Thinking About the Theory of Design
http://www.arn.org/docs/orpages/or152/152main.htm
The three-dimensional structure of a protein is determined by its primary sequence. A change in that primary sequence, from a positively to a negatively charged amino acid, for instance, may affect the protein's ability to fold properly, and hence its function. In a small protein of, say, 100 amino acid residues, there are 20 possible amino acids for each site. Thus, the probability of finding the right amino acid for the first site is 1 in 20. The probability of finding the correct two amino acids, in the first and second positions, is 1 in 20^100, and so on. For the entire protein, the probability would be 1 in 20 to the one hundredth power (or 10^130).
Yet it has long been known, Behe continued, that similar proteins from different species show differences in their primary amino acid sequences, while still folding to "closely similar structures." It is possible, therefore, "for two different but similar amino acid sequences to be structurally and functionally equivalent." Some amino acid changes appear to be tolerated. Is there a limit, however, to what changes are possible? And is there a way of answering that question directly (rather than only comparatively)?
At MIT, in the laboratory of Robert Sauer and his colleagues, just such a direct answer was sought for several viral proteins. Taking the genes for the viral proteins, Sauer's group systematically deleted small pieces (corresponding to the instructions for three amino acids at a time), and inserted altered pieces back into the genes at the sites of the deletions. The altered genes, placed in bacteria, produced altered proteins. Since the bacteria quickly destroy proteins which fail to fold properly, Sauer's group was able to isolate the altered proteins that were not destroyed. By sequencing those altered proteins, the biologists could observe which amino acids, in which positions, would produce a folded, functional protein.
What Sauer's group found, said Behe, was that some sites tolerated a great diversity of possible amino acids (up to 15 out of 20 possibilities). Other sites tolerated much less diversity: only three or four amino acids would still yield a functional protein. Other sites, however, had "an absolute requirement for a particular amino acid" --no substitutions would work:
This means that if, say, a P does not appear at position 78 of a given protein, the protein will not fold regardless of the proximity of the rest of the sequence to the natural protein.
Gathering these experimental results over the whole length of the protein, one can readily calculate the likelihood of finding a folded protein by a random mutational search: about 1 in 10 to the 65th power. The number, Behe noted, is "virtually identical to results obtained earlier by theoretical calculations," a confirmation that "greatly increases our confidence that a correct result has been obtained."
Molecular Machines
As "complex and improbable as folded proteins are," said Behe, "in many biological structures [they] are simply components of larger molecular machines." In these larger structures, each protein component functions only "when all of the components have been assembled."
Behe argued, "Examples of irreducible complexity can be found on virtually every page of a biochemistry textbook." Although the cilium is a striking example, because of its manifestly mechanical aspects, other such systems abound:
Other examples of irreducible complexity [include] aspects of blood clotting, closed circular DNA, electron transport, the bacterial flagellum, telomeres, photosynthesis, transcription regulation -- virtually any biochemical system.
"If one looks at other journals or books," he continued, "the story is the same." Sequence comparisons abound, while models for the actual evolution of complex systems are hard to find.
"It is important to realize," Behe said, in ending his talk, "that we are not inferring design from what we do not know, but from what we do know. We are not inferring design to account for a black box, but to account for an open box." While we may be shocked to find open boxes speaking plainly of design, he said, "we must deal with our shock as best we can and go on."
http://www.arn.org/docs/orpages/or152/152main.htm
The three-dimensional structure of a protein is determined by its primary sequence. A change in that primary sequence, from a positively to a negatively charged amino acid, for instance, may affect the protein's ability to fold properly, and hence its function. In a small protein of, say, 100 amino acid residues, there are 20 possible amino acids for each site. Thus, the probability of finding the right amino acid for the first site is 1 in 20. The probability of finding the correct two amino acids, in the first and second positions, is 1 in 20^100, and so on. For the entire protein, the probability would be 1 in 20 to the one hundredth power (or 10^130).
Yet it has long been known, Behe continued, that similar proteins from different species show differences in their primary amino acid sequences, while still folding to "closely similar structures." It is possible, therefore, "for two different but similar amino acid sequences to be structurally and functionally equivalent." Some amino acid changes appear to be tolerated. Is there a limit, however, to what changes are possible? And is there a way of answering that question directly (rather than only comparatively)?
At MIT, in the laboratory of Robert Sauer and his colleagues, just such a direct answer was sought for several viral proteins. Taking the genes for the viral proteins, Sauer's group systematically deleted small pieces (corresponding to the instructions for three amino acids at a time), and inserted altered pieces back into the genes at the sites of the deletions. The altered genes, placed in bacteria, produced altered proteins. Since the bacteria quickly destroy proteins which fail to fold properly, Sauer's group was able to isolate the altered proteins that were not destroyed. By sequencing those altered proteins, the biologists could observe which amino acids, in which positions, would produce a folded, functional protein.
What Sauer's group found, said Behe, was that some sites tolerated a great diversity of possible amino acids (up to 15 out of 20 possibilities). Other sites tolerated much less diversity: only three or four amino acids would still yield a functional protein. Other sites, however, had "an absolute requirement for a particular amino acid" --no substitutions would work:
This means that if, say, a P does not appear at position 78 of a given protein, the protein will not fold regardless of the proximity of the rest of the sequence to the natural protein.
Gathering these experimental results over the whole length of the protein, one can readily calculate the likelihood of finding a folded protein by a random mutational search: about 1 in 10 to the 65th power. The number, Behe noted, is "virtually identical to results obtained earlier by theoretical calculations," a confirmation that "greatly increases our confidence that a correct result has been obtained."
Molecular Machines
As "complex and improbable as folded proteins are," said Behe, "in many biological structures [they] are simply components of larger molecular machines." In these larger structures, each protein component functions only "when all of the components have been assembled."
Behe argued, "Examples of irreducible complexity can be found on virtually every page of a biochemistry textbook." Although the cilium is a striking example, because of its manifestly mechanical aspects, other such systems abound:
Other examples of irreducible complexity [include] aspects of blood clotting, closed circular DNA, electron transport, the bacterial flagellum, telomeres, photosynthesis, transcription regulation -- virtually any biochemical system.
"If one looks at other journals or books," he continued, "the story is the same." Sequence comparisons abound, while models for the actual evolution of complex systems are hard to find.
"It is important to realize," Behe said, in ending his talk, "that we are not inferring design from what we do not know, but from what we do know. We are not inferring design to account for a black box, but to account for an open box." While we may be shocked to find open boxes speaking plainly of design, he said, "we must deal with our shock as best we can and go on."
