The Genetic Degeneration of Humans

[Sean Pitman]

The Genetic Degeneration of Humans

Sean Pitman M.D.
www.naturalselection.0catch.com
http://naturalselection.0catch.com/Files/dnamutationrates.html


As with mitochondrial DNA mutation rates, the mutation rates of
nuclear DNA have often been calculated based on evolutionary scenarios
rather than on direct methods. By such methods, the average mutation
rate for eukaryotes in general is estimated to be about 2.2 x 10e-9
mutations per base pair per year.29 With a 20 year average generation
time for humans, this works out to be around 4.4 x 10e-8 mutations per
base pair per generation. Since most estimates of the size of the
diploid human genome run around 6.3 billion base pairs, this mutation
rate would give the average child around 277 mutational differences
his or her parents. This sounds like quite a high number and it is in
fact on the high end of the spectrum when compared to studies looking
more specifically at human mutation rates verses eukaryotic mutation
rates in general. A particular study by Nachman and Crowell estimated
the average mutation rate specifically in humans by comparing control
sequences in humans and chimpanzees. Using these sequence
comparisons, "The average mutation rate was estimated to be ~2.5 x
10e-8 mutations per nucleotide site or 175 mutations per diploid
genome per generation" [Based on a higher diploid genome estimate of 7
billion base pairs].30 For comparison, consider that the mutation rate
for prokaryotes, (like bacteria) is somewhere around 1 x 10e-9 per
base pair per generation (By direct methods).14,15

These estimates do actually seem reasonable since they seem to match
the error rates of DNA replication and repair that occur between the
formation of a zygote in one generation and the formation of a zygote
in the next generation. In the illustration (31) below, notice that
from fertilization to the formation of a woman's first functional
gamete, it takes about 23 mitotic divisions. Men, on the other hand,
contribute about twice as many germ line mutations as women do.33 At
least part of the reason is that their stem cells keep dividing so
that the older a man gets before having children more mitotic
divisions occur.

Now, consider that each diploid fertilized zygote contains around 6
billion base pairs of DNA (~3 billion from each gamete/parent, using a
conservative round number).32 From cell division to cell division, the
error rate for DNA polymerase combined with other repair enzymes is
about 1 mistake in 1 billion base pairs copied.42 At this rate, there
are about 6 mistakes with each diploid cell replication event. With a
male/female average of 29 mitotic divisions before the production of
the next generation, this works out to be about 175 mutations per
generation. Of course, this is right in line with the mutation rates
that are based on evolutionary scenarios. However, some estimates
place the overall mutation rate as low as 1 mistake in 10 billion base
pairs copied.43 At this rate, one would expect around 0.6 mistakes
with each replication event and only around 17 mutations per person
per generation. In any case, since the rate of 175 mutations per
generation is more in line with most of the current estimates for
humans, this rate will be used as the basis for the rest of this
discussion.

Such a high mutation rate (be it 17.5 or 175 per generation) might be
a larger problem than it is for humans if it were not for the fact
that much of the human genome does not seem to code for anything. The
amount of this non-coding DNA has been estimated by calculating the
coding portion of DNA and subtracting this from the total genomic real
estate. It seems as though the average coding portion of a human gene
is around 1,350 base pairs in size. Of course, this gene would code
for a protein averaging 450 amino acids.38 There is some argument as
to the total number of genes in the human genome however. For many
years it was thought that humans had between 70,000 to 140,000 genes.
However, scientists working on the human genome project made a
surprising discovery. When they finished the project in February of
2001, they estimated that the actual gene count was somewhere between
30,000 to 40,000 genes.39 But a year later, in February of 2002, at
the annual meeting of the American Association for the Advancement of
Science (publisher of Science), one of the presenters, Victor
Velculescu, suggested that the real number of genes in the human
genome may actually be closer to 70,000 genes after all. He and his
colleagues, at Johns Hopkins University in Baltimore, Maryland, have
gone back to the lab to look for genes that the computer programs may
have missed. Their technique, called serial analysis of gene
expression (SAGE), works by tracking RNA molecules back to their DNA
sources. After isolating RNA from various human tissues, the
researchers copy it into DNA, from which they cut out a kind of
genetic bar code of 10 to 20 base pairs. Velculescu proposes that the
vast majority of these tags are unique to a single gene. If so, the
tags can then be compared to the human genome to find out if they
match up with genes discovered by the computer algorithms. Velculescu
stated that only about half of the tags he used match the genes
identified earlier in the genome project. Therefore, he suggests that
the human inventory of genes had been underestimated by about half.
The reason for the disparity may be that the standard computer
programs were largely developed for the genomes of simple
(prokaryotic) organisms, not for the more complex sequences found in
the genomes of humans and other eukaryotes. "We're still not very good
at predicting genes in eukaryotes," said Claire Fraser of The
Institute for Genomic Research in Rockville, Maryland. "It is entirely
possible that there could be more than 32,000 genes, and SAGE is an
important approach to finding them… You absolutely have to go back
into the lab and get away from the computer terminal."40

So, it seems as though there is still some question as to exactly how
many genes the human genome contains. But, for the sake of argument,
lets go with a lower estimate of ~40,000 genes. With each gene
averaging 1,350 base pairs in size, only around 108 million base pairs
out of 6 billion base pairs (diploid) would code for anything. This
is only around 1.8% of the total genome.

Much of the rest of the human genome (At least 50%) is composed of a
large amount of "repetitive DNA" that is made up of similar sequences
occurring over and over.33,38 At least some of the other 48% of the
genome is thought to provide structural integrity as well as
regulating the production of the coding sequences of DNA as far as
when, where, and how much protein to make. However, exactly how much
of the non-protein-coding genome is functional is not clearly
understood.

In any case, since mutations are the only possible source of novel
genomic function in naturalistic evolution, we should consider a few
facts about these mutations. Since mutations are thought to be purely
random events causes by errors of replication and maintenance over
time, they occur over the entire genome in a fairly random fashion
with each generation. With this in mind, lets say that a given
lineage has experienced 10,000 mutations over the course of time (~66
generations in humans). Of these 10,000 mutations, at least 5,000 of
them would affect the "junk" DNA. Of the remaining 5,000 mutations,
only around 200 (2%) of them would affect the protein coding portions
of the genome. Of these most calculations assume that 10% to 70% are
functionally neutral. This estimate is based on a detrimental
mutation rate of 1 to 3 per person per generation with at least some
scientists (Nachmann and Crowell, 2000) favoring at least 3 or more.30
Nachmann and Crowell, from the Department of Evolutionary Biology at
the University of Arizona, suggest that the average per generation
accumulation of between 1 and 3 detrimental mutations "is likely to be
biased downward because we have considered only nonsynonymous sites as
potential targets for deleterious mutations."30 Of course, this means
that between 30% to 90% (most likely 90%) of mutations affecting
coding sequences are detrimental.

Given 10% as the most likely neutral mutation rate estimate for
mutations involving protein coding genetic sequences, of the 200
mutations affecting coding regions of DNA, about 180 of them would
result in a functional change that could be affected by natural
selection (1.8% of the total number of mutations). Since detrimental
mutations outnumber beneficial mutations by about 1,000 to 1 (34,36)
odds are that most if not all 180 mutations would result in a
selectively detrimental change in function (Only 0.0018% of total
mutations would be beneficial).

With the rates detailed so far, it would take around 9,700,000
mutational events to produce just one beneficial mutation in the
entire protein-coding region of the human genome (~40,000 gene pairs =
80,000 genes in a diploid cell). This works out to be around 55,500
generations to evolve just one beneficial mutation among 80,000 genes.
Of course, from the perspective of a single gene, this works out to
be around 4.4 billion generations on average, to get just one
beneficial mutation. Of course, with a population of one billion,
there would be two billion copies of this gene. Odds are that at
least one of these copies will get a beneficial mutation in just two
or three generations. Of course, then this beneficial mutation will
increase in the population in proportion to the average reproductive
rate of the population as well as the reproductive benefit that this
mutation provides. So, where is the problem?

The problem is that beneficial mutations come at a high cost. The
reason for this is that every beneficial mutation comes with 1,000 or
so detrimental mutations. In order for evolution to proceed in a
positive direction (away from extinction) there must be some way to
create a favorable balance of beneficial mutations over detrimental
mutations in a given population. The reason for this is that
evolution is dependent on mutations as a source of new information.
If there were no mutations, there would be no evolution. Also, if all
mutations were negative in a given population (ie: resulting in loss
of beneficial function), that population would eventually experience
extinction. Therefore, for a population to live and evolve
indefinitely, there have to be a few beneficial mutations every now
and then . . . but how many and how often? What rate and ratio of
detrimental vs. beneficial mutations is needed to keep a population
from extinction and yet allow it to evolve and maintain new beneficial
functions over time?

If the average beneficial mutations and detrimental mutations are
equivalent in their absolute effects on the organism (each one having
its equivalent on the other side), this would mean that an organism
with one beneficial and one detrimental mutation would have a neutral
advantage as far as survival and reproductive fitness. One beneficial
mutation and two detrimental mutations would have a negative selective
value for that organism and its offspring. Likewise, two beneficial
mutations and one detrimental mutation would have a positive selective
value . . . and so on.

In considering this question further, let's use our above rate of 175
new mutations per individual (6 billion base pairs) per generation.
Of these, about 171.997 of them would be selectively neutral and
approximately 3 would be selectively detrimental, on average. Only
0.003 of them would be beneficial. Odds are that an average offspring
in any given generation will have a selective disadvantage that is
weighted 1000 to 1 in favor of detrimental over beneficial mutational
events. What would have to happen to successfully absorb this kind of
bad Karma?

What we really need to do is give the population as a whole a larger
weight of beneficial over negative mutations. How can this be done?
What would happen if we had a steady state population of one billion
individuals? Would this stabilize the population's decline toward
extinction?

With a steady state population of one billion, we would expect around
175 billion mutations in our population per generation. Of these,
around 171.997 billion of them would be neutral, 3 billion of them
would be detriment, and around 3 million of them would be beneficial
(1000 to 1 ratio). In this population of one billion, how many of the
offspring, in a given generation, will have a positive mutational
balance (ie: more beneficial than detrimental mutations)?

With these numbers, one beneficial mutation will occur every 58,479
mutations. So, with an average of 175 mutations per individual, an
average of 1 out of 334 individuals will have one beneficial mutation.
Of course, on average, this person would have 2 other detrimental
mutations (~3 non-neutral mutations per person per generation).
Obviously, this is an overall detrimental balance. We need to have
more beneficial mutations than detrimental ones. So, what are the
odds that we will have more beneficial mutations than detrimental
mutations in a given individual in a given generation?

If the likelihood of one beneficial mutation occurring in a given
individual is 1 in 334 individuals, what are the odds that no
detrimental mutations will occur in an individual with a beneficial
mutation? With 2% of all mutations being detrimental, the odds that
no detrimental mutations will occur in 174 mutational events (making
175 mutations total) are the same odds that all 174 mutations will be
either neutral or beneficial. The likelihood of this happening is 1
in 20 individuals. So, the odds of getting a beneficial mutation
without any detrimental mutations would be 1 in 6,680 individuals. In
our population of 1 billion, we would find only 150,000 or so
individuals with a beneficial mutational balance in one generation, on
average. The problem is that this is only 0.015% of the total
population. Around 48 million would have a neutral balance (~4.8%),
and the rest of the population, all 951.8 million (~95.1%) of them
would have a detrimental mutational balance after just one generation.
In other words, more than 95% of the population would experience a
loss of overall genetic function in just one generation.

This does not look very promising for the survival of our population
much less improved survival. It appears as though the human species
is devolving, not evolving. There is a steady loss of genetic
function that is leaving the gene pool far faster than it can be
replaced by even the potential gains of beneficial mutations. The
problem is that even if everyone with a detrimental mutational balance
died without producing offspring, those with a neutral or positive
mutational balance would have to produce over 20 offspring per person
(over 40 per female) in order to maintain the population's size and
avoid extinction. Since this is unlikely, some other process must be
getting rid of the detrimental mutations faster than they are put into
the population. Clearly, output of the harmful mutants must be
greater than their input in order for a population to avoid
extinction.

Some scientists propose that detrimental mutations are somehow
concentrated in a small portion of the population via genetic
recombination.37 Then, when these unfortunate individuals die off
prematurely, the detrimental mutations leave the population with them.
How this could be accomplished through naturalistic means is not
entirely clear. This is the theory, but no one seems able to explain
how this could even theoretically work in real life.

Nachmann and Crowell detail the perplexing situation at hand in the
following conclusion from their fairly recent paper on human mutation
rates:


"The high deleterious mutation rate in humans presents a paradox. If
mutations interact multiplicatively, the genetic load associated with
such a high U [detrimental mutation rate] would be intolerable in
species with a low rate of reproduction [like humans and apes etc.] .
. .
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 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; this is, if each additional
mutation leads to a larger decrease in relative fitness. 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 death of all those with a detrimental
mutational balance], the results presented here indicate that some
form of positive epistasis among deleterious mutations is likely."30


Nachmann and Crowell find the situation a very puzzling one. How does
one get rid of all the bad mutations faster than they are produced?
Does their hypothesis of "positive epistasis" adequately explain how
detrimental mutations can be cleared faster than they are added to a
population? If the functional effects of mutations were increased in
a multiplicative instead of additive fashion, would fewer individuals
die than before? As noted above, even if every detrimental mutation
caused the death of its owner, the reproductive burden of the
survivors would not diminish, but would remain the same. For example,
lets say that all those with at least three detrimental mutations die
before reproducing. The population average would soon hover just
above 3 deleterious mutation rates. Over 95% of each subsequent
generation would have 3 or more deleterious mutations as compared with
the original "neutral" population. The death rate would increase
dramatically. In order to keep up, the reproductive rates of those
surviving individuals would have to increase in proportion to the
increased death rate. The same thing would eventually happen if the
death line were drawn at 100, 500, 1000, 10000 or more deleterious
mutations. The only difference would be the length of time it would
take a given population to build up a lethal number of deleterious
mutations from a relatively "neutral" starting point. The population
might survive fairly well for many generations without having to
resort to huge increases in the reproduction rate. However, without
getting rid of the accumulating deleterious mutations, the population
would eventually find itself experiencing an exponential rise in its
death rate as its average population crossed the line of lethal
mutations.

Since the theory of positive epistasis does not seem to help the
situation much, some other process must be found to explain how to
preferentially get rid of detrimental mutations from a population.
Consider an excerpt from a fairly recent Scientific American article
entitled, "The Degeneration of Man" :


"According to standard population genetics theory, the figure of three
harmful mutations per person per generation implies that three people
would have to die prematurely in each generation (or fail to
reproduce) for each person who reproduced in order to eliminate the
now absent deleterious mutations [75% death rate]. Humans do not
reproduce fast enough to support such a huge death toll. As James F.
Crow of the University of Wisconsin asked rhetorically, in a
commentary in ‘Nature' on Eyre-Walker and Keightley's analysis: "Why
aren't we extinct?"
Crow's answer is that sex, which shuffles genes around, allows
detrimental mutations to be eliminated in bunches. The new findings
thus support the idea that sex evolved because individuals who (thanks
to sex) inherited several bad mutations rid the gene pool of all of
them at once, by failing to survive or reproduce.
Yet natural selection has weakened in human populations with the
advent of modern medicine, Crow notes. So he theorizes that harmful
mutations may now be starting to accumulate at an even higher rate,
with possibly worrisome consequences for health. Keightley is
skeptical: he thinks that many mildly deleterious mutations have
already become widespread in human populations through random events
in evolution and that various adaptations, notably intelligence, have
more than compensated. "I doubt that we'll have to pay a penalty as
Crow seems to think," he remarks. 'We've managed perfectly well up
until now.'"37


Even though I do not agree with much of Crow's thinking, I do agree
with him when he says that harmful mutations are accumulating in the
human gene pool far faster than they are leaving it. However, on what
basis does he suggest that harmful mutations spontaneously cluster
themselves into "bunches" for batch elimination from the gene pool of
a given population? Crow does not suggest a mechanism nor does it
seem remotely intuitive as to how this even might occur via
naturalistic means.

Also, Keightley is far too optimistic in my view. He assumes that
because evolution has happened in the past, that somehow evolution
will solve the problem. He fails to even consider the notion that
perhaps humans, apes, and other species with comparably long breeding
times have been gradually degenerating all along. Perhaps evolution
only proceeds downhill (devolution)? Perhaps mutations do not improve
functions over time so much as they remove functions over time in
species with slow generation times?

Then again, even if the degenerative effects of mutations were somehow
solved in populations with slow reproduction times, the addition of
new information to the gene pool often involves the crossing of huge
oceans of neutral/nonfunctional sequence gaps that would take, for all
practical purposes, forever to cross.41 It seems as though mutations,
averaged over an extended period of time, tend toward loss and
extinction rather than toward any sort of improvement or gain.

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[Ron Okimoto]

Sean Pitman wrote:

> The Genetic Degeneration of Humans
>
> Sean Pitman M.D.
> www.naturalselection.0catch.com
> http://naturalselection.0catch.com/Files/dnamutationrates.html

I'd like to read the original creationist source for this post. I want to compare your version to the original to see if it is you that is
messing up the arguments or the original perpetrator. Where did you get the citations and the original argument?

>

Snip:

I'll accept the 175 mutations per generation argument. This isn't a really high rate. As you know for bacterial work we can get the
mutation rate up to 1 in 10^4-10^5 by just starving the bacteria and enough of them survive and even adapt to the starvation conditions.

> important approach to finding themÖ You absolutely have to go back

> into the lab and get away from the computer terminal."40

They are going to have the chicken genome sequence to compare to the mammlian sequence and it will be better than the fish sequence in
determining the number of genes in the genome. Can you guess why? We expect this due to the nature of common descent, you have to claim
that the designer did it that way for some unknown reason when he didn't have to. What was one of the reasons cited for sequencing the
chicken genome? Why can we predict these things based on evolutionary relationships, and you have to guess at what your designer might have
done?

>
>
> So, it seems as though there is still some question as to exactly how
> many genes the human genome contains. But, for the sake of argument,
> lets go with a lower estimate of ~40,000 genes. With each gene
> averaging 1,350 base pairs in size, only around 108 million base pairs
> out of 6 billion base pairs (diploid) would code for anything. This
> is only around 1.8% of the total genome.
>
> Much of the rest of the human genome (At least 50%) is composed of a
> large amount of "repetitive DNA" that is made up of similar sequences
> occurring over and over.33,38 At least some of the other 48% of the
> genome is thought to provide structural integrity as well as
> regulating the production of the coding sequences of DNA as far as
> when, where, and how much protein to make. However, exactly how much
> of the non-protein-coding genome is functional is not clearly
> understood.

probably an over estimate.

>
>
> In any case, since mutations are the only possible source of novel
> genomic function in naturalistic evolution,

No, recombination is a very important tool. You should understand this because you are claiming that you can use recombination to create
all the various alleles that we see in a given species. It works both ways, but we have millions of years and you only have a few
thousand. Some genes are over a million base-pairs in length and would have a recombination event in them about in about 1% of every
meiotic event. Most are much shorter than that (only a few thousand, but the recombination rate is probably as high as the mutation rate
within a gene.

> we should consider a few
> facts about these mutations. Since mutations are thought to be purely
> random events causes by errors of replication and maintenance over
> time, they occur over the entire genome in a fairly random fashion
> with each generation.

They aren't random except in the fact that we can't predict which ones will happen. We know that transitions (purine to purine or
pyrimidine to pyrimidine) mutations are much more likely at any given position than are transversions (purine to pyrimidine). We also know
that CG sequences are much more likely to mutate than other sequences. We also know that there are other hotspots of mutation that we
haven't figured out why, yet. Certain mutations occur so often that you have to wonder about a designer. Achondroplastic dwarfism FGFR3
gene has a specific base mutating in this gene in around one in every 10,000 live births. We see this outragous mutation rate because it
produces the dominant dwarf phenotype in humans. Why did the designer stick us with this sequence? It looks like your designer likes
dwarfs. He designed the sequence that has such a high mutation rate, didn't he?

> With this in mind, lets say that a given
> lineage has experienced 10,000 mutations over the course of time (~66
> generations in humans). Of these 10,000 mutations, at least 5,000 of
> them would affect the "junk" DNA. Of the remaining 5,000 mutations,
> only around 200 (2%) of them would affect the protein coding portions
> of the genome. Of these most calculations assume that 10% to 70% are
> functionally neutral. This estimate is based on a detrimental
> mutation rate of 1 to 3 per person per generation with at least some
> scientists (Nachmann and Crowell, 2000) favoring at least 3 or more.30
> Nachmann and Crowell, from the Department of Evolutionary Biology at
> the University of Arizona, suggest that the average per generation
> accumulation of between 1 and 3 detrimental mutations "is likely to be
> biased downward because we have considered only nonsynonymous sites as
> potential targets for deleterious mutations."30 Of course, this means
> that between 30% to 90% (most likely 90%) of mutations affecting
> coding sequences are detrimental.

What is Nachman calling neutral when around 1/3 of the random mutations in coding regions do not change the amino acid sequence, and many
positions swap out similar amino acids between species.

>
>
> Given 10% as the most likely neutral mutation rate estimate for
> mutations involving protein coding genetic sequences, of the 200
> mutations affecting coding regions of DNA, about 180 of them would
> result in a functional change that could be affected by natural
> selection (1.8% of the total number of mutations). Since detrimental
> mutations outnumber beneficial mutations by about 1,000 to 1 (34,36)
> odds are that most if not all 180 mutations would result in a
> selectively detrimental change in function (Only 0.0018% of total
> mutations would be beneficial).

10% is too low for coding sequence.

>
>
> With the rates detailed so far, it would take around 9,700,000
> mutational events to produce just one beneficial mutation in the
> entire protein-coding region of the human genome (~40,000 gene pairs =
> 80,000 genes in a diploid cell). This works out to be around 55,500
> generations to evolve just one beneficial mutation among 80,000 genes.
> Of course, from the perspective of a single gene, this works out to
> be around 4.4 billion generations on average, to get just one
> beneficial mutation. Of course, with a population of one billion,
> there would be two billion copies of this gene. Odds are that at
> least one of these copies will get a beneficial mutation in just two
> or three generations. Of course, then this beneficial mutation will
> increase in the population in proportion to the average reproductive
> rate of the population as well as the reproductive benefit that this
> mutation provides. So, where is the problem?

Think about these numbers, what they tell you is that even with your estimated beneficial mutation rate. One beneficial mutation would
occur each generation in a population of 55,000. This is a new benefit that just adds to the survival of the population. The population
doesn't need this new mutation it is doing just fine without it. So, where is the problem?

>
>
> The problem is that beneficial mutations come at a high cost. The
> reason for this is that every beneficial mutation comes with 1,000 or
> so detrimental mutations. In order for evolution to proceed in a
> positive direction (away from extinction) there must be some way to
> create a favorable balance of beneficial mutations over detrimental
> mutations in a given population. The reason for this is that
> evolution is dependent on mutations as a source of new information.
> If there were no mutations, there would be no evolution. Also, if all
> mutations were negative in a given population (ie: resulting in loss
> of beneficial function), that population would eventually experience
> extinction. Therefore, for a population to live and evolve
> indefinitely, there have to be a few beneficial mutations every now
> and then . . . but how many and how often? What rate and ratio of
> detrimental vs. beneficial mutations is needed to keep a population
> from extinction and yet allow it to evolve and maintain new beneficial
> functions over time?

Actually no beneficial mutations have to happen for the population to not go extinct. Selection only needs to remove the detrimental
mutations . We see this in populations under selection. Detrimental mutations would reach mutation selection balance. A dominant fully
lethal would only be seen in the population at its mutation rate. A recessive partial lethal mutation could reach quite high frequencies in
a population before it reached it could be selected against. New beneficial mutations are only needed for the species to change (evolve).

>
>
> If the average beneficial mutations and detrimental mutations are
> equivalent in their absolute effects on the organism (each one having
> its equivalent on the other side), this would mean that an organism
> with one beneficial and one detrimental mutation would have a neutral
> advantage as far as survival and reproductive fitness. One beneficial
> mutation and two detrimental mutations would have a negative selective
> value for that organism and its offspring. Likewise, two beneficial
> mutations and one detrimental mutation would have a positive selective
> value . . . and so on.

Have you ever heard of genetic load? Populations have a built in genetic load (number of detrimental mutations) that each individual can
tolerate and still maintain a viable population. Just cut to the chase, you have to have some reason to believe that selection could not
select against the detrimental mutations. Your problem is that existing species seem to do just fine some with genetic loads of 15 or
more), so you have no argument.

I'd really like to know where you got this argument because it is the second time that I've seen it.

>
>
> In considering this question further, let's use our above rate of 175
> new mutations per individual (6 billion base pairs) per generation.
> Of these, about 171.997 of them would be selectively neutral and
> approximately 3 would be selectively detrimental, on average. Only
> 0.003 of them would be beneficial. Odds are that an average offspring
> in any given generation will have a selective disadvantage that is
> weighted 1000 to 1 in favor of detrimental over beneficial mutational
> events. What would have to happen to successfully absorb this kind of
> bad Karma?

This must be your own argument because it is so bogus. Why would the addition of 3 more matter when the average person probably inherits
hundreds of old detrimental mutations from their parents in the usual Mendelian style? Do you know what genetic load is. Humans have one
of around 2.5. They think that we are pretty inbred compared to other species (it is probably due to all the cousin matings or worse in
small villages and that genetic bottle neck where we almost went extinct). Other species have genetic loads up to 15. Another way that
people look at this is lethal equivalents. If we were talking about fully recessive lethals humans would have around 5 such alleles in
their genome. They aren't dead because you need to be homozygous to die. The detrimentals that you are talking about are mostly less than
10% lethal. This just means that it would take at least 10 of them to kill you in the homozygous condition. Each human may have hundreds
of slightly detrimental mutations. Three more is nothing.

>
>
> What we really need to do is give the population as a whole a larger
> weight of beneficial over negative mutations. How can this be done?
> What would happen if we had a steady state population of one billion
> individuals? Would this stabilize the population's decline toward
> extinction?

Inbreeding and selection is the best way to reduce the genetic load. If you always outcross your genetic load can get pretty high.

>
>
> With a steady state population of one billion, we would expect around
> 175 billion mutations in our population per generation. Of these,
> around 171.997 billion of them would be neutral, 3 billion of them
> would be detriment, and around 3 million of them would be beneficial
> (1000 to 1 ratio). In this population of one billion, how many of the
> offspring, in a given generation, will have a positive mutational
> balance (ie: more beneficial than detrimental mutations)?

Again it doesn't matter if zero were beneficial. Your only worry is if the population could not support the selection against the
detrimentals, and we have viable populations with a lot higher genetic load than humans.

>

Snip the stuff that doesn't matter about beneficial

>
>
> This does not look very promising for the survival of our population
> much less improved survival. It appears as though the human species
> is devolving, not evolving. There is a steady loss of genetic
> function that is leaving the gene pool far faster than it can be
> replaced by even the potential gains of beneficial mutations. The
> problem is that even if everyone with a detrimental mutational balance
> died without producing offspring, those with a neutral or positive
> mutational balance would have to produce over 20 offspring per person
> (over 40 per female) in order to maintain the population's size and
> avoid extinction. Since this is unlikely, some other process must be
> getting rid of the detrimental mutations faster than they are put into
> the population. Clearly, output of the harmful mutants must be
> greater than their input in order for a population to avoid
> extinction.

>
> Some scientists propose that detrimental mutations are somehow
> concentrated in a small portion of the population via genetic
> recombination.37 Then, when these unfortunate individuals die off
> prematurely, the detrimental mutations leave the population with them.
> How this could be accomplished through naturalistic means is not
> entirely clear. This is the theory, but no one seems able to explain
> how this could even theoretically work in real life.

Who thinks this? Some guys writing in Scientific American? This would be like hoping most of the oxygen in the room congregated in one
corner and all the cretinists start to suffocate. You must have the argument backwards. It is more likely that a subpopulation is isolated
and just by chance it has fewer detrimental mutations and cashes in on this boon by expanding and taking over the range of the larger
population. You know, speciation. How many thousands of subpopulations of white tailed deer are in the Americas, and do they all have the
same genetic backgrounds. Which subpopulation is likley to evolve the next species of deer. The one with the most detrimentals or the
least?

I agree the evidence suggests that there is positive epistasis between deleterious mutations. Do you know what synergistic epistasis
means? The last guy that used this argument didn't know.

> commentary in ëNature' on Eyre-Walker and Keightley's analysis: "Why

> aren't we extinct?"
> Crow's answer is that sex, which shuffles genes around, allows
> detrimental mutations to be eliminated in bunches. The new findings
> thus support the idea that sex evolved because individuals who (thanks
> to sex) inherited several bad mutations rid the gene pool of all of
> them at once, by failing to survive or reproduce.
> Yet natural selection has weakened in human populations with the
> advent of modern medicine, Crow notes. So he theorizes that harmful
> mutations may now be starting to accumulate at an even higher rate,
> with possibly worrisome consequences for health. Keightley is
> skeptical: he thinks that many mildly deleterious mutations have
> already become widespread in human populations through random events
> in evolution and that various adaptations, notably intelligence, have
> more than compensated. "I doubt that we'll have to pay a penalty as
> Crow seems to think," he remarks. 'We've managed perfectly well up
> until now.'"37
>
>
> Even though I do not agree with much of Crow's thinking, I do agree
> with him when he says that harmful mutations are accumulating in the
> human gene pool far faster than they are leaving it. However, on what
> basis does he suggest that harmful mutations spontaneously cluster
> themselves into "bunches" for batch elimination from the gene pool of
> a given population? Crow does not suggest a mechanism nor does it
> seem remotely intuitive as to how this even might occur via
> naturalistic means.

The explanation for the increase is population expansion and relaxed selection constraints. If we still have infant mortality rates as high
as they used to be and our population wasn't expanding would you expect to see this increase?

Only 1/5 to 1/3 of the human conceptions make it to term, and then you have infant mortality. We don't have all the answers, but we do know
that other populations have higher genetic loads than humans do.

We don't have the answers, and you don't either. This could become a problem for us, because it is new ground. Before agriculture the
estimated human population of the world was only in the millions of individuals. In just 10,000 years we have exploded to over 6 billion.
We don't know what effects this will have for the future genetics of the human population. A lot of people are alive that would have died
under the old selection constraints. How our population will adapt to this change is unknown. If you have the answers please present them.

>
>
> Also, Keightley is far too optimistic in my view. He assumes that
> because evolution has happened in the past, that somehow evolution
> will solve the problem. He fails to even consider the notion that
> perhaps humans, apes, and other species with comparably long breeding
> times have been gradually degenerating all along. Perhaps evolution
> only proceeds downhill (devolution)? Perhaps mutations do not improve
> functions over time so much as they remove functions over time in
> species with slow generation times?

We only observe the extant survivors. There have been many species that have gone to extinction for one reason or the other. The vast
majority of extant species will become extinct. Pick the ones that will make it. Apes and a lot of other species may become extinct, but
it isn't due to genetic degeneration. They can't compete with us for a place on this earth. Genetically they probably had a much healthier
genetic population than humans had 10,000 years ago. They have 5 times the genetic variation found in humans even if we outnumber them. If
we were just a speices like chimps they would probably do better than us, but we have brains that they can't match. So we've survived even
with our genetic disadvantages.

>
>
> Then again, even if the degenerative effects of mutations were somehow
> solved in populations with slow reproduction times, the addition of
> new information to the gene pool often involves the crossing of huge
> oceans of neutral/nonfunctional sequence gaps that would take, for all
> practical purposes, forever to cross.41 It seems as though mutations,
> averaged over an extended period of time, tend toward loss and
> extinction rather than toward any sort of improvement or gain.

Detrimental mutations are removed from populations by some mechanism. If this were not true there would be no species left. You keep
forgetting that you have to consider all the data. Life on this planet has a very long history. You can only deny that by making yourself
look like a flat earther. The fact is that species have been around for a very long time and they are still here. Biologist have very
little input into this determination. If you want to argue you will have to argue with the geophysicists and paleontologists. Molecular
biologists will tell you that we see a very long history for many speicies. How long do you think it takes a species to accumulate so much
neutral variation if what you claim is true. A lot of detrimentals would have had to be lost to get the observed ratios of extant
variation. If you want to argue that the earth is not old and that sequences in species look like they have been evolving for a very long
time, do so to our amusement. How old is the earth? What evidence do you have that some designer was maintaining the genetic stability of
populations and just recently decided to take a vacation?

Give the original creationist source for this argument. I'd like to see it.

Ron Okimoto

[Dunno]

In article Sean Pitman wrote:
> The Genetic Degeneration of Humans
>
>

In summary, what did your post say?

[Eric Gill]

Dunno <muen...@hushmail.com> wrote in news:slrnbdkn54.1ru.muenster@old486-
20.hushmail.com:

> In article Sean Pitman wrote:
>> The Genetic Degeneration of Humans
>>
>>
>
> In summary, what did your post say?

"Mutations are always harmful."

[Ron Okimoto]

Netscape line mess up. I have to delete the references because they have very long line lengths.

[Ron Okimoto]

Ron Okimoto wrote:

> Netscape line mess up. I have to delete the references because they have very long line lengths.
>

sorry, somewhere there is a line length that I can't see that is too long. For all I know it is a blank line.

[Ron Okimoto]

seanpi...@naturalselection.0catch.com (Sean Pitman) wrote in message news:<80d0c26f.03060...@posting.google.com>...

> The Genetic Degeneration of Humans
>
> Sean Pitman M.D.
> www.naturalselection.0catch.com
> http://naturalselection.0catch.com/Files/dnamutationrates.html

[One more try to fix the line lengths and then forget it. For some
reason Netscape will not let me put in returns with out puting gaps
between the lines.]

I'd like to read the original creationist source for this post. I
want to compare your version to the original to see if it is you that
is messing up the arguments or the original perpetrator. Where did
you get the citations and the original argument?

Snip:

I'll accept the 175 mutations per generation argument. This isn't a
really high rate. As you know for bacterial work we can get the
mutation rate up to 1 in 10^4-10^5 by just starving the bacteria and
enough of them survive and even adapt to the starvation conditions.
>
>

> important approach to finding them? You absolutely have to go back

> into the lab and get away from the computer terminal."40

They are going to have the chicken genome sequence to compare to the

mammlian sequence and it will be better than the fish sequence in
determining the number of genes in the genome. Can you guess why? We
expect this due to the nature of common descent, you have to claim
that the designer did it that way for some unknown reason when he
didn't have to. What was one of the reasons cited for sequencing the
chicken genome? Why can we predict these things based on evolutionary
relationships, and you have to guess at what your designer might have
done?

> So, it seems as though there is still some question as to exactly how

> many genes the human genome contains. But, for the sake of argument,
> lets go with a lower estimate of ~40,000 genes. With each gene
> averaging 1,350 base pairs in size, only around 108 million base pairs
> out of 6 billion base pairs (diploid) would code for anything. This
> is only around 1.8% of the total genome.
>
> Much of the rest of the human genome (At least 50%) is composed of a
> large amount of "repetitive DNA" that is made up of similar sequences
> occurring over and over.33,38 At least some of the other 48% of the
> genome is thought to provide structural integrity as well as
> regulating the production of the coding sequences of DNA as far as
> when, where, and how much protein to make. However, exactly how much
> of the non-protein-coding genome is functional is not clearly
> understood.

Probably an over estimate.

>
> In any case, since mutations are the only possible source of novel
> genomic function in naturalistic evolution,

No, recombination is a very important tool. You should understand

this because you are claiming that you can use recombination to create
all the various alleles that we see in a given species. It works both
ways, but we have millions of years and you only have a few thousand.
Some genes are over a million base-pairs in length and would have a
recombination event in them about in about 1% of every meiotic event.
Most are much shorter than that (only a few thousand, but the
recombination rate is probably as high as the mutation rate within a
gene.

we should consider a few

> facts about these mutations. Since mutations are thought to be purely
> random events causes by errors of replication and maintenance over
> time, they occur over the entire genome in a fairly random fashion
> with each generation.

They aren't random except in the fact that we can't predict which ones

will happen. We know that transitions (purine to purine or pyrimidine
to pyrimidine) mutations are much more likely at any given position
than are transversions (purine to pyrimidine). We also know that CG
sequences are much more likely to mutate than other sequences. We
also know that there are other hotspots of mutation that we haven't
figured out why, yet. Certain mutations occur so often that you have
to wonder about a designer. Achondroplastic dwarfism FGFR3 gene has a
specific base mutating in this gene in around one in every 10,000 live
births. We see this outragous mutation rate because it produces the
dominant dwarf phenotype in humans. Why did the designer stick us
with this sequence? It looks like your designer likes dwarfs. He
designed the sequence that has such a high mutation rate, didn't he?

With this in mind, lets say that a given

> lineage has experienced 10,000 mutations over the course of time (~66
> generations in humans). Of these 10,000 mutations, at least 5,000 of
> them would affect the "junk" DNA. Of the remaining 5,000 mutations,
> only around 200 (2%) of them would affect the protein coding portions
> of the genome. Of these most calculations assume that 10% to 70% are
> functionally neutral. This estimate is based on a detrimental
> mutation rate of 1 to 3 per person per generation with at least some
> scientists (Nachmann and Crowell, 2000) favoring at least 3 or more.30
> Nachmann and Crowell, from the Department of Evolutionary Biology at
> the University of Arizona, suggest that the average per generation
> accumulation of between 1 and 3 detrimental mutations "is likely to be
> biased downward because we have considered only nonsynonymous sites as
> potential targets for deleterious mutations."30 Of course, this means
> that between 30% to 90% (most likely 90%) of mutations affecting
> coding sequences are detrimental.

What is Nachman calling neutral when around 1/3 of the random

mutations in coding regions do not change the amino acid sequence, and
many positions swap out similar amino acids between species.

>

> Given 10% as the most likely neutral mutation rate estimate for
> mutations involving protein coding genetic sequences, of the 200
> mutations affecting coding regions of DNA, about 180 of them would
> result in a functional change that could be affected by natural
> selection (1.8% of the total number of mutations). Since detrimental
> mutations outnumber beneficial mutations by about 1,000 to 1 (34,36)
> odds are that most if not all 180 mutations would result in a
> selectively detrimental change in function (Only 0.0018% of total
> mutations would be beneficial).

10% is too low for coding sequence.

>

> With the rates detailed so far, it would take around 9,700,000
> mutational events to produce just one beneficial mutation in the
> entire protein-coding region of the human genome (~40,000 gene pairs =
> 80,000 genes in a diploid cell). This works out to be around 55,500
> generations to evolve just one beneficial mutation among 80,000 genes.
> Of course, from the perspective of a single gene, this works out to
> be around 4.4 billion generations on average, to get just one
> beneficial mutation. Of course, with a population of one billion,
> there would be two billion copies of this gene. Odds are that at
> least one of these copies will get a beneficial mutation in just two
> or three generations. Of course, then this beneficial mutation will
> increase in the population in proportion to the average reproductive
> rate of the population as well as the reproductive benefit that this
> mutation provides. So, where is the problem?

Think about these numbers, what they tell you is that even with your

estimated beneficial mutation rate. One beneficial mutation would
occur each generation in a population of 55,000. This is a new
benefit that just adds to the survival of the population. The
population doesn't need this new mutation it is doing just fine

without it. So, where is the problem?

> The problem is that beneficial mutations come at a high cost. The
> reason for this is that every beneficial mutation comes with 1,000 or
> so detrimental mutations. In order for evolution to proceed in a
> positive direction (away from extinction) there must be some way to
> create a favorable balance of beneficial mutations over detrimental
> mutations in a given population. The reason for this is that
> evolution is dependent on mutations as a source of new information.
> If there were no mutations, there would be no evolution. Also, if all
> mutations were negative in a given population (ie: resulting in loss
> of beneficial function), that population would eventually experience
> extinction. Therefore, for a population to live and evolve
> indefinitely, there have to be a few beneficial mutations every now
> and then . . . but how many and how often? What rate and ratio of
> detrimental vs. beneficial mutations is needed to keep a population
> from extinction and yet allow it to evolve and maintain new beneficial
> functions over time?

Actually no beneficial mutations have to happen for the population to

not go extinct. Selection only needs to remove the detrimental
mutations . We see this in populations under selection. Detrimental
mutations would reach mutation selection balance. A dominant fully
lethal would only be seen in the population at its mutation rate. A
recessive partial lethal mutation could reach quite high frequencies

in a population before it reached [a frequency at which] it could be

selected against. New beneficial mutations are only needed for the
species to change (evolve).

>

> If the average beneficial mutations and detrimental mutations are
> equivalent in their absolute effects on the organism (each one having
> its equivalent on the other side), this would mean that an organism
> with one beneficial and one detrimental mutation would have a neutral
> advantage as far as survival and reproductive fitness. One beneficial
> mutation and two detrimental mutations would have a negative selective
> value for that organism and its offspring. Likewise, two beneficial
> mutations and one detrimental mutation would have a positive selective
> value . . . and so on.

Have you ever heard of genetic load? Populations have a built in

genetic load (number of detrimental mutations) that each individual
can tolerate and still maintain a viable population. Just cut to the
chase, you have to have some reason to believe that selection could
not select against the detrimental mutations. Your problem is that
existing species seem to do just fine some with genetic loads of 15 or
more), so you have no argument.

I'd really like to know where you got this argument because it is the
second time that I've seen it.

>

> In considering this question further, let's use our above rate of 175
> new mutations per individual (6 billion base pairs) per generation.
> Of these, about 171.997 of them would be selectively neutral and
> approximately 3 would be selectively detrimental, on average. Only
> 0.003 of them would be beneficial. Odds are that an average offspring
> in any given generation will have a selective disadvantage that is
> weighted 1000 to 1 in favor of detrimental over beneficial mutational
> events. What would have to happen to successfully absorb this kind of
> bad Karma?

This must be your own argument because it is so bogus. Why would the

addition of 3 more matter when the average person probably inherits
hundreds of old detrimental mutations from their parents in the usual
Mendelian style? Do you know what genetic load is. Humans have one
of around 2.5. They think that we are pretty inbred compared to other
species (it is probably due to all the cousin matings or worse in
small villages and that genetic bottle neck where we almost went
extinct). Other species have genetic loads up to 15. Another way
that people look at this is lethal equivalents. If we were talking
about fully recessive lethals humans would have around 5 such alleles
in their genome. They aren't dead because you need to be homozygous
to die. The detrimentals that you are talking about are mostly less
than 10% lethal. This just means that it would take at least 10 of
them to kill you in the homozygous condition. Each human may have
hundreds of slightly detrimental mutations. Three more is nothing.

> What we really need to do is give the population as a whole a larger

> weight of beneficial over negative mutations. How can this be done?
> What would happen if we had a steady state population of one billion
> individuals? Would this stabilize the population's decline toward
> extinction?

Inbreeding and selection is the best way to reduce the genetic load.

If you always outcross your genetic load can get pretty high.

>

> With a steady state population of one billion, we would expect around
> 175 billion mutations in our population per generation. Of these,
> around 171.997 billion of them would be neutral, 3 billion of them
> would be detriment, and around 3 million of them would be beneficial
> (1000 to 1 ratio). In this population of one billion, how many of the
> offspring, in a given generation, will have a positive mutational
> balance (ie: more beneficial than detrimental mutations)?

Again it doesn't matter if zero were beneficial. Your only worry is

if the population could not support the selection against the
detrimentals, and we have viable populations with a lot higher genetic
load than humans.

Snip the stuff that doesn't matter about beneficial

>

> This does not look very promising for the survival of our population
> much less improved survival. It appears as though the human species
> is devolving, not evolving. There is a steady loss of genetic
> function that is leaving the gene pool far faster than it can be
> replaced by even the potential gains of beneficial mutations. The
> problem is that even if everyone with a detrimental mutational balance
> died without producing offspring, those with a neutral or positive
> mutational balance would have to produce over 20 offspring per person
> (over 40 per female) in order to maintain the population's size and
> avoid extinction. Since this is unlikely, some other process must be
> getting rid of the detrimental mutations faster than they are put into
> the population. Clearly, output of the harmful mutants must be
> greater than their input in order for a population to avoid
> extinction.
>
> Some scientists propose that detrimental mutations are somehow
> concentrated in a small portion of the population via genetic
> recombination.37 Then, when these unfortunate individuals die off
> prematurely, the detrimental mutations leave the population with them.
> How this could be accomplished through naturalistic means is not
> entirely clear. This is the theory, but no one seems able to explain
> how this could even theoretically work in real life.

Who thinks this? Some guys writing in Scientific American? This

would be like hoping most of the oxygen in the room congregated in one
corner and all the cretinists start to suffocate. You must have the
argument backwards. It is more likely that a subpopulation is
isolated and just by chance it has fewer detrimental mutations and
cashes in on this boon by expanding and taking over the range of the
larger population. You know, speciation. How many thousands of
subpopulations of white tailed deer are in the Americas, and do they
all have the same genetic backgrounds. Which subpopulation is likley
to evolve the next species of deer. The one with the most
detrimentals or the least?

>

I agree the evidence suggests that there is positive epistasis between

deleterious mutations. Do you know what synergistic epistasis means?
The last guy that used this argument didn't know.

>

> commentary in ?Nature' on Eyre-Walker and Keightley's analysis: "Why

> aren't we extinct?"
> Crow's answer is that sex, which shuffles genes around, allows
> detrimental mutations to be eliminated in bunches. The new findings
> thus support the idea that sex evolved because individuals who (thanks
> to sex) inherited several bad mutations rid the gene pool of all of
> them at once, by failing to survive or reproduce.
> Yet natural selection has weakened in human populations with the
> advent of modern medicine, Crow notes. So he theorizes that harmful
> mutations may now be starting to accumulate at an even higher rate,
> with possibly worrisome consequences for health. Keightley is
> skeptical: he thinks that many mildly deleterious mutations have
> already become widespread in human populations through random events
> in evolution and that various adaptations, notably intelligence, have
> more than compensated. "I doubt that we'll have to pay a penalty as
> Crow seems to think," he remarks. 'We've managed perfectly well up
> until now.'"37
>
>
> Even though I do not agree with much of Crow's thinking, I do agree
> with him when he says that harmful mutations are accumulating in the
> human gene pool far faster than they are leaving it. However, on what
> basis does he suggest that harmful mutations spontaneously cluster
> themselves into "bunches" for batch elimination from the gene pool of
> a given population? Crow does not suggest a mechanism nor does it
> seem remotely intuitive as to how this even might occur via
> naturalistic means.

The explanation for the increase is population expansion and relaxed

selection constraints. If we still have infant mortality rates as
high as they used to be and our population wasn't expanding would you
expect to see this increase?

Only 1/5 to 1/3 of the human conceptions make it to term, and then you
have infant mortality. We don't have all the answers, but we do know
that other populations have higher genetic loads than humans do.

We don't have the answers, and you don't either. This could become a
problem for us, because it is new ground. Before agriculture the
estimated human population of the world was only in the millions of
individuals. In just 10,000 years we have exploded to over 6 billion.
We don't know what effects this will have for the future genetics of
the human population. A lot of people are alive that would have died
under the old selection constraints. How our population will adapt to
this change is unknown. If you have the answers please present them.

>

> Also, Keightley is far too optimistic in my view. He assumes that
> because evolution has happened in the past, that somehow evolution
> will solve the problem. He fails to even consider the notion that
> perhaps humans, apes, and other species with comparably long breeding
> times have been gradually degenerating all along. Perhaps evolution
> only proceeds downhill (devolution)? Perhaps mutations do not improve
> functions over time so much as they remove functions over time in
> species with slow generation times?

We only observe the extant survivors. There have been many species

that have gone to extinction for one reason or the other. The vast
majority of extant species will become extinct. Pick the ones that
will make it. Apes and a lot of other species may become extinct, but
it isn't due to genetic degeneration. They can't compete with us for
a place on this earth. Genetically they probably had a much healthier
genetic population than humans had 10,000 years ago. They have 5
times the genetic variation found in humans even if we outnumber them.
If we were just a speices like chimps they would probably do better
than us, but we have brains that they can't match. So we've survived
even with our genetic disadvantages.

> Then again, even if the degenerative effects of mutations were somehow

> solved in populations with slow reproduction times, the addition of
> new information to the gene pool often involves the crossing of huge
> oceans of neutral/nonfunctional sequence gaps that would take, for all
> practical purposes, forever to cross.41 It seems as though mutations,
> averaged over an extended period of time, tend toward loss and
> extinction rather than toward any sort of improvement or gain.

Detrimental mutations are removed from populations by some mechanism.

If this were not true there would be no species left. You keep
forgetting that you have to consider all the data. Life on this
planet has a very long history. You can only deny that by making
yourself look like a flat earther. The fact is that species have been
around for a very long time and they are still here. Biologist have
very little input into this determination. If you want to argue you
will have to argue with the geophysicists and paleontologists.
Molecular biologists will tell you that we see a very long history for
many speicies. How long do you think it takes a species to accumulate
so much neutral variation if what you claim is true. A lot of
detrimentals would have had to be lost to get the observed ratios of
extant variation. If you want to argue that the earth is not old and
that sequences in species look like they have been evolving for a very
long time, do so to our amusement. How old is the earth? What
evidence do you have that some designer was maintaining the genetic
stability of populations and just recently decided to take a vacation?

Give the original creationist source for this argument. I'd like to
see it.

Ron Okimoto

Snip:

[dave e]

seanpi...@naturalselection.0catch.com (Sean Pitman) wrote in message news:<80d0c26f.03060...@posting.google.com>...

> important approach to finding them? You absolutely have to go back

The first ten paragraphs contained enough nonsense, but number eleven
really takes the cake. Doesn't this author realize that genes
segregate (mostly) independently of one another, and therefore can be
selected independently of one another.

If anyone has bothered to read the remaining 18 paragraphs, please let
me know what they had to say.

Dave

[PTET]

seanpi...@naturalselection.0catch.com (Sean Pitman) wrote in message news:<80d0c26f.03060...@posting.google.com>...

> The Genetic Degeneration of Humans
>

> [snip ridiculous model]

>
> Also, Keightley is far too optimistic in my view. He assumes that
> because evolution has happened in the past, that somehow evolution
> will solve the problem. He fails to even consider the notion that
> perhaps humans, apes, and other species with comparably long breeding
> times have been gradually degenerating all along. Perhaps evolution
> only proceeds downhill (devolution)? Perhaps mutations do not improve
> functions over time so much as they remove functions over time in
> species with slow generation times?
>

> [snip unsupported conclusion]

This sums up Sean's entire post. It's a simple argument from
incredulity.

Sean seems to accept, like Michael Behe, that evolution occurs through
common descent. But they're both unwilling to accept that this happens
by natural means.

We're left with two choices. Either (a) Sean's model is wrong; or (b)
nature is wrong.

As Sean can't provide any evidence whatsoever for his supposed
"devolution", perhaps he should re-examine his basic assumptions ;>

PTET

[Ron Okimoto]

roki...@mail.uark.edu (Ron Okimoto) wrote in message news:<63afe69c.03060...@posting.google.com>...

> seanpi...@naturalselection.0catch.com (Sean Pitman) wrote in message news:<80d0c26f.03060...@posting.google.com>...
> > The Genetic Degeneration of Humans
> >
> > Sean Pitman M.D.
> > www.naturalselection.0catch.com
> > http://naturalselection.0catch.com/Files/dnamutationrates.html
>

Snip:

>
> Detrimental mutations are removed from populations by some mechanism.
> If this were not true there would be no species left. You keep
> forgetting that you have to consider all the data. Life on this
> planet has a very long history. You can only deny that by making
> yourself look like a flat earther. The fact is that species have been
> around for a very long time and they are still here. Biologist have
> very little input into this determination. If you want to argue you
> will have to argue with the geophysicists and paleontologists.
> Molecular biologists will tell you that we see a very long history for
> many speicies. How long do you think it takes a species to accumulate
> so much neutral variation if what you claim is true. A lot of
> detrimentals would have had to be lost to get the observed ratios of
> extant variation. If you want to argue that the earth is not old and
> that sequences in species look like they have been evolving for a very
> long time, do so to our amusement. How old is the earth? What
> evidence do you have that some designer was maintaining the genetic
> stability of populations and just recently decided to take a vacation?
>
> Give the original creationist source for this argument. I'd like to
> see it.
>
> Ron Okimoto
>
> Snip:

I meant to give the molecular reasoning for why we know that the
detrimentals are being taken out of the population. If you look at
the sequence variation between various alleles of a given gene you see
a ratio of more silent substitutions to replacement substitutions.
This is usually a ratio of 2:1 or or so. If all sites were equally
likely to be hit we would expect the exact opposite ratio, if these
replacement substitutions were not being eliminated from the
population. This just means that we should see 2 replacement
mutations for every silent mutation, but we see the opposite. This
tells us that most of the mutations in coding regions are taken out of
the population by selection. If selection were as bad as Sean claims
in removing these mutations we should still see them in the extant
population. Why don't we see the replacement substitutions if the
population should have become extinct trying to remove them? Most
humans do not come close to having 40 offspring and yet humans are
still here and a whole bunch of mutations that must have happened
aren't. It could just be that the designer likes silent mutations and
he made sure that Noah and his family had more than their share, but
he would have to do this for all the species on the Ark.

Ron Okimoto

[Sean Pitman]

Ron Okimoto

> I'd like to read the original creationist source for this post. I
> want to compare your version to the original to see if it is you that
> is messing up the arguments or the original perpetrator. Where did
> you get the citations and the original argument?

This is the original paper. I came up with the idea for the argument
myself, did the research myself, read the articles myself (not just
the abstracts like you), and wrote the paper myself. After writing
the paper, I did get some helpful input and general proof reading from
Dr. Anthony Zuccarelli (Ph.D. in biophysics from the California
Institute of Technology) who agreed with my calculations and
conclusions. I'm sorry to disappoint you, but other than the help of
Dr. Z, no other help was given and no "creationist papers" were used
as references or sources of "inspiration".

In any case, I'm glad that at least your are capable of accepting some
things as problems for your position. Of course, since you "know"
that evolution is true, such problems really must have answers
somewhere. They really can't be all that significant, because you
know from all the other evidence that finding a naturalistic answer to
this particular problem is certainly just a matter of time.

Until then, I really do admire your faith. . .

Sean

[Jeff Stubbs]

In article <80d0c26f.03060...@posting.google.com>, Sean
Pitman <seanpi...@naturalselection.0catch.com> wrote:

<snip>

>
> In any case, I'm glad that at least your are capable of accepting some
> things as problems for your position. Of course, since you "know"
> that evolution is true, such problems really must have answers
> somewhere. They really can't be all that significant, because you
> know from all the other evidence that finding a naturalistic answer to
> this particular problem is certainly just a matter of time.
>
> Until then, I really do admire your faith. . .
>

This discussion is out my ken, so I'll leave it to more qualified
individuals to reply. But the last paragraph and, especially, the last
line is puzzling. Is the good doctor sinking to the level of common
creationists? In my initial reading of the above quoted text, he seems
to be implying that the acceptance of the process of evolution as an
explanation of life's diversity is a "religion". Did I get it wrong?

I sure hope that isn't the case. I really resent the implication by the
Discovery Institute and others, that without the belief in a
supernatural deity, the unwashed masses (such as myself) can't be
expected to live a moral or socially responsible life.

Say ain't so, Doc

Jeff

--
People who want to share their religious views with you
almost never want you to share yours with them.

[John Wilkins]

Sean Pitman <seanpi...@naturalselection.0catch.com> wrote:

In which case, Sean, kudos for doing the work even if, as more
experienced posters like Ian argue, you do not really understand the
sources you cite.
--
John Wilkins
"And this is a damnable doctrine" - Charles Darwin, Autobiography

[Pokemoto]

>Subject: Re: The Genetic Degeneration of Humans
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>From: seanpi...@naturalselection.0catch.com (Sean Pitman)
>Newsgroups: talk.origins
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Give it up Sean, you are going down into places that you don't want to go.
Dishonesty is the heart of corruption for creationism. If it wasn't
creationism wouldn't look so pathetic.

Take the fact that we observe that over half the mutations are missing to your
Dr. Z and see if he can put that fact in your model and make your argument
work. Why are there too many silent substitutions in genes if the replacement
substitutions haven't been selected against and removed from the population?
Even without all my other arguments against your degeneration argument this
alone should make you think twice. If it would really take 40 offspring to
enable selection against detrimental mutations how did we get rid of over half
of the total mutations? Not only that but a lot of the remaining mutations are
being selected against, they just have a lower selection value and can float in
the population at a higher frequency than the more detrimental mutations.

Why would your designer put too many silent substitutions in genes? How were
all these replacement mutations removed from the population if your argument is
correct? We have this data.

For science it doesn't take any more faith than you use to get up and brush
your teeth in the morning, while your clinging to your bankrupt arguments takes
a faith of a very different nature. Some would call it insanity.

Science doesn't know everything, your problem is that we know enough to make
your arguments look bogus.

I went to the web page you list in the first post in this thread, and I was
really disappointed. Your mitochondrial argument is as dishonest as any that
I've ever seen. You are either stupid or dishonest. Since you keep citing the
Neandertal data I can only conclude that dishonesty has a lot to do with it. I
can't see a way that you can make the blunders that you do and still claim to
have read any mito papers more recent than the early 1990's.

Read this recent review and get an idea of why your mitochondrial arguments are
as bogus as they can possibly be (Cavalli-Sforza and Feldman, 2003. The
application of molecular genetic approaches to the study of human evolution.
Nature Genetics Supplement Vol. 33 pp. 266-275).

In this reference you will find out that the Cann and Wilson paper was
vindicated by later research. We all laughed when we found out that the Wilson
group didn't follow the directions on the software package, but the data was
robust enough to give them essentially the correct result. It was the largest
data set of its kind at the time. Their results were confirmed by many later
studies. Everything you hope to gain by using this paper the way you do is
just sad. What does it matter if they made some mistakes if the conclusions of
their paper were essentially correct?

Do a Citation Index search using the Parson, 1997 paper that you use. You will
find that not a single researcher could reproduce these results. This is why
the Cavalli-Sforza and Feldman paper doesn't even cite this paper. It is
unconfirmed and not reproducable. It is a common type of paper you run into.
It sounds interesting, a lot of researchers check it out and they find that
they can't get the same results. Since you base nearly the entire mito section
on misrepresenting these two papers, what do you think that you should do about
it? What would an honest person do? How could you ignore a decade of research
in one case and half a decade of research in the other case?

Stop this stupid act. You almost make me believe that Nowhere Man was your
sock puppet, you are starting to act more and more like him. Just think of how
bad Nowhere Man looks, and then look at yourself. You claim responsiblity for
producing the dishonest material that ignorant guys like Nowhere and Zoe get
sucked in by. In this case there seems to be a "degenerations of humans," but
you will have to demonstrate that it has anything to do with genetics.

Ron Okimoto

[Mitchell Coffey]

Look, you pretty much lifted your Mendel discussion from an article on
a Dutch website. In the process you picked up that site's ridiculous
equation of mutation with inheritance of acquired characteristics. I
can't blame him for supposing there's some ur-text out there for your
argument-from-personal-incredulity.

Mitchell Coffey

[Howard Hershey]

in article 80d0c26f.03060...@posting.google.com, Sean Pitman at
seanpi...@naturalselection.0catch.com wrote on 6/1/03 2:49 PM:

> The Genetic Degeneration of Humans
>
> Sean Pitman M.D.
> www.naturalselection.0catch.com
> http://naturalselection.0catch.com/Files/dnamutationrates.html
>
>

[snip]

> With this in mind, lets say that a given
> lineage has experienced 10,000 mutations over the course of time (~66
> generations in humans). Of these 10,000 mutations, at least 5,000 of
> them would affect the "junk" DNA. Of the remaining 5,000 mutations,
> only around 200 (2%) of them would affect the protein coding portions
> of the genome. Of these most calculations assume that 10% to 70% are
> functionally neutral.

And where does this 10% to 70% estimate come from? [10% is obviously too
low, given the expected neutrality of changes in the third (and sometimes
second) nucleotide of the triplet code, because of degeneracy.]

> This estimate is based on a detrimental
> mutation rate of 1 to 3 per person per generation with at least some
> scientists (Nachmann and Crowell, 2000) favoring at least 3 or more.30

Notice that this is directly the value of detrimental mutations per
generation. That means that they expect 1 to 3 *detrimental* mutations per
generation. *If* you are correct that there are about 200 mutations per
generation in coding sequences, that implies that only 0.5-1.5% of mutations
in coding sequences are *detrimental*. That's why I asked how you got the
estimate that 10-70% of mutations are functionally neutral? That would
mean, since only 1-3 of those 200 mutations are detrimental and *only*
10-70% are neutral, that a huge fraction of mutations are beneficial.
Frankly, I don't believe that and I strongly doubt that you do, either. So
something is wrong here in your calculation or in Nachmann and Crowell's
estimate of *deleteriousness*.

> Nachmann and Crowell, from the Department of Evolutionary Biology at
> the University of Arizona, suggest that the average per generation
> accumulation of between 1 and 3 detrimental mutations "is likely to be
> biased downward because we have considered only nonsynonymous sites as
> potential targets for deleterious mutations."30 Of course, this means
> that between 30% to 90% (most likely 90%) of mutations affecting
> coding sequences are detrimental.
>
> Given 10% as the most likely neutral mutation rate estimate for
> mutations involving protein coding genetic sequences,

Given the frequency of absolutely synonymous changes (mutations that produce
the same amino acid at the same position), especially if you remember the
higher frequency of transitions to transversions in point mutations, this is
clearly a gross underestimate.

> of the 200
> mutations affecting coding regions of DNA, about 180 of them would
> result in a functional change that could be affected by natural
> selection (1.8% of the total number of mutations). Since detrimental
> mutations outnumber beneficial mutations by about 1,000 to 1 (34,36)
> odds are that most if not all 180 mutations would result in a
> selectively detrimental change in function (Only 0.0018% of total
> mutations would be beneficial).

And that number disagrees with Nachmann and Crowell's estimate by a factor
of 100. Can you detail the basis for the discrepancy? Citing David
Plaisted's site is not evidence. He is not a scientist working in the field
of genetics. He is a creationist apologist. You need to cite (and *read*)
the articles that he uses to generate this number.
>
[snip]

>
> The problem is that beneficial mutations come at a high cost. The
> reason for this is that every beneficial mutation comes with 1,000 or
> so detrimental mutations.

I agree that one must be able to selectively remove about 1-3 deleterious
mutations (on average) per individual per generation. Fortunately, genetic
systems are somewhat forgiving, but also quite brutal. One way to remove
them is to do so early. And, in fact, early death of embryos is quite
common in even organisms like humans that have few offspring and expend a
lot of energy to care for them. What is the ratio of spontaneous abortions
that are detectable -- and there are probably at least an equal number that
occur before the state of detectability -- to live births, Herr Doktor? And
what is the average number of lethal alleles that the average person has (in
the recessive state, of course)?

[snip]

>
> If the average beneficial mutations and detrimental mutations are
> equivalent in their absolute effects on the organism (each one having
> its equivalent on the other side), this would mean that an organism
> with one beneficial and one detrimental mutation would have a neutral
> advantage as far as survival and reproductive fitness. One beneficial
> mutation and two detrimental mutations would have a negative selective
> value for that organism and its offspring. Likewise, two beneficial
> mutations and one detrimental mutation would have a positive selective
> value . . . and so on.

And where did you learn genetics? The above has nothing to do with how
alleles produce function. Besides, as you might notice, beneficial and
detrimental are adjectives to describe mutation. They are conditional
adjectives dependent upon environment, not inherent properties.

>
> In considering this question further, let's use our above rate of 175
> new mutations per individual (6 billion base pairs) per generation.
> Of these, about 171.997 of them would be selectively neutral and
> approximately 3 would be selectively detrimental, on average. Only
> 0.003 of them would be beneficial. Odds are that an average offspring
> in any given generation will have a selective disadvantage that is
> weighted 1000 to 1 in favor of detrimental over beneficial mutational
> events. What would have to happen to successfully absorb this kind of
> bad Karma?

Early death. Often and frquently. Most often even before birth. God must
love abortions, since he performs so many of them. (That was a joke about a
reality of life and should not be taken as pro- or anti- human-induced
abortions.)

>
> What we really need to do is give the population as a whole a larger
> weight of beneficial over negative mutations. How can this be done?
> What would happen if we had a steady state population of one billion
> individuals? Would this stabilize the population's decline toward
> extinction?

Not unless you have a mechanism for removal of the 1-3 deleterious mutations
that form anew each generation. Early death (especially of the unlucky tail
of the Poisson distribution of such traits) is the current mechanism life
uses to accomplish this. And enforcing a stable population would have
absolutely no effect on the amount of "natural" removal unless you also use
this population set point specifically and artificially cull out what you
would regard as the "defectives" from the population that lead to an
excessively larger population growth. Can you think of an alternative
mechanism?
>
[more GIGO numbers that confuses the issue by somehow thinking that
mutations are beneficial or detrimental as an inherent property and that
ignores the natural spread of mutations that are 'beneficial' in a
particular environment]

>
> This does not look very promising for the survival of our population
> much less improved survival. It appears as though the human species
> is devolving, not evolving. There is a steady loss of genetic
> function that is leaving the gene pool far faster than it can be
> replaced by even the potential gains of beneficial mutations.

> The
> problem is that even if everyone with a detrimental mutational balance
> died without producing offspring, those with a neutral or positive
> mutational balance would have to produce over 20 offspring per person
> (over 40 per female) in order to maintain the population's size and
> avoid extinction. Since this is unlikely, some other process must be
> getting rid of the detrimental mutations faster than they are put into
> the population. Clearly, output of the harmful mutants must be
> greater than their input in order for a population to avoid
> extinction.
>
> Some scientists propose that detrimental mutations are somehow
> concentrated in a small portion of the population via genetic
> recombination.37 Then, when these unfortunate individuals die off
> prematurely, the detrimental mutations leave the population with them.
> How this could be accomplished through naturalistic means is not
> entirely clear. This is the theory, but no one seems able to explain
> how this could even theoretically work in real life.

The distribution of detrimental mutations per individual is in a Poisson
distribution (not every individual has exactly the average number of
deleterious mutations). If the average number of deleterious mutations
(from a parent with an average of 2, which is half way between 1-3) passed
on per individual gamete were 1, then, by chance, about 36% of gametes would
have none, 36% would have 1, and the remainder would have 2 or more.

>
> Nachmann and Crowell detail the perplexing situation at hand in the
> following conclusion from their fairly recent paper on human mutation
> rates:
>
>
> "The high deleterious mutation rate in humans presents a paradox. If
> mutations interact multiplicatively, the genetic load associated with
> such a high U [detrimental mutation rate] would be intolerable in
> species with a low rate of reproduction [like humans and apes etc.] .
> . .
> 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.

Specifically, she would need to produce 40 zygotes which are then tested by
selection during development in order for selection to find 2 that survive.
But this would be better tested in birds than in humans, because the
frequency of dud eggs would be a better estimate. Given that the % of dud
eggs is smaller than would be required (it is not zero, but it is also not
95%), it is likely that some other mechanism is involved.

> 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 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; this is, if each additional
> mutation leads to a larger decrease in relative fitness. 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 death of all those with a detrimental
> mutational balance], the results presented here indicate that some
> form of positive epistasis among deleterious mutations is likely."30

And truncation selection might well be the answer. And remember that, for
most new mutations, recessiveness to the normal allele is the norm. And
most new mutations, whether detrimental, beneficial, or neutral, removal by
chance alone is the usual fate.

>
>
> Nachmann and Crowell find the situation a very puzzling one. How does
> one get rid of all the bad mutations faster than they are produced?
> Does their hypothesis of "positive epistasis" adequately explain how
> detrimental mutations can be cleared faster than they are added to a
> population?

They do not need to be cleared *faster* than they are added. They only need
to be cleared *as fast* as they are added. It is most likely that this
equilibrium state is only altered by a change in environment which changes
the beneficial/detrimental/neutral status of pre-existing alleles.

> If the functional effects of mutations were increased in
> a multiplicative instead of additive fashion, would fewer individuals
> die than before?

Fewer would have to die to remove the same number of deleterious alleles
that have a functional effect. But I think that most new deleterious
alleles act like effectively neutral alleles (being recessive wrt
phenotype). That means that most are removed by chance alone within at most
a few generations, just as neutral alleles are. *If*, by chance, the
frequency of a deleterious allele rises to the point where you have
significant numbers of individuals being born homozygous (exhibiting the
deleterious phenotype), then selection comes into play. Such deleterious
alleles can never rise to the point where they are present in most of the
population. The *maximum* frequency of such alleles (*all* such alleles
that cause a particular deleterious phenotype in the homozygous state) is
determined by the selective disadvantage of the homozygote. The frequency
of such alleles *can*, however, drift well below this maximum by chance
alone. Selection sets a ceiling for particular phenotypes. Drift sets the
minimum at complete loss of any particular allele. For neutral and
beneficial mutations, the maximum is fixation and the minimum is loss.

[snip]

> However, without
> getting rid of the accumulating deleterious mutations, the population
> would eventually find itself experiencing an exponential rise in its
> death rate as its average population crossed the line of lethal
> mutations.

Selection sets the maximum frequency of *all* the deleterious alleles in a
population that, in the homozygous state usually, produce a deleterious
phenotype. Drift determines the lower bound, which is complete loss.

> Since the theory of positive epistasis does not seem to help the
> situation much, some other process must be found to explain how to
> preferentially get rid of detrimental mutations from a population.
> Consider an excerpt from a fairly recent Scientific American article
> entitled, "The Degeneration of Man" :
>
>
> "According to standard population genetics theory, the figure of three
> harmful mutations per person per generation implies that three people
> would have to die prematurely in each generation (or fail to
> reproduce) for each person who reproduced in order to eliminate the
> now absent deleterious mutations [75% death rate]. Humans do not
> reproduce fast enough to support such a huge death toll. As James F.
> Crow of the University of Wisconsin asked rhetorically, in a
> commentary in ‘Nature' on Eyre-Walker and Keightley's analysis: "Why
> aren't we extinct?"
> Crow's answer is that sex, which shuffles genes around, allows
> detrimental mutations to be eliminated in bunches. The new findings
> thus support the idea that sex evolved because individuals who (thanks
> to sex) inherited several bad mutations rid the gene pool of all of
> them at once, by failing to survive or reproduce.

Remember that "person" should be read as zygote. But I agree that 75% is
probably too high. Sex, as Crow notes, produces the Poisson distributions
of deleteriousness of which I spoke.

> Yet natural selection has weakened in human populations with the
> advent of modern medicine, Crow notes. So he theorizes that harmful
> mutations may now be starting to accumulate at an even higher rate,
> with possibly worrisome consequences for health. Keightley is
> skeptical: he thinks that many mildly deleterious mutations have
> already become widespread in human populations through random events
> in evolution and that various adaptations, notably intelligence, have
> more than compensated. "I doubt that we'll have to pay a penalty as
> Crow seems to think," he remarks. 'We've managed perfectly well up
> until now.'"37
>
>
> Even though I do not agree with much of Crow's thinking, I do agree
> with him when he says that harmful mutations are accumulating in the
> human gene pool far faster than they are leaving it.

Except he doesn't say that. He says the exact opposite. He points out that
*the fact of nature is* that we do NOT see harmful mutations accumulating in
the human gene pool far faster than they are leaving it. Since our theories
and estimates of the the frequency of mutation, taken simplistically, imply
that we should be seeing that, our simplistic explanations are wrong. Note
that he explicitly rejects the idea that reality is wrong and the theory is
right (unlike what you are doing). Even if Crow's explanation is wrong,
that will not change the *reality* that harmful mutations are NOT

accumulating in the human gene pool far faster than they are leaving it.

You cannot change reality by pointing out that theory says reality should be
different than it is.

> However, on what
> basis does he suggest that harmful mutations spontaneously cluster
> themselves into "bunches" for batch elimination from the gene pool of
> a given population? Crow does not suggest a mechanism nor does it
> seem remotely intuitive as to how this even might occur via
> naturalistic means.
>
> Also, Keightley is far too optimistic in my view. He assumes that
> because evolution has happened in the past, that somehow evolution
> will solve the problem. He fails to even consider the notion that
> perhaps humans, apes, and other species with comparably long breeding
> times have been gradually degenerating all along. Perhaps evolution
> only proceeds downhill (devolution)? Perhaps mutations do not improve
> functions over time so much as they remove functions over time in
> species with slow generation times?
>
> Then again, even if the degenerative effects of mutations were somehow
> solved in populations with slow reproduction times, the addition of
> new information to the gene pool often involves the crossing of huge
> oceans of neutral/nonfunctional sequence gaps that would take, for all
> practical purposes, forever to cross.41

You keep confusing the terms "neutral" and "nonfunctional". Your idea of
evolution as arch formation where parts or changes are assembled or
accumulated without any effect or useful function until a capstone mutation
which poofs function into existence is what is an absurd strawman.

[Steve Schaffner]

Howard Hershey <hers...@indiana.edu> writes:

> > This estimate is based on a detrimental
> > mutation rate of 1 to 3 per person per generation with at least some
> > scientists (Nachmann and Crowell, 2000) favoring at least 3 or more.30
>
> Notice that this is directly the value of detrimental mutations per
> generation. That means that they expect 1 to 3 *detrimental* mutations per
> generation.

Has anyone pointed out yet that Nachman (one "n") and Crowell's
estimate assumes 70,000 genes in the human genome, and is therefore at
least a factor of two too high? I suspect their mutation rate is also
too high: it depends both on the time since chimp/human divergence and
on the ancestral population size, and I find values near the upper end
of their ranges for both parameters most plausible. I wouldn't be at
all surprised if the actual rate of detrimental mutations turns out to
be less than 1 per generation.

[...]

> > 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.
>
> Specifically, she would need to produce 40 zygotes which are then tested by
> selection during development in order for selection to find 2 that survive.

Actually 40 gametes -- some mutations must be lethal at the level of
sperm or egg, and don't contribute at all to genetic load. (I have no
idea what fraction it is.)

--
Steve Schaffner s...@genome.wi.mit.edu
Immediate assurance is an excellent sign of probable lack of
insight into the topic. Josiah Royce

[Tim Tyler]

Sean Pitman <seanpi...@naturalselection.0catch.com> wrote:

: The Genetic Degeneration of Humans

: Sean Pitman M.D.
: www.naturalselection.0catch.com
: http://naturalselection.0catch.com/Files/dnamutationrates.html

[...]

: Keightley is far too optimistic in my view. He assumes that because

: evolution has happened in the past, that somehow evolution will solve
: the problem. He fails to even consider the notion that perhaps humans,
: apes, and other species with comparably long breeding times have been
: gradually degenerating all along. Perhaps evolution only proceeds
: downhill (devolution)? Perhaps mutations do not improve functions over
: time so much as they remove functions over time in species with slow
: generation times?

Obviously evolution made humans out of chimpanzee relatives. If
evolution can do thet using only "downhill" mutations - then
long live devolution.

The modern rate of mutation in humans may indeed cause some problems in
the long term.

W. D. Hamilton also thinks it's a cause for concern (in vol. 1 of his
collected papers).

No doubt modern medicine will come to the rescue - with the ability
to compensate for many problems - and selectively abort any "bad"
offspring that don't do themselves in.
--
__________
|im |yler http://timtyler.org/ t...@tt1.org