Haldane's Dilemma

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    SCOTT L. PAGE
    The following papers:J. C. Fay, G. J. Wyckoff and C.-I. Wu: Positive and Negative Selection on the Human Genome, Genetics 158, 1227-1234. 2001.andSexual Recombination and the
    Power of Natural Selection
    William R. Rice* and Adam K. Chippindale
    2001 Science 294:555-559
    severely impact the various claims of creationists who insist that because of 'Haldane's dilemma', among other things, human evolution from an ape-like ancestor is impossible.This 'conclusion' is premised primarily on personal opinions, for there is, at present, no information at all regarding the numbers of fixed beneficial mutations required to explain various adaptations and traits in extant organisms.Nonetheless, the argument regarding the human question goes something like this:According to an extrapolation of Haldane's 1957 paper, no more than 1667 fixed, beneficial mutations could accrue in the lineage leading to humans from an ape-like ancestor.1667 is too few to account for this (unsupported assertion), therefore, humans must not have evolved at all.According to the first paper mentioned, the number is off - way off. We cannot blame Haldane - he was working more than a decade before and sequence data was available to him.

    This paper demonstrates that there have been approximately one beneficial allele substitution every 200 years since the split between Old and New world primates some 30 million years ago.This amounts to 150,000 in 30 million years. The estimated split between the lineage leading to humans from that leading to chimps is around 5-6 million years ago.We'll go with 5. That allows for some 25,000. That is 14 times what was allowed under Haldane's model.Considering the fact that HGP analysis and others put the total gene number in the human genome at between 30 and 60,000, and if we consider that each of these genes may be influenced by at least one regulatory region, 25,000 substitutions - by anyone's standards - should be seen as more than enough to acocunt for the differences.Of course, since it is a fact that it has not been shown that 1667 fbms is too few, I am still not convinced that it cannot be explained by the lower number.I suppose it all rests on one's point of view, a! nd whether or not one is willing to accommodate new discoveries into their lexicon.From the second paper, emphases mine:"Our results experimentally verify a counteracting advantage of recombining compared to clonal lineages: reduced accumulation of harmful mutations and increased accumulation of beneficial mutations. The magnitude of this benefit will accrue over geological timeand promote the superior persistence of recombining lineages at both the

    level of species within communities (clonal versus sexual species) and genes within chromosomes (nonrecombining Y-linked versus recombining X-linked genes)."I don't think that needs any more explanation.Comments appreciated.

    [Administrator: this was edited to remove invalid code and replace with bold to show where the author wished emphasis.]

    [ January 24, 2002: Message edited by: Administrator ]
     
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    HELEN

    Hi Scott,
    I have a couple of problems with some of what you wrote. First of all
    you said simply that we currently have “no information at all regarding
    the numbers of fixed beneficial mutations required to explain various
    adaptations and traits in extant organisms.” Then, at the end, you said
    that 25,000 would be more than enough to account for the difference.
    You also said that 1667 is not known to be too few. That’s quite a
    range! There’s evidently an awful lot we don’t know!

    But, actually, that is not a problem. I cheerfully admit all kinds of
    ignorance. But here is something that is evidently pretty close to true
    – that there are approximately 1000 expressed negative mutations per any
    given possibly beneficial mutation. That means, given your lowest
    number of 1667, that during the time they were accumulating, 1,667,000
    negative mutations also occurred.

    Now I know that many of these are lethal and the individuals would die,
    possibly even before birth. I don’t know the ratio of lethal to simply
    deleterious mutations, but let’s go 1:1 and eliminate half of those
    mutations from the breeding population. That leaves us with 833,500
    expressed deleterious mutations during that time.

    As I understand it, if there is one or more deleterious mutations per
    generation then that population is on an irreversible downhill slide to
    extinction. I believe this is called error catastrophe.

    So in order to collect 1667 beneficial mutations, none of which can be
    lost due to accidental death and all of which must not only be
    heritable, but provide some kind of advantage towards natural selection,
    we must accommodate 833,500 negative mutations.

    Now I have a problem here – we are considering only the time from the
    supposed ape-man split, right? Were there then no deleterious mutations
    passed down to us from our supposed animal ancestors who had been around
    in one form or another for a few billion years? Did the slate somehow
    miraculously start clean at the time of the proposed ape-man split?

    OK, let’s suppose it did. Let’s take a human generation time of 12
    years – quite young for humans today but about two years past what an ape
    generation time is considered to be.

    12 x 833,500 = 10,002,000 years

    And that is at the rate of error catastrophe. It has to be a longer
    time than that. But you said the split was at 5-6 million years ago.

    Or let’s look at it another way. One beneficial substitution every 200
    years. OK. That means in that amount of time there will be about 500
    non-lethal deleterious mutations of one kind or another – and these are
    just the expressed mutations.

    That is WAY past error catastrophe.

    I have made three suppositions above. The first is that there are
    approximately 1000 expressed deleterious mutations per any given
    expressed beneficial mutation. The second is that about half the
    deleterious mutations are lethal before the individuals involved can
    breed. The third is that error catastrophe happens at least at the
    appearance of one deleterious heritable mutation a generation, if not a
    little less. Am I off on those? If not, your figures and that article
    are of no help to evolution at all that I can see.

    I think there are some other major problems, too, with some of what you
    proposed there, but let’s stick with this and see where it leads for
    now.

    Helen

    [ February 01, 2002: Message edited by: Administrator ]
     
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    SCOTT L.PAGE

    <BLOCKQUOTE>quote:</font><HR>I have a couple of problems with some of what you wrote. First of all
    you said simply that we currently have “no information at all regarding
    the numbers of fixed beneficial mutations required to explain various
    adaptations and traits in extant organisms.” Then, at the end, you said
    that 25,000 would be more than enough to account for the difference.
    You also said that 1667 is not known to betoo few. That’s quite a
    range! There’s evidently an awful lot we don’t know! <HR></BLOCKQUOTE>


    Hi Helen,
    That is correct. We– you, me, ReMine, anyone – do not know exactly how many beneficial mutations must have been fixed to account for the evolution of humans from ape-like ancestors. We also do not know exactly what the ancestor was. Without this knowledge, making explicit statements on just how many is too few is an exercise in sophism.
    I do not think 1667 is too few, and there is no actual evidence that it is. I readily admit that my position has no direct supporting evidence, but there is circumstantial evidence. Of course, ReMine presents none. I have his book in front of me right now, and his evidence that 1667 is too few?
    Well, he just says so. That is not evidence. That is pure speculation. I do not think 1667 is too few because I know – and there is evidence to support it – that minor mutations in certain genes can have profound phenotypic effects. A single point mutation, for example, in the gene encoding the FGF-3 receptor – a gene not even directly involved in developmental timing or expression – causes achondroplasia, a major phenotypic change.
    The new evidence I refer to shows that upwards of 25,000 beneficial mutations could have been fixed in the allotted time, so the ‘problem’ grows even smaller. Could you provide a list of 25,000 features that distinguish humans from the ape-like ancestor along with the evidence that each feature you describe requires its own allelic variation/origin to account for it? If not, then your argument continues to lose ground.


    <BLOCKQUOTE>quote:</font><HR>But, actually, that is not a problem. I cheerfully admit all kinds of
    ignorance. But here is something that is evidently pretty close to true
    – that there are approximately 1000 expressed negative mutations per any
    given possibly beneficial mutation. That means, given your lowest
    number of 1667, that during the time they were accumulating, 1,667,000
    negative mutations also occurred. <HR></BLOCKQUOTE>


    References please. In addition, I suggest that you re-read the second citation.


    <BLOCKQUOTE>quote:</font><HR>Now I know that many of these are lethal and the individuals would die,
    possibly even before birth. I don’t know the ratio of lethal to simply
    deleterious mutations, but let’s go 1:1 and eliminate half of those
    mutations from the breeding population. That leaves us with 833,500
    expressed deleterious mutations during that time.

    As I understand it, if there is one or more deleterious mutations per
    generation then that population is on an irreversible downhill slide to
    extinction. I believe this is called error catastrophe. <HR></BLOCKQUOTE>

    Error catastrophe is a purely theoretical condition.

    “To this day, there is no experimental evidence that error catastrophe exists.It is totally theoretical", he [Professor Lowenstein] admits.” http://www.wellcome.ac.uk/en/1/biosfgunkinfshwrep98low.html

    Lowenstein is one of the key researchers into the alleged phenomenon, one that ReMine cites in his book. When I presented this to ReMine in an email exchange, he, of course, claimed that I was ‘misrepresenting him.’

    Sexual recombination accelerates the rate at which harmful mutations are removed and the rate at which beneficial ones are accumulated. Please read the second paper I cite.


    <BLOCKQUOTE>quote:</font><HR>So in order to collect 1667 beneficial mutations, none of which can be
    lost due to accidental death and all of which must not only be
    heritable, but provide some kind of advantage towards natural selection,
    we must accommodate 833,500 negative mutations. <HR></BLOCKQUOTE>


    Incorrect. This is one of the shortcomings of relying solely on mathematical models rather than incorporating actual data into your scenarios.

    <BLOCKQUOTE>quote:</font><HR>Now I have a problem here – we are considering only the time from the
    supposed ape-man split, right? Werethere then no deleterious mutations
    passed down to us from our supposed animal ancestors who had been around
    in one form or another for a few billion years? Did the slate somehow
    miraculously start clean at the time of the proposed ape-man split? <HR></BLOCKQUOTE>


    I will let you continue…


    <BLOCKQUOTE>quote:</font><HR>OK, let’s suppose it did. Let’s take a human generation time of 12
    years – quite young for humans today but about two years past what anape
    generation time is considered to be.

    12 x 833,500 = 10,002,000 years

    And that is at the rate of error catastrophe. It has to be a longer
    time than that. But you said the split was at 5-6 million years ago. <HR></BLOCKQUOTE>


    What is the “rate of error catastrophe”? Please provide a reference for this so that I can see it for myself. Of course, this all neglects the important papers I provided citations for.


    <BLOCKQUOTE>quote:</font><HR>Or let’s look at it another way. One beneficial substitution every 200
    years. OK. That means in that amount of time there will be about 500
    non-lethal deleterious mutations of one kind or another – and these are
    just the expressed mutations.

    That is WAY past error catastrophe. <HR></BLOCKQUOTE>

    Other than your repeated assertion of your opinion, what is the evidence that supports your position? If you cannot explain what, exactly, error catastrophe is, how can you define its limits?


    <BLOCKQUOTE>quote:</font><HR>I have made three suppositions above. The first is that there are
    approximately 1000 expressed deleterious mutations per any given
    expressed beneficial mutation. The second is that about half the
    deleterious mutations are lethal before the individuals involved can
    breed. The third is that error catastrophe happens at least at the
    appearance of one deleterious heritable mutation a generation, if not a
    little less. Am I off on those? If not, your figures and that article
    are of no help to evolution at all that I can see.<HR></BLOCKQUOTE>

    As you admit that you made suppositions, I see little reason to seriously consider them. If,perhaps, you could provide documentation supporting your numbers – as I did –then your suppositions would merit discussion (of course, then they wouldn’t BE suppositions!). But, for the sake of dialogue:

    Suppostion one – 1000:1 deleterious to beneficial. An accumulation of deleterious mutations eventually leads to genetic death. And if these deleterious mutations are removed from a population via other means(accidental death, no reproduction of the individual, etc.), then your supposition one is reduced in its import.

    Supposition two – half of the deleterious mutations are lethal prior to reproduction.

    Thank you – you just removed half of the problematic mutations for me.

    Supposition three - error catastrophe happens at least at the appearance of one deleterious heritable mutation a generation, if not a little less.

    You provide no source documentation for this at all, so I have little confidence in its accuracy. If you can provide some citations – or one, even – in which empirical data is incorporated and the numbers borne out – then I will have to give it some thought. Until then, I see no reason to consider your suppositions as a serious rebuttal.


    <BLOCKQUOTE>quote:</font><HR>I think there are some other major problems, too, with some of what you
    proposed there, but let’s stick with this and see where it leads for
    now. <HR></BLOCKQUOTE>

    The only major problems are for Walter ReMine’s use of Haldane’s dilemma as an ‘evolution stopper.’

    I provided citations for publications that do not rely on purely hypothetical mathematical models, but instead use actual experimentation and actual genetic analyses. The analyses demonstrate empirically that Haldane’s model was flawed. As such, ReMine’s argument regarding human evolution form an ape-like ancestor being impossible due to Haldane’s dilemma is an illusion. ReMine’s position, of course, had other fatal flaws even before Haldane’s model was shown to be wrong, such as the use of mere assertion and personal incredulity in place of empirical evidence as justification for his claims on this matter.

    I will gladly continue this discussion when you provide documentation for your numbers and we can then continue on with what you perceive are other ‘major problems.’

    Scott L. Page, PhD.
     
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    DAVID PLAISTED
    Population geneticist Crowe had an article recently in which he
    asserted that at the rate of mutation assumed for the human-ape split,
    the human race should have died out by now.
    Thus there must be such a thing as error catastrophe and the problem
    is not just due to ReMine.

    However I do not think that Haldane's dilemma is valid and
    arguments to this effect can be found at my web page under the
    population genetics article -- but it is too technical for
    probably almost everyone here. The article may be found at
    www.cs.unc.edu/~plaisted/ce/
    under Population Genetics Made Simple
     
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    SCOTT PAGE

    Hi David,

    Which article (Crow) are you referring to? I am reading his essay in Nature (Jan. 1999) – is that the one you refer to? If so, he does not assert any such thing. Indeed, his statements lend credence to the papers I cited, especially the Science paper on sexual recombination. If you had another article in mind, please let me know.

    If, as you suggest, we should have died out by now as a species, it seems to me that there, in fact, is not such a thing as error catastrophe – or, more likely, there are ways to avoid it.

    I agree with your assessment of Haldane’s dilemma being a non-starter. I read your article and may write a critique of it – parts of it anyway – but I am pressed for time now and will only mention a few things.
    1. Many of your calculations seem forced and not reflective of reality (the parts about 200 million years and all that)
    2. You contradict another of your essays with regard to gene number.
    3. Your generation time of 30 years, yielding an ‘origin’ of humanity at 6000 years ago is unrealistic, and seems forced for the obvious reasons.
    4. Your conflation of the raw nucleotide differences between humans and chimps with the ‘Haldane limit’ – upon which many of your calculations were based – is seriously flawed. The amount of mutation is well within the estimates that can be seen in, for example, Li’s “Molecular Evolution” text. The biggest problem is the fact that the numbers you used – 70 million – includes unfixed mutations. This is true by necessity, since there is no way to remove SNPs from a phylogenetic analysis in which only one or a few specimens from each taxon is used, which is how such analyses are done.

    If you want to discuss this further, I will do so.

    Scott L. Page
     
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    DAVID PLAISTED
    Scott,
    I can't find the article from Crow for some reason. Can you post the
    abstract for the article "The Odds of Losing at Genetic Roulette" if you
    have it because we don't have convenient electronic access to Nature?
    I'm not sure anyway that it is the article I sought.

    If you want to critique my population genetics article you may but it's
    not a high priority with me. There are one or two things in it I may want
    to change sometime anyway.

    Dave Plaisted
     
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    SCOTT PAGE

    Hi David,

    The Crow article in Nature is just a News and Views essay, so there is not really an abstract. There are a couple of bolded sentences that introduce the piece - closest thing I can see to an abstract:

    The number of harmful mutations that arise in each generation has been measured, and it is surprisingly high. This supports one theory of why evolution favours sexual reproduction, but the consequences for human health are unclear.

    I hope that you make the appropriate corrections/clarifications soon.
     
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    DAVID PLAISTED

    Here are some web links about the Nature article by Adam Eyre-Walker and Peter Keightley computing the mutation rate corresponding to the assumed ape-human split:
    http://abcnews.go.com/sections/science/DailyNews/mutation990127.html

    http://nitro.biosci.arizona.edu/zbook/volume_1/chapters/vol1_12.html

    http://www.sciam.com/1999/0499issue/0499scicit4.html

    http://news.bbc.co.uk/low/english/sci/tech/newsid_264000/264191.stm


    The point is that if the mutation rate is as high as assumed for the ape-human split, humans should have died out unless something called "truncation selection" operates. Basically, this groups together harmful mutations to permit them to be eliminated more efficiently.

    My point here is not to argue against evolution in this way, since the number of genes is now thought to be less than it was when this article was published (this may reduce the problem). Right now I just want to argue that error catastrophe is a recognized concept and that if the mutation rate is high and truncation selection does not operate, a species will die out. I saw a reference once to an experiment on bacteria in which all combinations of three harmful mutations were introduced to see their combined effects (all 7 subsets). The results suggested that truncation selection does not operate. If this is so, then error catastrophe is real. I lost the reference, though.

    There is also a discussion of this issue in http://www.evolutionfairytale.com/

    see the article
    Monkey-Man Hypothesis Thwarted by Mutation Rates

    and the quotation near the end where the authors of the Genetics article say that truncation selection "seems unrealistic."

    Dave Plaisted
     
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    RUFUSATTICUS

    David referred to a paper by Eyre-Walker and Keightley. However, he did not
    give a full citation. This is surprising since he claims that it shows
    humans didn't come from apes. If it supported his argument why didn't he
    lead readers to the paper itself, instead of news articles and creationist
    interpretations? I got a copy of the paper and, after reading it,
    understand why he didn't link to it. In reality, the paper does nothing to
    support a creationist position. Here is the abstract.

    <BLOCKQUOTE>quote:</font><HR> It has been suggested that humans may suffer a high genomic
    deleterious mutation rate. Here we test this hypothesis by applying a
    variant of a molecular approach to estimate the deleterious mutation rate in
    hominids from the level of selective constraint in DNA sequences. Under
    conservative assumptions, we estimate that an average of 4.2
    amino-acid-altering mutations per diploid per generation have occurred in
    the human lineage since humans separated from chimpanzees. Of these
    mutations, we estimate that at least 38% have been eliminated by natural
    selection, indicating that there have been more than 1.6 new deleterious
    mutations per diploid genome per generation. Thus, the deleterious
    mutation rate specific to protein-coding sequences alone is close to the
    upper limit tolerable by a species such as humans that has a low
    reproductive rate
    , indicating that the effects of deleterious mutations
    may have combined synergistically. Furthermore, the level of selective
    constraint in hominid protein-coding sequences is atypically low. A large
    number of slightly deleterious mutations may therefore have become fixed in
    hominid lineages.<HR></BLOCKQUOTE>

    Eyre-Walker A and Keightly P D. High genomic deleterious mutation rates in
    hominids. Nature 397: 344-347 (1999)

    A key part of this paper is that mutation rates were estimated by comparing
    humans and chimps:
    <BLOCKQUOTE>quote:</font><HR>We estimated rates of synonymous substitution per nucleotide, and
    rates of substitution that result in changes in amino acids per codon, along
    the human lineage after the human-chimpanzee split for 46 protein-coding
    sequences from humans and chimpanzees, using another primate species as an
    outgroup.<HR></BLOCKQUOTE>

    Thus one cannot claim that the result of this paper is true without also
    accepting that the methods were true. Thus it is impossible to use the
    result of this paper without acknowledging that Humans and Chimps share a
    common ancestor. However, David argues that humans have too high of a
    mutation rate to have persisted if we shared an ancestor with chimps. If he
    is right, and Humans and Chimps didn't share a common ancestor, then it
    follows that the calculation of the mutation rate is wrong, rendering his
    entire argument useless.

    -RvFvS
     
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    DAVID PLAISTED

    Rufus seems to have missed my whole point -- I explicitly stated that
    in this posting I was not using the mutation rate argument as an
    argument against the chimp-human split. My reason for quoting the
    article Monkey-Man Hypothesis Thwarted by Mutation Rates was to
    highlight what it said about truncation selection. I encourage the
    readers to go to the link themselves and see what it says.
    Dave Plaisted
     
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    RUFUSATTICUS

    My bad, David. I thought you were supporting evolutionfairtale. My
    comments still apply to their argument though.

    <BLOCKQUOTE>quote:</font><HR> I encourage the readers to go to the link themselves and see what it
    says.<HR></BLOCKQUOTE>

    I further encourage reading to original papers, since the EFT is guilty of
    quote mining. Here is a link to the article in Genetics that EFT
    also refers to. http://www.genetics.org/cgi/content/full/156/1/297

    EFT:
    <BLOCKQUOTE>quote:</font><HR> Other vindication for this article comes from a paper in the science
    journal Genetics published 5 months after this article. They write

    "For U = 3, the average fitness is reduced to 0.05, or put differently,
    each female would need to produce 40 offspring for 2 to survive and
    maintain the population at constant size." (emphasis is EFT's)

    They also acknowledge that this number is probably an underestimate!

    "This assumes that all mortality is due to selection and so the actual
    number of offspring required to maintain a constant population size is
    probably higher."<HR></BLOCKQUOTE>

    Here is the entire paragraph.
    <BLOCKQUOTE>quote:</font><HR> The high deleterious mutation rate in humans presents a paradox. If
    mutations interact multiplicatively, the genetic load associated with such a
    high U would be intolerable in species with a low rate of reproduction
    (MULLER 1950 ; WALLACE 1981 ; CROW 1993 ; KONDRASHOV 1995 ; EYRE-WALKER and
    KEIGHTLEY 1999 ). The reduction in fitness (i.e., the genetic load) due to
    deleterious mutations with multiplicative effects is given by 1 - e-U
    (KIMURA and MORUYAMA 1966 ). For U = 3, the average fitness is reduced to
    0.05, or put differently, each female would need to produce 40 offspring for
    2 to survive and maintain the population at constant size. This assumes that
    all mortality is due to selection and so the actual number of offspring
    required to maintain a constant population size is probably higher. The
    problem can be mitigated somewhat by soft selection (WALLACE 1991 ) or by
    selection early in development (e.g., in utero). However, many mutations are
    unconditionally deleterious and it is improbable that the reproductive
    potential on average for human females can approach 40 zygotes. This
    problem can be overcome if most deleterious mutations exhibit synergistic
    epistasis
    ; that is, if each additional mutation leads to a larger
    decrease in relative fitness (KONDRASHOV 1995 ; CROW 1997 ; EYRE-WALKER and
    KEIGHTLEY 1999 ). In the extreme, this gives rise to truncation selection in
    which all individuals carrying more than a threshold number of mutations are
    eliminated from the population. While extreme truncation selection seems
    unrealistic, the results presented here indicate that some form of
    positive epistasis among deleterious mutations is likely
    . (emphasis
    mine)<HR></BLOCKQUOTE>

    Am I the only one who noticed that EFT quote-mined here? The authors
    clearly give reasons why the "40 offspring" calculation does not contradict
    human evolution. However, EFT seems oblivious to that fact.

    David, yes they disagree with extreme truncation but advocate positive
    epistasis among deleterious mutation. This occurs when the effects of
    deleterious are beyond additive. If mutation A reduces an individual's
    fitness by S1 and mutation B reduces fitness by S2, then positive epistasis
    occurs when an individual with both A and B has its fitness reduced by
    S1+S2+E12 where E12 is the reduction of fitness due to the interaction of
    mutation A and B. An interesting fact is that sexual reproduction actually
    increases the probability that A and B occur in the same individual and are
    removed from the population. In other words, sexual reproduction preserves
    beneficial mutations and removes deleterious ones. There is clearly nothing
    here that points to a recent human creation.

    -RvFvS
     
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    SCOTT PAGE

    <BLOCKQUOTE>quote:</font><HR>
    DAVID PLAISTED

    Here are some web links about the Nature article by Adam Eyre-Walker and Peter Keightley computing
    the mutation rate corresponding to the assumed ape-human split:
    <HR></BLOCKQUOTE>

    I have the paper in question. <BLOCKQUOTE>quote:</font><HR>


    The point is that if the mutation rate is as high as assumed for the ape-human split, humans should
    have died out unless something called "truncation selection" operates. Basically, this groups together
    harmful mutations to permit them to be eliminated more efficiently.<HR></BLOCKQUOTE>

    Truncation selection is only one possibility. The fact that we have not died out is testament to the probability that there are genetic mechanisms at play that we either don’t yet understand or didn’t think played a major role (e.g. sexual recombination).

    <BLOCKQUOTE>quote:</font><HR>

    My point here is not to argue against evolution in this way, since the number of genes is now thought to
    be less than it was when this article was published (this may reduce the problem). Right now I just want
    to argue that error catastrophe is a recognized concept and that if the mutation rate is high and
    truncation selection does not operate, a species will die out. I saw a reference once to an experiment on
    bacteria in which all combinations of three harmful mutations were introduced to see their combined
    effects (all 7 subsets). The results suggested that truncation selection does not operate. If this is so,
    then error catastrophe is real. I lost the reference, though.<HR></BLOCKQUOTE>

    There are differences between the way a prokaryotic genome operates and a eukaryotic genome operates. Error catastrophe is a recognized concept, I have never stated or implied differently. It is, however, at least as of a year or two ago, purely theoretical.

    <BLOCKQUOTE>quote:</font><HR>

    There is also a discussion of this issue in http://www.evolutionfairytale.com/

    see the article
    Monkey-Man Hypothesis Thwarted by Mutation Rates<HR></BLOCKQUOTE>


    I am saddened that you would read, and then actually link to that site. The author, an abrasive electrical engineer, has had his notions refuted time and again on several boards. Not to mention the fact that you are head and shoulders above that fellow intellectually. There have got to be more reliable sources for your information, David.
    <BLOCKQUOTE>quote:</font><HR>

    and the quotation near the end where the authors of the Genetics article say that truncation selection
    "seems unrealistic."

    Dave Plaisted
    <HR></BLOCKQUOTE>

    If that were so, as the question is asked, Why are we still here? Something is going on…
     
  13. Administrator2

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    RADIOCHEMIST

    It has been suggested by Helen and others that the human race is
    increasingly burdened by bad mutations that have led to all sorts
    of health problems.
    However, there is very little empirical evidence that the genetic
    burden is increasing. In all measurable ways, the human species is
    increasingly successful, an outcome that would not be expected if
    the genetic burden is increasing. For example, the human population
    is at an all time high. The population is several times what it
    was a few hundred years ago. In addition, the average expected
    life span is much longer than a few hundred years ago. So if there
    is a bad effect of all these alleged mutations, it is very difficult
    to find. I agree that there are some bad mutations in humans, but
    I think it is far from proven that these have increased in recent
    times. Certainly they have not increased enough to produce
    a measurable effect in terms of a declining population. That really
    is the only realistic way to measure the success of a species.

    The unusual success of the human species can be explained in terms
    of ancient mutations that led to speech and the ability to transfer
    knowledge between generations. Man is far more successful at that
    than other animals. Therefore it seems that these ancient mutations
    are turning out to be far more important than any recent mutations
    that may have produced physical problems. Our well being is still
    being influenced by these old beneficial mutations and this effect
    is likely to continue for several thousand years into the future,
    with effects that far outweigh the effects of other mutations.

    The intelligence of other animals is often underestimated, it
    seems to me. Last night I was playing with our Border Collie and
    she understands several words even though her age is only 7
    months. She clearly understands the names of humans in our
    family, as well as the names of her toys. When told to go
    get a "squeeky toy" she will go get that toy and ignore
    other toys that she likes better. When told to take a ball
    to a certain person, she will do it. She has really very
    substantial intelligence, but is lacking in the ability
    to talk. I think that only speech separates some animals from
    humans.


    RADIOCHEMIST
     
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    HELEN

    A few points. Scott page wrote:
    <BLOCKQUOTE>quote:</font><HR> Error catastrophe is a recognized concept, I have never stated
    or implied differently. It is, however, at least as of a year or two
    ago, purely theoretical.<HR></BLOCKQUOTE>

    I believe it is primarily a mathematical concept as applied to
    population genetics. That would, I think, take it outside the realm of
    philosophically theoretical and put it, at least, in mathematically
    theoretical, which gives it a bit more status.

    In the post before that one, RufusAtticus had said, “ In other words,
    sexual reproduction preserves beneficial mutations and removes
    deleterious ones.


    And all I could think of was that then sexual reproduction among humans
    was certainly not doing its job:

    From National Geographic in October of 1999, a list of known results of
    negative mutations in the human genome.

    <BLOCKQUOTE>quote:</font><HR>Chromosome 1
    -- malignant melanoma
    -- prostate cancer
    -- deafness

    Chromosome 2
    -- congenital hypothyroidism
    -- colorectal cancer

    Chromosome 3
    -- susceptibility to HIV infection
    -- small-cell lung cancer
    -- dementia

    Chromosome 4
    -- Huntington's Disease
    -- polycystic kidney disease

    Chromosome 5
    -- spinal muscular atrophy
    -- endometrial carcinoma

    Chromosome 6
    -- hemochronatosis
    -- dyslexia
    -- schizophrenia
    -- myoclonus epilepsy
    -- estrogen resistance

    Chromosome 7
    -- Growth hormone deficient dwarfism
    -- pregnancy-induced hypertension
    -- cystic fibrosis
    -- severe obesity

    Chromosome 8
    -- hemolytic anemia
    -- Burkitt's lymphoma

    Chromosome 9
    -- dilated cardiomyopathy
    -- fructose intolerance

    Chromosome 10
    -- congenital cataracts
    -- late onset cockayne syndrome

    Chromosome 11
    -- sickle cell anemia
    -- albinism

    Chromosome 12
    -- inflammatory bowel disease
    -- rickets

    Chromosome 13
    -- breast cancer, early onset
    -- retinoblastoma
    -- pancreatic cancer

    Chromosome 14
    -- leukemia/ T-cell lymphoma
    -- goiter

    Chromosome 15
    -- Marfan's syndrome
    -- juvenile epilepsy

    Chromosome 16
    -- polycystic kidney disease
    -- familial gastric cancer
    -- Tuberous sclerosis-2

    Chromosome 17 (done in detail as an example)

    [blockquote]RP13 -- retinitis pigmentosa
    CTAA2 -- cataract
    SLC2A4 -- diabetes susceptibility
    TP53 -- cancer
    MYO15 -- deafness
    PMP22 -- Charcot-Marie-Tooth neuropathy
    COL1A1 -- osteogenesis imperfecta;
    osteoporosis
    SLC6A4 -- anxiety-related personality traits
    BLMH -- Alzheimer's disease susceptibility
    NF1 -- neurofibromatosis
    RARA -- leukemia
    MAPT -- dementia
    SGCA -- muscular dystrophy
    BRCA1 -- breast cancer; ovarian cancer
    PRKCA -- pituitary tumor
    MPO -- yeast infection susceptibility
    GH1 -- growth hormone deficiency
    DCP1 -- myocardian infarction susceptibility
    SSTR2 -- small-cell lung cancer [/blockquote]

    Chromosome 18
    -- diabetes mellitus
    -- familial carpal tunnel syndrome

    Chromosome 19
    -- myotonic dystrophy
    -- malignant hyperthermia

    Chromosome 20
    -- isolated growth hormone deficiency
    -- fatal familial insomnia
    -- Creutzfeldt-Jakob's disease

    Chromosome 21
    -- autoimmune polyglandular disease
    -- amyotrophic lateral sclerosis

    Chromosome 22
    -- Ewing's sarcome
    -- giant-cell fibroblastoma

    X Chromosome
    -- colorblindness
    -- mental retardation
    -- gout
    -- hemophilia
    -- male pseudohermaphroditism

    Y Chromosome
    -- gonadal dysgenesis

    Mitochondrial DNA
    -- Leber's hereditary optic neuropathy
    -- diabetes and deafness
    -- myopathy and cardiomyopathy
    -- dystonia

    <HR></BLOCKQUOTE>
     
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    RUFUSATTICUS

    <BLOCKQUOTE>quote:</font><HR> In the post before that one, RufusAtticus had said, " In other
    words,
    sexual reproduction preserves beneficial mutations and removes
    deleterious ones."

    And all I could think of was that then sexual reproduction among humans
    was certainly not doing its job.<HR></BLOCKQUOTE>

    And all I could think of was that you missed the entire point. Read the
    scientific papers above. They clearly conclude that sexual reproduction
    certainly is doing its job; otherwise, humans would be extinct. I
    have no clue how your list is support your point, since no one is claiming
    that negative mutations don't exist or are completely eliminated by sexual
    reproduction. You do realize that I used the word "remove," as in "I
    removed a book from the shelf." Your reply then is similar to "you couldn't
    have removed a book since there are still books on the shelf." Maybe you'd
    be correct if I said "completely eliminates;" however, I didn't. Do you
    understand how your criticism is not valid?

    -RvFvS
     
  16. Administrator2

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    SCOTT PAGE

    <BLOCKQUOTE>quote:</font><HR>A few points. Scott page wrote:

    Error catastrophe is a recognized concept, I have never stated or implied differently. It is, however, at least as of a year or two ago, purely theoretical.

    I believe it is primarily a mathematical concept as applied to population genetics. That would, I think, take it outside the realm of philosophically theoretical and put it, at least, in mathematically theoretical, which gives it a bit more status.<HR></BLOCKQUOTE>

    I was not aware that mathematical theoretical constructs have more status than actual observations. Mathematical models seem to be preferred by some over empirical evidence, and the reasons for this are obvious.

    <BLOCKQUOTE>quote:</font><HR>
    In the post before that one, RufusAtticus had said, “ In other words, sexual reproduction preserves beneficial mutations and removes deleterious ones.

    And all I could think of was that then sexual reproduction among humans was certainly not doing its job:

    From National Geographic in October of 1999, a list of known results of negative mutations in the human genome. <HR></BLOCKQUOTE>

    We have only been able to IDENTIFY genes associated with various disorders for a few decades, tops. Certainly, the specific genetic loci involved have only within the past few years been pinpointed. It is a technology issue.

    It should not surprise anyone without an agenda that the number of diseases associated with a definite genetic component is growing and will probably continue to grow – we can actually discover them now. Prior to the knowledge that many diseases have a genetic component, the causes were attributed to something else.

    In order for your implication to have any scientific merit at all, you would need to supply a list of new disorders that have a genetic component.
    Look at your list – how many of the disorders are ‘new’?
    This one?
    malignant melanoma


    Or maybe it is this one?

    congenital hypothyroidism


    My bet is that THIS one is a brand new disorder:

    dementia


    As for your comment about sexual recombination ‘not doing its job’, nobody said that ALL deleterious mutations are removed, and to imply otherwise is a misrepresentation.
    Evidence – ACTUAL evidence – indicates that sex keeps the accumulation of them at a lower rate than would otherwise occur.
    I thought that was fairly obvious from the portions of the paper I posted.
     
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    RADIOCHEMIST

    Helen: "From National Geographic in October of 1999, a list of known
    results of negative mutations in the human genome."

    (Helen then gives a long list)


    Helen, Can you explain why, with all these harmful mutations, that
    the human population is at the highest number ever, and still
    growing at a rapid rate?

    RADIOCHEMIST
     
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    THE BARBARIAN

    A more pertainent question might be:
    "Why, if this theoretical number-crunching is correct, do we see records for
    human performance continue to be broken? Why has it been necessary to
    repeatedly raise the score needed to obtain a 100 on an IQ test? This
    Barbarian sees a conflict between theory and reality here.

    If we are degenerating, it's certainly puzzling as to why the evidence
    indicates exactly the opposite.

    [ March 01, 2002, 11:56 AM: Message edited by: Administrator ]
     
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    HELEN

    For Scott, Pat, and Radiochemist…

    Scott: you wrote, I was not aware that mathematical theoretical constructs have more status than actual observations.

    That was not what I said. I said error catastrophe is a mathematical theoretical concept and as such is probably better that a PHILOSOPHICALLY theoretical concept. I was dealing with theory in both cases, not with actual observations.

    However, I do very much agree with you concerning your next statement:
    Mathematical models seem to be preferred by some over empirical evidence, and the reasons for this are obvious.

    This is exactly what most computer models and the game theory models do! I prefer empirical evidence, too.

    Then, regarding the NG list of problems associated with mutations, you wrote,
    We have only been able to IDENTIFY genes associated with various disorders for a few decades, tops. Certainly, the specific genetic loci involved have only within the past few years been pinpointed. It is a technology issue.

    Oh, I think there will be a few surprises involved for people. Here is one about something much simpler than human beings. Here is a mutations which looked like it had a short term benefit, but was deleterious in the long run. That is something which may not have just happened once in the history of the world, do you think?
    The abstract is at: http://www.pnas.org/cgi/content/abstract/032671599v1
    <BLOCKQUOTE>quote:</font><HR>Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for
    microsatellite stability and maintenance of genome integrity
    Natasha P. Degtyareva*, Patricia Greenwell*, E. Randal Hofmann,, Michael
    O. Hengartner,, Lijia Zhang§,, Joseph G. Culotti§,, and Thomas D. Petes*,
    Contributed by Thomas D. Petes, December 14, 2001

    Mismatch repair genes are important in maintaining the fidelity of DNA
    replication. To determine the function of the Caenorhabditis elegans
    homologue of the MSH2 mismatch repair gene (msh-2), we isolated a strain
    of C. elegans with an insertion of the transposable element Tc1 within
    msh-2. Early-passage msh-2 mutants were similar to wild-type worms with regard
    to lifespan and meiotic chromosome segregation but had slightly reduced
    fertility. The mutant worms had reduced DNA damage-induced germ-line
    apoptosis after genotoxic stress. The msh-2 mutants also had elevated
    levels of microsatellite instability and increased rates of reversion of the
    dominant unc-58(e665) mutation. In addition, serially passaged cultures
    of msh-2 worms died out much more quickly than those of wild-type worms.
    These results demonstrate that msh-2 function in C. elegans is important in
    regulating both short- and long-term genomic stability.

    * Department of Biology and Curriculum in Genetics and Molecular
    Biology, University of North Carolina, Chapel Hill, NC 27599-3280; Cold Spring
    Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; Institute of
    Molecular Biology, University of Zurich, Room 55 L 22, Winterthurer
    Strasse 190, CH-8057 Zurich, Switzerland; § Department of Molecular and Medical
    Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8; and Samuel
    Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON, Canada
    M5G 1X5 <HR></BLOCKQUOTE>
    You then wrote: It should not surprise anyone without an agenda that the number of diseases associated with a definite genetic component is growing and will probably continue to grow – we can actually discover them now. Prior to the knowledge that many diseases have a genetic component, the causes were attributed to something else.

    Presumably we will then be able to accumulate a list of preserved known good mutations, too, right?


    In order for your implication to have any scientific merit at all, you would need to supply a list of new disorders that have a genetic component.

    Why? My point was that sexual reproduction is not doing a very good job getting rid of these. Therefore the longer they have been around, the worse a job sexual reproduction is doing eliminating them! New mutations are presumably getting wiped out all the time. But look at these – and you are right, they are not new! And they are of no benefit to any human being alive. So why have they not been eliminated, as evolution says they should?

    And you stated in closing, “evidence…indicates that sex keeps the accumulation of them at a lower rate than would otherwise occur” to which I definitely agree. That was never my argument at all! Just take a look at that number from NG and be grateful!

    But again, where are the positive mutations?



    To Radiochemist and Pat Parson: you are both assuming an ancient age for humanity. Pat is also assuming a lower level of intelligence in the past. I disagree with both assumptions. We are a young creation, and first of all, our growth has nothing to do with evolution – it has to do with the sort of advanced technology which is allowing more people to live. The world’s birth RATE, as a whole, is probably somewhat less than in times past. But we have more children living now and adults living longer.

    Secondly, to Pat, human performance in both athletics and intelligence is higher than it was in the past few generations. We have no way of comparing with people of several thousand years ago. We have also improved both training methods in athletics and how to teach for the test in academics. I’m not sure either indicates any actual improvement in the human race, simply a greater degree of specialization.
     
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    THE BARBARIAN

    Helen Asks:
    But again, where are the positive mutations?


    There's the mutation that removed the binding site on cells where HIV
    attached. This mutation provides an absolute immunity to AIDS.
    Population geneticists have tracked it back to Central Asia. There's
    another that permits HIV infection, but the individual is asymptomatic.
    This has been located in Africa, where a number of women have been found to
    have high HIV titers, but no symptoms.

    There's that clan in Italy, where investigators tracked back a mutation in a
    single individual, which provides resistance to hardening of the arteries.

    There are a number of hemoglobin mutations that provide resistance to
    malaria. All of these certainly are favorable to the populations having
    them, given the environment in which they evolved.

    Helen:
    To Radiochemist and Pat Parson: you are both assuming an ancient age for
    humanity.


    No, we accept the evidence for an ancient age for humanity. No assumptions
    necessary. When we find humans hundreds of thousands of years ago, it's
    not hard to realize that humans have been around for a long time.


    Helen:
    Pat is also assuming a lower level of intelligence in the past.


    Fact is, intelligence was lower than it is today, just twenty years ago.
    That's why they had to up the score needed to keep the average IQ at 100.
    Granted, educational reforms may have something to do with it. But still,
    if humans were degenerating, you would surely see evidence going the other
    way.

    Helen:
    I disagree with both assumptions. We are a young creation,


    Young creation is your assumption. And as you've seen, it is contradicted
    by the evidence. Not just varves, (confusion with other sorts of laminae
    notwithstanding), it's many things. Coral atolls show that the Earth is
    much older than any YE theory has it. So does all sorts of other evidence,
    including historical records from civilizations that never noticed the
    supposed worldwide flood.

    Helen:
    Secondly, to Pat, human performance in both athletics and intelligence is
    higher than it was in the past few generations. We have no way of comparing
    with people of several thousand years ago.


    We merely know we are smarter than humans a few decades ago. Still, if we
    were degenerating, that would not be the case. Why are our kids a little
    smarter each generation? It sure isn't because there's some kind of
    genetic meltdown.


    Helen:
    We have also improved both training methods in athletics and how to teach
    for the test in academics.


    IQ has nothing to do with "teach the test". It's just a measure of mental
    ability. And we're getting smarter. Granted, improved training has made
    many athletes better. But if we were degenerating, that wouldn't be
    possible, either. If the only evidence shows we are getting better, there
    isn't much point in claiming that we are degenerating.

    Helen:
    I’m not sure either indicates any actual improvement in the human race,
    simply a greater degree of specialization.


    I don't see much hope in claiming that the general increase in intelligence
    of the population is evidence for "specialization". And the athletes for
    whom human performance has risen so rapidly still come from the general
    population. Granted, good atheletes tend to come from athletic familes.
    But that would seem to contradict your point as well.

    [ March 01, 2002, 11:57 AM: Message edited by: Administrator ]
     

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