 6 million years to fix just 1,000 mutations (assuming 20 years per generation).,,, Man and chimp differ by at least 150 million nucleotides representing at least 40 million hypothetical mutations (Britten, 2002). So if man evolved from a chimp-like creature, then during that process there were at least 20 million mutations fixed within the human lineage (40 million divided by 2), yet natural selection could only have selected for 1,000 of those. All the rest would have had to been fixed by random drift – creating millions of nearly-neutral deleterious mutations. This would not just have made us inferior to our chimp-like ancestors – it surely would have killed us. Since Haldane’s dilemma there have been a number of efforts to sweep the problem under the rug, but the problem is still exactly the same. ReMine (1993, 2005) has extensively reviewed the problem, and has analyzed it using an entirely different mathematical formulation – but has obtained identical results. John Sanford PhD. – “Genetic Entropy and The Mystery of the Genome” – pg. 159-160 Walter ReMine on Haldane’s Dilemma – interview http://kgov.com/Walter-ReMine-on-Haldanes-Dilemma Kimura’s Quandary Excerpt: Kimura realized that Haldane was correct,,, He developed his neutral theory in response to this overwhelming evolutionary problem. Paradoxically, his theory led him to believe that most mutations are unselectable, and therefore,,, most ‘evolution’ must be independent of selection! Because he was totally committed to the primary axiom (neo-Darwinism), Kimura apparently never considered his cost arguments could most rationally be used to argue against the Axiom’s (neo-Darwinism’s) very validity. John Sanford PhD. – “Genetic Entropy and The Mystery of the Genome” – pg. 161 – 162
A graph featuring ‘Kimura’s Distribution’ being ‘properly used’ is shown in the following video:
Evolution Vs Genetic Entropy – Andy McIntosh – video https://vimeo.com/91162565
John Sanford has indeed backed up his claim that the mathematics of population genetics could be used to argue against the very validity of Darwinism.
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 Using Numerical Simulation to Better Understand Fixation Rates, and Establishment of a New Principle – “Haldane’s Ratchet” – Christopher L. Rupe and John C. Sanford – 2013 Excerpt: We then perform large-scale experiments to examine the feasibility of the ape-to-man scenario over a six million year period. We analyze neutral and beneficial fixations separately (realistic rates of deleterious mutations could not be studied in deep time due to extinction). Using realistic parameter settings we only observe a few hundred selection-induced beneficial fixations after 300,000 generations (6 million years). Even when using highly optimal parameter settings (i.e., favorable for fixation of beneficials), we only see a few thousand selection-induced fixations. This is significant because the ape-to-man scenario requires tens of millions of selective nucleotide substitutions in the human lineage. Our empirically-determined rates of beneficial fixation are in general agreement with the fixation rate estimates derived by Haldane and ReMine using their mathematical analyses. We have therefore independently demonstrated that the findings of Haldane and ReMine are for the most part correct, and that the fundamental evolutionary problem historically known as “Haldane’s Dilemma” is very real. Previous analyses have focused exclusively on beneficial mutations. When deleterious mutations were included in our simulations, using a realistic ratio of beneficial to deleterious mutation rate, deleterious fixations vastly outnumbered beneficial fixations. Because of this, the net effect of mutation fixation should clearly create a ratchet-type mechanism which should cause continuous loss of information and decline in the size of the functional genome. We name this phenomenon “Haldane’s Ratchet”. http://media.wix.com/ugd/a704d4_47bcf08eda0e4926a44a8ac9cbfa9c20.pdf
Here is a recent article, not associated with Dr. Sanford, that also found a insurmountable barrier in the theoretical framework of Darwinism:
Neo-Darwinism’s Catch-22: Before Evolving New Features, Organisms Would Be Swamped by Genetic Junk – Casey Luskin – April 10, 2015 Excerpt: A new peer-reviewed paper in the journal Complexity presents a computational model of evolution which shows that evolving new biological structures may be deterred by an unavoidable catch-22 problem.,,, This is a bit complex — let’s go over it again. Darwinian evolution either (1) produces nothing new, or (2) it’s destined to produce boatloads of deadly junk. In the case of (2), the reward for trying new things is high compared to the cost of building new structures. But in order for the ratio to be high enough for complexity to increase, the cost of building new things must be negligible. Novelties proliferate, but the fraction,, that’s vestigial grows, and the organism is eventually swamped and overwhelmed by harmful vestigial features. However, if you try to avoid the problem of (2) by making the reward-to-cost ratio lower, as in (1), then nothing new ever evolves. The authors think real biological organisms are closer to position (1). Indeed, study in the field of systems biology increasingly finds that biological systems contain very little junk.,,, per ENV
There are also other strong theoretical and empirical reasons to believe neutral theory is incorrect:
Unexpectedly small effects of mutations in bacteria bring new perspectives – November 2010 Excerpt: Most mutations in the genes of the Salmonella bacterium have a surprisingly small negative impact on bacterial fitness. And this is the case regardless whether they lead to changes in the bacterial proteins or not.,,, using extremely sensitive growth measurements, doctoral candidate Peter Lind showed that most mutations reduced the rate of growth of bacteria by only 0.500 percent. No mutations completely disabled the function of the proteins, and very few had no impact at all. Even more surprising was the fact that mutations that do not change the protein sequence had negative effects similar to those of mutations that led to substitution of amino acids. A possible explanation is that most mutations may have their negative effect by altering mRNA structure, not proteins, as is commonly assumed. http://www.physorg.com/news/2010-11-unexpectedly-small-effects-mutations-bacteria.html “Moreover, there is strong theoretical reasons for believing there is no truly neutral nucleotide positions. By its very existence, a nucleotide position takes up space, affects spacing between other sites, and affects such things as regional nucleotide composition, DNA folding, and nucleosome building. If a nucleotide carries absolutely no (useful) information, it is, by definition, slightly deleterious, as it slows cell replication and wastes energy.,, Therefore, there is no way to change any given site without some biological effect, no matter how subtle.” – John Sanford – Genetic Entropy and The Mystery of The Genome – pg. 21 – Inventor of the ‘Gene Gun’ etc.. etc..
here are some supplemental comments/quips as to neutral theory:
Majestic Ascent: Berlinski on Darwin on Trial – David Berlinski – November 2011 Excerpt: The publication in 1983 of Motoo Kimura’s The Neutral Theory of Molecular Evolution consolidated ideas that Kimura had introduced in the late 1960s. On the molecular level, evolution is entirely stochastic, and if it proceeds at all, it proceeds by drift along a leaves-and-current model. Kimura’s theories left the emergence of complex biological structures an enigma, but they played an important role in the local economy of belief. They allowed biologists to affirm that they welcomed responsible criticism. “A critique of neo-Darwinism,” the Dutch biologist Gert Korthof boasted, “can be incorporated into neo-Darwinism if there is evidence and a good theory, which contributes to the progress of science.” By this standard, if the Archangel Gabriel were to accept personal responsibility for the Cambrian explosion, his views would be widely described as neo-Darwinian. http://www.evolutionnews.org/2011/11/berlinski_on_darwin_on_trial053171.html
With the adoption of the ‘neutral theory’ of evolution by many prominent Darwinists, and the casting under the bus of Natural Selection as a major player in evolution, William J Murray quipped,,,
“One wonders what would have become of evolution had Darwin originally claimed that it was simply the accumulation of random, neutral variations that generated all of the deeply complex, organized, interdependent structures we find in biology? Would we even know his name today? What exactly is Darwin really famous for now? Advancing a really popular, disproven idea (of Natural Selection), along the lines of Luminiferous Aether? Without the erroneous but powerful meme of “survival of the fittest” to act as an opiate for the Victorian intelligentsia and as a rationale for 20th century fascism, how might history have proceeded under the influence of the less vitriolic maxim, “Survival of the Happenstance”?” – William J Murray Here is a Completely Different Way of Doing Science – Cornelius Hunter PhD. – April 2012 Excerpt: But how then could evolution proceed if mutations were just neutral? The idea was that neutral mutations would accrue until finally an earthquake, comet, volcano or some such would cause a major environmental shift which suddenly could make use of all those neutral mutations. Suddenly, those old mutations went from goat-to-hero, providing just the designs that were needed to cope with the new environmental challenge. It was another example of the incredible serendipity that evolutionists call upon. Too good to be true? Not for evolutionists. The neutral theory became quite popular in the literature. The idea that mutations were not brimming with cool innovations but were mostly bad or at best neutral, for some, went from an anathema to orthodoxy. And the idea that those neutral mutations would later magically provide the needed innovations became another evolutionary just-so story, told with conviction as though it was a scientific finding. Another problem with the theory of neutral molecular evolution is that it made even more obvious the awkward question of where these genes came from in the first place. http://darwins-god.blogspot.com/2012/04/here-is-completely-different-way-of.html
as to drift specifically
Ann Gauger on genetic drift – August 2012 Excerpt: The idea that evolution is driven by drift has led to a way of retrospectively estimating past genetic lineages. Called coalescent theory, it is based on one very simple assumption — that the vast majority of mutations are neutral and have no effect on an organism’s survival. (For a review go here.) According to this theory, actual genetic history is presumed not to matter. Our genomes are full of randomly accumulating neutral changes. When generating a genealogy for those changes, their order of appearance doesn’t matter. Trees can be drawn and mutations assigned to them without regard to an evolutionary sequence of genotypes, since genotypes don’t matter. https://uncommondescent.com/evolution/ann-gauger-on-genetic-drift/ Thou Shalt Not Put Evolutionary Theory to a Test – Douglas Axe – July 18, 2012 Excerpt: “For example, McBride criticizes me for not mentioning genetic drift in my discussion of human origins, apparently without realizing that the result of Durrett and Schmidt rules drift out. Each and every specific genetic change needed to produce humans from apes would have to have conferred a significant selective advantage in order for humans to have appeared in the available time (i.e. the mutations cannot be ‘neutral’). Any aspect of the transition that requires two or more mutations to act in combination in order to increase fitness would take way too long (greater than 100 million years). My challenge to McBride, and everyone else who believes the evolutionary story of human origins, is not to provide the list of mutations that did the trick, but rather a list of mutations that can do it. Otherwise they’re in the position of insisting that something is a scientific fact without having the faintest idea how it even could be.” – Doug Axe PhD. per Evolution News and Views Natural Selection Struggles to Fix Advantageous Traits in Populations – Casey Luskin – October 23, 2014 Excerpt: Michael Lynch, an evolutionary biologist at Indiana University,, writes that “random genetic drift can impose a strong barrier to the advancement of molecular refinements by adaptive processes.”2 He notes that the effect of drift is “encouraging the fixation of mildly deleterious mutations and discouraging the promotion of beneficial mutations.”3 Likewise, Eugene Koonin, a leading scientist at the National Institutes of Health, explains that genetic drift leads to “random fixation of neutral or even deleterious changes.”4 http://www.evolutionnews.org/2014/10/natural_selecti_3090571.html
bornagain77
May 24, 2015
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It's really not my job to teach you intro pop gen. But here's the brief summary. Under neutrality (and excluding demographic changes which are handled neatly in this model, and inbreeding which is unlikely to be an issue here) the only thing changing allele frequencies is drift. When you exclude neutrality you are effectively saying "could this result have arisen by drift alone". If the answer is 'no' then you have evidence of some other force, in this cases selection.wd400
May 24, 2015
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From the paper (thx WD400 for the link): "Abundant signals of BS were detected" No kidding. Grab 3 Neanderthals and build a model. Abundant BS sure to be found there. "AD remains arguably a disease unique to humans. Not observed in chimps" Why are evolutionists so obsessed with chimps. How many chimps have been observed? Dogs & Cats suffer dementia. AD probably. Look, AD is based on some Design Rule. Find that Design Rule fcol. "AD due to NS" what a useless pile of BS. Useless & BS.ppolish
May 24, 2015
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wd400:
If some observed data is unlikely to arise under neutrality (i.e. by drift alone) then it is likely that selection was involved in generating that data. Isn’t it?
Like I said, you're confusing neutrality with drift. Surely you know better, so why pretend you don't? There is nothing at all in the definition of genetic drift that requires it to act only on neutral alleles. http://en.wikipedia.org/wiki/Genetic_drift http://en.wikipedia.org/wiki/Population_genetics#Genetic_drift Added in Edit: How does random sampling know to sample only neutral alleles? If I am wrong, please explain why.Mung
May 24, 2015
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