Impossible evolution of new beneficial proteins

If you are saying that beneficial mutations don't exist, then you are completely wrong. In this abstract, hemoglobin C confers resistance to malaria (hemoglobin C is mutatated hemoglobin A).;-------------------
Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack.Rihet P, Flori L, Tall F, Traore AS, Fumoux F.Universite de la Mediterranee, IFR48, Faculte de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. rihet@luminy.univ-mrs.frGenetic predisposition to malaria has been shown by epidemiological, case-control and linkage studies. In particular, case-control studies have recently shown association between hemoglobin C and resistance to severe malaria in Mali and to clinical malaria in Burkina Faso. In a longitudinal study of families living in an endemic area, we investigated whether hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. We surveyed 256 individuals (71 parents and 185 sibs) from 53 families during 2 years. Hemoglobin C carriers had less frequent malaria attacks than AA individuals within the same age group (P=0.01). Since age correlated with malaria attack and parasitemia (P<0.0001), we took age into account in association analyses. We performed combined linkage and association analyses, which avoid biases due to population structure. Using multi-allelic tests, we evidenced association between hemoglobin genotype and phenotypes related to malarial infection and disease (P<0.001). We further analyzed individual hemoglobin alleles and detected negative association between hemoglobin C and malaria attack (P=0.00013). Analyses that took into account confounding factors confirmed the negative association of hemoglobin C with malaria attack (P=0.0074) and evidenced a negative correlation between hemoglobin C and parasitemia (P=0.0009). These associations indicate that hemoglobin C reduces parasitemia and confers protection against mild malaria attack.
-------------------If you are saying that amino acid sequence can not be rearranged or truncated without losing function then you are incorrect as well. My own work (being sent to press as of this moment) deals with proteolytic cleavage of a bacterial enzyme. The enzyme does not decrease in activity, specificty, or rate of reaction even though 40% of its amino acids are cleaved off. As soon as it is accepted for print I will post the abstract. However, there are numerous examples of just this phenomena in the literature which can be found at http://www.pubmed.comSecondly, amino acid sequences are not statistically signifigant (ie, they appear to be random), as can be seen in this abstract:
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Information content of protein sequences.Weiss O, Jimenez-Montano MA, Herzel H.Institute for Theoretical Biology, Humboldt University Berlin, Invalidenstr. 43, Berlin, D-10115, Germany.The complexity of large sets of non-redundant protein sequences is measured. This is done by estimating the Shannon entropy as well as applying compression algorithms to estimate the algorithmic complexity. The estimators are also applied to randomly generated surrogates of the protein data. Our results show that proteins are fairly close to random sequences. The entropy reduction due to correlations is only about 1%. However, precise estimations of the entropy of the source are not possible due to finite sample effects. Compression algorithms also indicate that the redundancy is in the order of 1%. These results confirm the idea that protein sequences can be regarded as slightly edited random strings. We discuss secondary structure and low-complexity regions as causes of the redundancy observed. The findings are related to numerical and biochemical experiments with random polypeptides. Copyright 2000 Academic Press.
------------------------Random, arbitrary sequences of amino acids can also change via random mutation and selection to take on better function. In one case, a random sequence was inserted into a viral genome. Just a small tidbit from the abstract:Can an arbitrary sequence evolve towards acquiring a biological function?"Hayashi Y, Sakata H, Makino Y, Urabe I, Yomo T.Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, 565-0871, Suita City, Osaka, Japan." The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein."The change in sequence was in the D2 domain of the g3p protein. Through mutation and selection there was a 240-fold and a 37-fold increase after the sequence was mutated and clones were selected.To conclude, I have shown that through information theory protein sequences are slightly altered random strings. I have also shown that mutation can increase fitness.My question to you is this, what is stopping the process of random mutation and natural selection from changing amino acid sequences in a way that confers increased fitness? If this process were to continue for long periods of time, by what criteria could you identify genes that were duplicated and left to random mutation over very long time periods (lets say 100 million years)?I am sorry if you feel overwhelmed, but this is the actual state of science. The evidence for the mechanism of improved fitness via random mutation and selection is quite staggering. The above is just the very tip of the iceberg.

Preface: If you are not that familiar with science or science terminology, just read the last couple sentences of each abstract. They usually contain the conclusions of the study. Even us scientists get a little confused with the terminology at times, but the conclusions are usually straightforward.

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A 300 amino acid sequence has 20^300 different combinations. My understanding is that a large number of those sequences will not code for a protein useful to the organism.

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Maybe not in the present, but possibly in the future. Also, it is possible that those proteins were used in the past. Recently, a group of scientists looked through the human genome and found 8,000 pseudogenes. These are genes that were previously functional but are now "broken", that is they are no longer expressed or the protein is mutated so that it no longer works. The number of functional genes in the human genome has been estimated at 30,000. This means that for every 4 functional genes there is 1 non-functional gene that hasn't mutated to the point that it is no longer recognizable. This is what we would expect from an evolutionary process, but not really what we would expect if the human race were 6,000 years old. I really can't see how humans could lose about 20% of their functional genes and still be able to function. We can talk about pseudogenes in another thread if you would like, I am merely using them as an example of protein sequences that are not needed but still had a function. Here is the abstract, I have a feeling that others might be interested in this one too:

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Well I don't think natural selection is going to come into play until a useful sequence is reached. Until then you have to rely on random mutation just coming across a useful sequence by chance.

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That is precisely right. This is exactly the mechanism that causes evolution. Natural selection can only work with what is expressed, not with what is not expressed. However, once a new protein is expressed then natural selection decides the fate of the gene, it decides whether the new gene will spread out into the population because it confers better fitness or if it will be passed to fewer and fewer offspring because it confers less fitness. Neutral mutations, those that don't have an effect on fitness, will not be weeded out by natural selection either. These mutations will usually be spread into the population in a random fashion.

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Natural selection is perfectly able to improve a protein sequence, or preserve a protein sequence, but it is unable to guide a protein sequence for one function to a protein sequence for an entirely different function.

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Why? What evidence is there that backs this up? In my previous post (message 5) I pasted an abstract that argues against this. In this abstract an arbitrary, random sequence was mutated so that it took on a new function, improving infectivity. Also, mutations can cause enzymes to bind to different substrates. Here is one example:

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Then again it could happen by chance via lots of mutations building up and chancing upon a new sequence (but if that was the case wouldn't it be more probable that the gene was damaged eventually?). I just wonder if anyone has done the maths on this or if we simply don't have the numbers to do the maths yet

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It would take a lot of changes and creation of new genes. That means that the diversity in organisms that we see today are the result of numerous changes in DNA, at least according to the theory of evolution. As you stated above, natural selection can preserve functionality in proteins, so I would argue that deleterious mutations would be selected against and the non-mutated alleles would be selected for. You may or not agree with me, but I think the mechanism (mutation and selection) can explain why there are so many different and wonderful species here on earth. However, we may have to agree to disagree, but at least you are trying to learn about the science before you discard it. This is the intellectually honest thing to do and you should be commended for it.To the best of my knowledge, no one is really working on the function of randomly generated proteins. This would be a tough task. Each protein would have to be screened against thousands, perhaps millions, of different substrates in order to deduce its activity or binding capacity. I remember reading a paper about the success of rational mutations having less success than random mutations in creating new functionality. I tried to find it, but it is hiding from me right now. In this paper, scientists had better luck at changing function or deleting function by randomly mutating the gene. The loser was rational mutation, where they tried to deduce the best mutations to get the wanted effect by analyzing the structure of the protein. Anyway, I hope these posts are making things clearer. If not, let me know.

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It is a scientific fact that information can only arise from information and ultimately from a teleonomic (intelligent) source. No where has matter ever been observed to give rise to information.

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It is not a scientific fact. See Percy's post above. Random number generators can create information.Secondly, could you give me an example of what new information at the genetic level would look like? If you don't know what it would look like you can't say it doesn't happen.But, just for a scientific example:Nucleic Acids Res. 2000 Jul 15;28(14):2794-9.Evolution of biological information.Schneider TD.National Cancer Institute, Frederick Cancer Research and Development Center, Laboratory of Experimental and Computational Biology, PO Box B, Frederick, MD 21702-1201, USA. toms@ncifcrf.govHow do genetic systems gain information by evolutionary processes? Answering this question precisely requires a robust, quantitative measure of information. Fortunately, 50 years ago Claude Shannon defined information as a decrease in the uncertainty of a receiver. For molecular systems, uncertainty is closely related to entropy and hence has clear connections to the Second Law of Thermodynamics. These aspects of information theory have allowed the development of a straightforward and practical method of measuring information in genetic control systems. Here this method is used to observe information gain in the binding sites for an artificial 'protein' in a computer simulation of evolution. The simulation begins with zero information and, as in naturally occurring genetic systems, the information measured in the fully evolved binding sites is close to that needed to locate the sites in the genome. The transition is rapid, demonstrating that information gain can occur by punctuated equilibrium.There, evolutionary processes can increase information. If you have a scientific data that refutes this, please post it. If not, then it would seem that it is your own bias that keeps you from seeing the truth.

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Dr. Lee Spetner (biochemist) said that all point mutations studied on the molecular level tend to REDUCE the amount of information. Not increase it.

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Tend to? How about we say point mutations can lower information, but can also increase information. If you want, I can post examples. Of course, I am expecting a hand wave soon.I am sure that you are familiar with the "nylon bug", the flavobacterium that GAINED an enzymatic function due to a FRAMESHIFT MUTATION. How is this not an information gain. If this is not an information gain, give me a concrete hypothetical example of a positive information gain at the DNA level. Not at the phenotype level, but at the genotype level. Show me how adding, subtracting, or changing nucleotides will never increase the information of DNA.[This message has been edited by Loudmouth, 02-10-2004]

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Biologically speaking that is not evolution. If you start with a mouse and you finish wth a mouse, that's not evolution, that's just mice.

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If you start with a mammal, you finish with a mammal.
If you start with a chordate, you finish with a chordate.
If you start with a eukaryote, you finish with a eukaryote.At one point do you draw the line. Also, how would you classify fossils that are intermediate between reptiles and mammals?This is important. Information increases are incremental, not wholesale insertions of new code. You have to show how incremental changes in the genome will not accumulate to such a piont that the new species will not differ greatly from the parent stock. You have yet to show how accumulation is impossible.[This message has been edited by Loudmouth, 02-12-2004]

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I have not seen any fossils that are intermediate between reptiles and mammals. Perhaps you could suggest a few?

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Actually, I found this site which lays out how the progression from reptiles to mammals was a slow process with intermediate steps. For example:

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Unfortunately for Gish, however, many of these mammalian characteristics do indeed leave indications in the fossil record. Cross sections of therapsid bones reveal a series of small holes called Haversian canals, which are typical of fast-growing, warm-blooded animals (and which are absent in cold-blooded reptiles), indicating that the therapsids developed a progressively more mammalian warm-blooded metabolism as time went on. And as the skull and jaws were becoming progressively more and more mammalian, the rest of the body structure was following suit . . .

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So as you can see, there was an accumulation over time of mammalian characteristics. This is something that you seem to be arguing about. If reptiles and mammals were separate creations, why do we find creatures that are intermediate between the two? Easy. It is called evolution.You can also go the the thread Behe's Irreducible Complexity Is Refuted which shows the transition between multiple jawbones and one middle ear bone in reptiles to one jawbone and multiple middle ear bones in mammals. Again, this happens slowly, not in one fell swoop.

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Of course, the explanation alternative to evolution is creation, where random mutation is replaced by genetic engineering by supernatural beings. Now that we have at least the possibility that this explanation can be manipulated by prayer, we might have a means of deciding whether the observed "random mutations" were indeed random and not genetically engineered by some supernatural being.

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When cloning new genes into bacteria you will often get point mutations. This is due to mistakes made by the DNA polymerase in the PCR (polymerase chain reaction, just in case). The interesting part is that certain DNA polymerases actually have a higher fidelity (fewer mistakes) than other DNA polymerases. If mutations were caused by supernatural geneticists, this phenomenon would not be apparent. Instead, fidelity would not be a characteristic of specific DNA polymerases. Sorry, from every indication, point mutations are the result random mistakes, perhaps related to the binding specificity of the polymerase to the correct base. The best analogy I can think of is this: if a deck is shuffled correctly, the distribution of "first cards off the deck" should be random over an infinite amount of tries. If the deck were stacked to help out the reciever of the first card, the overall distributions would tend to show this. We don't see "deck stacking" in mutations.