Experimental basis for the Non-Beneficial Gap Problem

On Jul 4, 8:54 pm, John Harshman <jharshman.diespam...@xxxxxxxxxxx>
wrote:
Seanpit wrote:
On Jun 20, 6:53 am, John Harshman <jharshman.diespam...@xxxxxxxxxxx>
wrote:

How can you know any of this? What evidence do you have?

There is a great deal of evidence to overwhelmingly suggest that a
functionally beneficial CytoC protein cannot be produced with any
arrangement of just 20aa. Do you honestly think this is even a remote
possibility from the perspective of any living thing? If so, please
do present your counter argument here.

It does seem unlikely. But I would be interested to know what the great
deal of evidence is that you have here. Simply saying that there is a
great deal of evidence is not evidence, you know.

Do you not remember the many times I've listed the papers by Yockey,
Sauer and Olsen in this forum dealing with this topic?

Do you know how many residues in CytoC are "invariant"? Partially
variant? Some suggest that between 27 and 29 amino acid residue
positions are invariant due to "biological requirements" (
http://www.springerlink.com/content/p840152h37w487uj/ ). This would
strongly suggest that the minimum size requirement cannot be less than
the invariant residue requirement for the CytoC function. Beyond
this, many other positions are very restricted to only two or three
residue options. Only a few positions are widely variant between more
than 8 or 9 residues and these are usually restricted to certain types
of residues (i.e., polar vs. non-polar). This raises the likely
minimum size requirement even further to well over 50aa positions at
minimum for the CytoC function (more like 80aa, but you get the point
of the argument).

Authors like Yockey and Sauer and Olsen use this same sort of thinking
to calculate their own rough estimates of ratios of sequences that
carry certain functions.

It seems that in 1978 Yockey calculated the ratio of cytochrome c
sequences in sequence space via phylogenetic sequence comparisons and
then published an article in the Journal of Theoretical Biology
(Yockey, 1981, J Theor Biol, 91) suggesting that the ratio of
functional cytochrome c sequences in sequence space of about 100aa
would probably be around 1 in 1e65.

In this light, it is interesting to consider the work of "Robert T.
Sauer and his M.I.T. team of biologists who undertook the scientific
research of substituting the 20 different types amino acids in two
different proteins. After each substitution, the protein sequence was
reinserted into bacteria to be tested for function. They discovered
that in some locations of the protein's amino acid chains, up to 15
different amino acids may be substituted while at other locations
their was a tolerance of only a few, and yet other locations could not
tolerate even one substitution of any other amino acid. One of the
proteins they chose was the 92-residue lambda repressor.

Sauer et. al. calculated that:

"... there should be about 10^57 different allowed sequences for the
entire 92 residue domain. ... the calculation does indicate in a
qualitative way the tremendous degeneracy in the information that does
specifies a particular protein fold. Nevertheless, the estimated
number of sequences capable of adopting the lambda repressor fold is
still an exceedingly small fraction, about 1 in 10^63, of the total
possible 92 residue sequences." Sauer et. al. go on to highlight that
Yockey (1978) had obtained similar result for cytochrome C."

"Sauer's results in particular can be used to calculate the
probability of finding a given protein structure. Proceed in the
following manner. If any of ten amino acids can appear in the first
position of a given functional protein sequence then the odds are 1 in
2 that a nondirected search will place one of the allowed group there.
If any of four amino acids can appear in the second position then the
odds are 1 in 5 of finding one of that group, and the odds of finding
the correct amino acids next to each other in the first two positions
are one-half times one-fifth, which is one-tenth. Suppose in the third
position there is an absolute requirement for G. Then the odds of
getting a G at that position are one in twenty and the odds of getting
the first three amino acids right are now up to one in two hundred. In
this aspect it is like winning a trifecta in horse racing. Over the
course of 100 amino acids in our small protein the odds quickly reach
astronomical numbers.

From the actual experimental results of Sauer's group it can easily be
calculated that the odds of finding a folded protein are about 1 in 10
to the 65 power. To put this fantastic number in perspective imagine
that someone hid a grain of sand, marked with a tiny 'X', somewhere in
the Sahara Desert. After wandering blindfolded for several years in
the desert you reach down, pick up a grain of sand, take off your
blindfold, and find it has a tiny 'X'. Suspicious, you give the grain
of sand to someone to hide again, again you wander blindfolded into
the desert, bend down, and the grain you pick up again has an 'X'. A
third time you repeat this action and a third time you find the marked
grain. The odds of finding that marked grain of sand in the Sahara
Desert three times in a row are about the same as finding one new
functional protein structure. Rather than accept the result as a lucky
coincidence, most people would be certain that the game had been
fixed.

The number of 1 in 10^65, arrived at by Sauer's experimental route, is
virtually identical to the results obtained by Yockey's theoretical
calculation and his deduction from natural cytochrome c sequences! It
therefore strongly reinforces our confidence that a correct result has
been obtained. Sauer's group obtained closely similar results for two
different proteins: arc repressor and lamda repressor. This means that
all proteins that have been examined to date, either experimentally or
by comparison of analogous sequences from different species, have been
seen to be surrounded by an almost infinitely wide chasm of unfolded,
nonfunctional, useless protein sequences. There are no ledges, no
buttes, no stepping stones to cross the chasm. The conclusion that a
reasonable person draws from this is that the laws of nature are
insufficient to produce functional proteins and, therefore, functional
proteins have not been produced through a nondirected
search." ( http://www.arn.org/docs/behe/mb_smu1992.htm )


1. Yockey, H.P. Information Theory and Molecular Biology. Cambridge
University Press, 1992. pp. 255, 257.
2. Yockey, H. P. "Self Organization Origin of Life Scenarios and
Information Theory", Journal of Theoretical Biology (1981) 91, 13-31.
3. Yockey, H. P. "A Calculation of the Probability of Spontaneous
Biogenesis by Information Theory", Journal of Theoretical Biology
(1978) 67, 377-398.
4. Yockey, H.P., On the information content of cytochrome C, Journal
of Theoretical Biology , 67 (1977), p. 345-376.
5. Bowie, J. U., & Sauer, R. T. (1989) "Identifying Determinants of
Folding and Activity for a Protein of Unknown Structure", Proceedings
of the National Academy of Sciences USA 86, 2152-2156.
6. Bowie, J. U., Reidhaar-Olson, J. F., Lim, W. A., & Sauer, R. T.
(1990) "Deciphering the Message in Protein Sequences: Tolerance to
Amino Acid Substitution", Science 247, 1306-1310.
7. Reidhaar-Olson, J. F., & Sauer, R. T. (1990) "Functionally
Acceptable Substitutions in Two -Helical Regions of Repressor",
Proteins: Structure, Function, and Genetics 7, 306-316.
8. R.T. Sauer, James U Bowie, John F.R. Olson, and Wendall A. Lim,
1989, 'Proceedings of the National Academy of Science's USA 86,
2152-2156. and 1990, March 16, Science, 247; and, Olson and R.T.
Sauer, 'Proteins: Structure, Function and Genetics', 7:306 - 316,
1990.

http://www.arn.org/docs/behe/mb_smu1992.htm



You see, there is a spectrum of certainty. Given 100aa size limit, it
is absolutely certain that a CytoC protein can be produced. Reduce
this limit to 80aa, and it is still possible; keep going down to 70aa,
and it becomes less likely; down to 50aa and it becomes unlikely; down
to 30-40aa and it becomes very very unlikely; down to 20aa and it
becomes downright unbelievable; down to 10aa absolutely impossible.

I would be interested to know how you arrived at even these vague limits.

See above . . .

The very same thing is true of all functionally beneficial biosystems,
except that the likely limitations change. For example, do you
honestly think you could build a functionally beneficial rotary
flagellar motility system with a limit of only 1,000 coded amino acid
residue positions? Think again . . .

I have no idea. How did you decide that you couldn't? Does it involve
exproctoducation?

Do you think Yockey, Sauer and Olsen pulled their estimates out of
their arses? Hmmmmm? Their methods can be used to get a useful
approximation for many protein-based systems of function - to include
multiprotein systems that require all their protein parts to be
specifically arranged with each other in space to work to produce the
function in question (such as the flagellar motility system).

Beyond this, if you have no such estimates to support your own
position, you really don't have a scientific basis for your beliefs
when it comes to the creative potential of the mechanism of random
mutation and natural selection. All you really have is blind faith -
wishful thinking at best. That's not science.

Sean Pitman
www.DetectingDesign.com

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