Friday, February 10, 2006
More on Directed Mutagenesis
Our understanding of mutagenesis is showing that mutagenesis is not the haphazard process it was previously thought to be.
Creationists are sometimes falsely accused of having a static view of organisms (and in fact, many lay creationists who have not studied the issue have this view). However, there is no discrepancy between genomic change and creationism. The creationist view is distinctive, however, in that it views multiple categories of change. Cell-directed mutagenesis is characteristically adaptive and beneficial to the cell. Non-directed mutagenesis is almost always damaging to the cells (it can, on occasion, generate some form of benefit, but this is rare, and it is usually outweighed by problems, as in sickle-cell anemia, which prevents malaria.
Anyway, I thought I'd put together a list of articles and ideas supporting directed mutagenesis for those interested. Most of these are investigated in single-celled organisms. Whether or not they are applicable to multicellular organisms has not been as thoroughly examined.
First of all, contingency loci are hypermutable spots of genomes. These spots have been well-known in biology for some time. The interesting things about contingency loci is that these locations are (1) they usually allow a specific, discrete amount of variation, and (2) they are very useful for adaptive purposes, such as antibiotic resistance.
The definitive paper describing contingency loci seems to be Adaptive evolution of highly mutable loci in pathogenic bacteria. I have not read this paper, but a number of papers I have been reading reference this one. From the abstract:
By directing mutation to specific genes, you lessen the problems of error catastrophe by restricting change to specific locations which are built for it.
The paper Environmental regulation of mutation rates at specific sites gives several lines of evidence showing that the rate of changes to these hypermutable loci are specifically affected by environmental conditions which affect the loci. The cell may not know which specific mutation is necessary (that was not determined in the paper), but it does seem to at least know which contingency loci needs to be tampered with.
The paper A Biochemical Mechanism for Nonrandom Mutations and Evolution describes a very interested idea for the mechanism for directed mutations in bacteria. In this review, Wright noted that there are many destabilizing factors in the genome, including proofreading errors during replication, recombination, transcription, and repair. The question is, which of these mechanisms get activated by the cell when the cell is in trouble? The answer is, transcription.
When the DNA is separated into separate strands, it forms stem-loop structures when there are complementary segments which are separaated by 5 to 10 noncomplementary bases. The complementary segments line up, and the noncomplementary bases are subject to numerous types of mutations, such as deamination, deletion, replacment, or complementation.
This seems to be quite an ingenious mechanism that God used to isolate the changeable portions of genes. It seems kind of like a snap-on-tool-like mechanism. Wherever there is a stem-loop, we can substitute various pieces into the DNA to modify it in predictable, specific ways at specific sites.
An interesting quote from the article is this:
The overall gist of the paper is that we can use the secondary structures formed by DNA to predict where mutations are likely to be directed to. In addition, the cell can choose to transcribe certain regions of the genome under stress, in order to activate mutation in those areas to respond to the stressor.
Wright developed an "algorithm for evolution" which looks like this:
Transposons will have to be saved for another time. It's late and I'm tired.
Hopefully I have demonstrated here that genomic change is an active, not a passive mechanism, with respect to adaptive changes. There are spots which are specifically intended for mutation, and these changes are directed by the cell in response to environmental conditions.
This is especially reasonable in a Creationist framework, as it indicates that the cell is "aware" of its own constraints of change, and knows which changes do and do not conform with the cell's overall semantics. It also suggests a method of comparative genomics which examines the differences in secondary structure (and thus hypermutable spots) in different taxa. My guess would be that different baramins would have different hypermutable spots in genes responsible for consumption and other environmental factors, in order to facilitate integration with that baramin's own semantic restrictions.
Creationists are sometimes falsely accused of having a static view of organisms (and in fact, many lay creationists who have not studied the issue have this view). However, there is no discrepancy between genomic change and creationism. The creationist view is distinctive, however, in that it views multiple categories of change. Cell-directed mutagenesis is characteristically adaptive and beneficial to the cell. Non-directed mutagenesis is almost always damaging to the cells (it can, on occasion, generate some form of benefit, but this is rare, and it is usually outweighed by problems, as in sickle-cell anemia, which prevents malaria.
Anyway, I thought I'd put together a list of articles and ideas supporting directed mutagenesis for those interested. Most of these are investigated in single-celled organisms. Whether or not they are applicable to multicellular organisms has not been as thoroughly examined.
Contingency Loci
First of all, contingency loci are hypermutable spots of genomes. These spots have been well-known in biology for some time. The interesting things about contingency loci is that these locations are (1) they usually allow a specific, discrete amount of variation, and (2) they are very useful for adaptive purposes, such as antibiotic resistance.
The definitive paper describing contingency loci seems to be Adaptive evolution of highly mutable loci in pathogenic bacteria. I have not read this paper, but a number of papers I have been reading reference this one. From the abstract:
Bacteria have specific loci that are highly mutable. We argue that the coexistence within bacterial genomes of such 'contingency' genes with high mutation rates, and 'housekeeping' genes with low mutation rates, is the result of adaptive evolution, and facilitates the efficient exploration of phenotypic solutions to unpredictable aspects of the host environment while minimizing deleterious effects on fitness.
By directing mutation to specific genes, you lessen the problems of error catastrophe by restricting change to specific locations which are built for it.
The paper Environmental regulation of mutation rates at specific sites gives several lines of evidence showing that the rate of changes to these hypermutable loci are specifically affected by environmental conditions which affect the loci. The cell may not know which specific mutation is necessary (that was not determined in the paper), but it does seem to at least know which contingency loci needs to be tampered with.
Transcription-directed Evolution
The paper A Biochemical Mechanism for Nonrandom Mutations and Evolution describes a very interested idea for the mechanism for directed mutations in bacteria. In this review, Wright noted that there are many destabilizing factors in the genome, including proofreading errors during replication, recombination, transcription, and repair. The question is, which of these mechanisms get activated by the cell when the cell is in trouble? The answer is, transcription.
When the DNA is separated into separate strands, it forms stem-loop structures when there are complementary segments which are separaated by 5 to 10 noncomplementary bases. The complementary segments line up, and the noncomplementary bases are subject to numerous types of mutations, such as deamination, deletion, replacment, or complementation.
This seems to be quite an ingenious mechanism that God used to isolate the changeable portions of genes. It seems kind of like a snap-on-tool-like mechanism. Wherever there is a stem-loop, we can substitute various pieces into the DNA to modify it in predictable, specific ways at specific sites.
An interesting quote from the article is this:
It is noteworthy that the experiments described above on the effects of artificially induced transcription on mutation rates in growing cells are all examples of specifically directed mutations. However, none of the researchers come to that conclusion or challenge the assumptions and implications inherent in the experiments of Luria and Delbruck, which reinforce neo-Darwinism. This situation may be due to the dominance of current dogma and to the assumption that mechanisms operative during growth cannot also be critical during evolution under conditions of environmental stress.
The overall gist of the paper is that we can use the secondary structures formed by DNA to predict where mutations are likely to be directed to. In addition, the cell can choose to transcribe certain regions of the genome under stress, in order to activate mutation in those areas to respond to the stressor.
Wright developed an "algorithm for evolution" which looks like this:
- Environmental Stress
- Targets Specific Genes for Derepression
- Exposes the Non-transcribed DNA Strand and Drives Supercoiling
- Forms and Stabilizes Secondary Structures
- Creates Unpaired and Mispaired bases
- Causes Hypermutation at Vulnerable sites
- Increases Availability of Variants Most Likely to Survive the Stress
- Selects the Fittest
Transposons
Transposons will have to be saved for another time. It's late and I'm tired.
Conclusion
Hopefully I have demonstrated here that genomic change is an active, not a passive mechanism, with respect to adaptive changes. There are spots which are specifically intended for mutation, and these changes are directed by the cell in response to environmental conditions.
This is especially reasonable in a Creationist framework, as it indicates that the cell is "aware" of its own constraints of change, and knows which changes do and do not conform with the cell's overall semantics. It also suggests a method of comparative genomics which examines the differences in secondary structure (and thus hypermutable spots) in different taxa. My guess would be that different baramins would have different hypermutable spots in genes responsible for consumption and other environmental factors, in order to facilitate integration with that baramin's own semantic restrictions.
Permanent Link posted by crevo @ 9:59 PM 
