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Topic: What comes after detecting design?
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peter borger
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posted 10. July 2003 22:33
Argon,
A non-native english speaker I've looked up 'degenerate' in the The Oxford Dictionary. The definitions are:
1) having LOST the qualities that are normal and desirable or proper to its kind; fallen from former excellence,
2) Biol. having changed to a LOWER level.
So, I proof my point (again). The initial evolutionary idea must have been that 64 codons specified for..........(yeah what?) 64 AA? 63+stop? Other? And ultimately life ended up with a code specifiying only 20 AA+stop. That makes the code degenerate according the Oxford Dictionary meaning. However, the code is NOT degenerate -maybe it is redundant- but considering the additional regulatory codes in protein coding DNA elements it has been designed as the most optimal design to specify 20 AA and 64 possible codons to choose from.
O, I see selection did the optimization. Selection can be easily be falsified at the genomic level so I (and you) should really start to doubt that.
quote:
It has been known for decades that some genes can be regulated by specific codon preferences.
How many decades? 12? 3? Sustain your claims with scientific references, please.
And the neutrality of codon usage remains to be established in the light of tranlational control of mRNA. It should be noted that some intronless genes can be alternatively translated and this is affected by alternative codon age. That tells me that the code may seem neutral but in fact it is not. 'Neutral' mutations disturbs intricate regulatory balances and thus result in suboptimal protein expression patterns. But we can (suboptimally) live with that.
PB
[ 10. July 2003, 22:48: Message edited by: peter borger ]
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peter borger
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posted 11. July 2003 02:28
Hi Pim,
Thanks for the references.
quote:
Hardy D.O., Bender P.K., Kretsinger R.H.;
"Two calmodulin genes are expressed in Arbacia punctulata. An ancient gene duplication is indicated."; J. Mol. Biol. 199:223-227(1988).
I wonder though how the authors distinguish between loss of an ancient CALM gene from a MPG(from 3 to 2) and ancient duplication (from 1 to 2)? Or is it just another assumption?
PB
[ 12. July 2003, 03:32: Message edited by: peter borger ]
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Argon
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posted 11. July 2003 09:47
peter borger writes:
quote:
A non-native english speaker I've looked up 'degenerate' in the The Oxford Dictionary. The definitions are:
1) having LOST the qualities that are normal and desirable or proper to its kind; fallen from former excellence,
2) Biol. having changed to a LOWER level.
So, I proof my point (again).
I think not. None of those definitions are pertinent to the "degeneracy of the triplet code". Try doing a Google search that includes these terms: "degenerate codon dictionary". Or better, try this link to the American Heritage Dictionary: here.
You'll find the following under "degenerate":
"6. Biology Having lost one or more highly developed functions, characteristics, or structures through evolution: a degenerate life form.
7. Genetics Having more than one codon that may code for the same amino acid."
Note that the genetics definition is the relevant one for this conversation. It specifically addresses what it means when one says "The triplet code is degenerate". The use of the term (in English) in this manner is based on an explicit definition in molecular biology: There is nothing further to discuss about it. As I mentioned previously, what you are talking about is not codon "degeneracy" but the neutrality of codon substitution.
Here is another reference from Genes V a common textbook on molecular biology by Benjamin Lewin, founder & former editor of the journal, Cell (pp. 172-173): "The code is summarized in Figure 7.9. A striking feature is its degeneracy: almost every amino acid is represented by several codons."
I will try to dig up references about the effect of codon preferences on gene expression and regulation this weekend. I believe they go back to the mid- to late-1970's.
[ 11. July 2003, 13:15: Message edited by: Argon ]
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Argon
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posted 11. July 2003 11:06
I wrote that gene expression can be regulated by codon preferences at that this data has been available for decades.
peter borger asked:
quote:
How many decades? 12? 3? Sustain your claims with scientific references, please.
Almost three. The early references to translational attenuation are from 1977/1978. Use Medline to search for "Yanofsky C" to pull up relevant papers. In particular, see the 1977 paper "Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination" (w/ F Lee) - PNAS 1977 Oct;74(10):4365-9. What is important here is not the tryptophan codons in the leader portion of the peptide that can "stall" ribosomal translation, but the hairpin loop structures which form immediately downstream and which block the stalled ribosome (& consequently reduce transcription). These loops result from specific base-pair matching and thus depend entirely on the primary nucleotide sequence. Hence, regulation will be sensitive to changes in codon usage in these loop regions.
Similar mechanisms are found in other operons.
The rarity of some tRNAs (i.e. low abundance tRNAs specific for particular codons) is also known to affect expression. A search on Google for "rare codon regulation" turns up a large number of hits (I love Google), which turns up several papers on this subject. One useful, general reference the search returns is from a course guide here, which reviews key papers related to translational regulation.
[ 11. July 2003, 11:08: Message edited by: Argon ]
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peter borger
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posted 12. July 2003 03:28
Hi Argon
Thanks for the references. Still I wonder why the code is referred to as degenerate. There must be an etymological connection between 'loss of quality' and what they thought to observe on the genetic code. Why would evolutionary biologists refer to the code as degenerate? Why not 'redundancy of the code'? Or simply 'genetic code'?
Besides, it's not only the genetic code. There is more to it. As mentioned the code may also specify where and when proteins are transcribed or translated. For instance protein-DNA binding codes. And probably even the histon code may indirectly be affected by third codon positions. In conclusion, coining the term degeneracy of the genetic code is coining from ignorance.
PB
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John Wendt
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posted 12. July 2003 07:24
From Peter Borger: quote:
Still I wonder why the code is referred to as degenerate.
I suspect that the term "degenerate" was applied to the code by someone with a mathematical background (maybe the renegade physicist Francis Crick).
From Wikpedia quote:
In mathematics, a degenerate case is a limiting case in which a class of object changes its nature so as to belong to another, usually simpler, class
In this case the simpler class is a two- or two-and-a-half base codon instead of three. quote:
In conclusion, coining the term degeneracy of the genetic code is coining from ignorance.
Quite possibly the term was first applied before people really understood what was gong on. There's a lot of that in biology. "Pseudogene" comes to mind. It looked like a gene, but it took a while to figure out what it really was. In the meantime the term stuck.
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Pim van Meurs
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posted 12. July 2003 15:44
Peter Borger wonders about the usage of the appropriate term degeneracy when discussing the genetic code.
Some useful references include
Degeneracy, Redundancy & Complexity in Biological Systems & Their Measures by Qing-jun Wang
quote:
A good portion of biological complexity comes from degeneracy. Degeneracy is used to designate different wave function satisfying the same energy state in quantum mechanics. In biology, degeneracy is “the ability of elements that are structurally different to perform the same function”. However, for many years, the concept of degeneracy is lacking and confused with redundancy, which occurs when the same function is performed by identical elements. Unlike redundant elements, degenerate elements can produce different outputs under different conditions.
and
quote:
In a cellular level, genetic code is degenerate with different codons coding for the same amino acid; transcription of a gene is degenerate with different 5’ start site, 3’ termination site, and degenerate transcription machinery; translation is degenerate with alternative splicing; protein folding is degenerate with different primary sequences lead to similar protein structures and functions; enzyme activity is degenerate with different proteins catalyzing the same enzyme reaction; metabolism is degenerate with the existence of multiple parallel anabolic and catabolic pathways. In a multicellular level, many different patterns of muscle contraction yield equivalent outcome; neural connectivity is highly degenerate in that although no two neural cells within an individual are identical.
Hope this helps, the use of the term degeneracy seems to be related to its usage in mathematics and physics. Nothing really to do with the definitions proposed by Peter.
[ 12. July 2003, 16:23: Message edited by: Pim van Meurs ]
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Argon
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posted 12. July 2003 17:41
If one is interested in the origin of the term "degeneracy" and the genetic code, it might be worth going back to the papers from the 1960's when the code was first "deciphered".
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peter borger
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posted 12. July 2003 22:35
considering the etymology of 'degeneracy' it implies a preconceived idea about the code. I wonder what this idea is. Probably it has something to do with the evolutionary paradigm. Anybody to explain?
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peter borger
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posted 12. July 2003 22:39
John:
quote:
"Pseudogene" comes to mind. It looked like a gene, but it took a while to figure out what it really was.
What is it?
PB
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Pim van Meurs
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posted 12. July 2003 22:49
Peter: considering the etymology of 'degeneracy' it implies a preconceived idea about the code.
Nope it merely describes the fact that multiple codons can code for the same amino acid. Its usage is not dissimilar from degeneracy as used in mathematics and physics. Did you read my posting?
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peter borger
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posted 12. July 2003 23:30
Rex:
quote:
I find your statement "On the contrary, the mutation-selection hypothesis would rather predict that super-conserved redundant gene families do not exist!" to be in need of some supporting arguments. Would you care to explain?
The calmodulins are a family of sodium binding proteins. Three functional protein-coding copies are present in all known vertebrates and involved in the regulation of intracellular distribution of sodium and crucial for maintaining cellular homeostasis. The calmodulin gene family exists of 3 genes, called CALM1, CALM2 and CALM3. The genes are located on different chromosomes; CALM1 on chromosome number 14, CALM2 on chromosome number 2, and CALM3 on chromosome number 19.
The calmodulin genes are three variable genes due to neutral mutation on silent positions in the genes, and they spawn 5 different messengers (RNA) to produce the calmodulin proteins. Only one invariable calmodulin protein is specified by these genes. Thus, three similar genes located on different chromosomes code for only one invariable protein. The most remarkable, however, is that all known vertebrates, including humans, rats, chicken, frogs, and fish, encode exactly the same non-variable calmodulin proteins. It should also be noted that cell-line knockouts, in which one of the calmodulin genes has been inactivated, demonstrates the cells to be viable with only minor effects on cell proliferation. Apparently, the calmodulins genes demonstrate a high degree of redundancy.
It should be clear that the information of at least one original calmodulin gene must have been present in the common ancestor of vertebrates. It has to be assumed that the complete original gene plus regulatory sequences of that gene were duplicated to give rise to the second calmodulin gene. It must have been some kind of extensive duplication event, because the genes would lack regulatory sequences if they were derived from processed pseudogenes. (Not expressed is not maintained). In contrast to classical pseudogenes, which are usually found in the vicinity of the functional gene from which they are derived by duplication, processed pseudogenes are apparently inserted into DNA at random locations. It should be noted that the CALM genes are not in each others vicinity, but on dictinct chromosomes (for obvious design reasons).
ToE says that an additional duplication of one of the complete calmodulin genes plus regulatory sequences gave rise to the second copy of the calmodulin gene. That makes three of them. Next, the copies plus regulatory sequences have relocated to other chromosomes by excision and reintegration or segmental chromosome duplication where they come under the supervision of cell specific regulatory elements (promoters/enhancers).
Why didn't the protein evolve after duplication? Most likely ToE holds that there has been selection against. But if that is true than you cannot explain the existance of the original (first) copy by a evolutionary mechanism. Does it explain why the proteins did not change in different classes of organisms over time through the random accumulation of mutations in the genes? Even before triplication the genes are free to diverge in different organisms. That's what evolution is about: duplication and divergence. For instance, it is known that non-vertebrate organisms also express calmodulins. Although these proteins are different at several amino acid positions, they exhibit the same function as the vertebrate calmodulins. Therefore, a degree of variability at the amino acid levels would be expected even in the vertebrates. In particular since they can substitue for each others function (they are redundant).
In addition, and this is a general phenomenon for redundant gene families, how do the genes plus their regulatory sequences relocate to other chromosomes and how do the manage to be stable in the genome? Purifying selection on redundant genes? Molecular biology does not provide a mechanism how single genes are excised and reintegrated. If such mechanism were to exist one might expect a tremendous amount of variation in genomic organisation within species. The human genome project would not have been possible, because the observed organisation of genes would only reflect the organisation of the screened individuals! Besides genomes prefer stability.
Furthermore, it is very peculiar why all vertebrates have three functional copies. We know that after the initial duplications of the genes in the common ancestor of all vertebrates, the genes spawned two copies of the calmodulin gene because they are present as pseudogenes. Evolution biologists will speculate that none of the additional duplications adopted another function and became pseudogenes. But why didn’t they disappear over time without leaving a trace through mutational drift as predicted by the theory of evolution. After all we are able to trace back the calmodulin pseudogenes for about 300 million years. According to neutral molecular evolution this is very unlikely since all nucleotides in the genes should have been randomly replaces within 100-300 million years.
ToE does not only fail to provide a reasonable explanation for the existence of the calmodulin gene family, it would rather predict that such conserved redundant gene families do not exist. It would not only predict differences between calmodulin proteins in distinct classes of organisms, but also between the three copies of calmodulin within one species. What we observe, however, are completely conserved proteins. The existence of the conserved calmodulin gene family poses a real challenge to the putative random mechanisms involved in evolution, and it doubts the significance of selection on the maintenance of genes.
IMO multiple copies of the CALM genes were already present in the MPG of ur-vertebrates.
The knockouts will shed further light on this matter would be my guess.
PB
[ 12. July 2003, 23:34: Message edited by: peter borger ]
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Argon
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posted 13. July 2003 11:56
peter borger writes:
quote:
considering the etymology of 'degeneracy' it implies a preconceived idea about the code. I wonder what this idea is. Probably it has something to do with the evolutionary paradigm. Anybody to explain?
I'd suggest reading the original papers by H. Gobind Khorana, Marshall W. Nirenburg, and others of that period (late 1950's, early 1960's). For starters, here is a link to Khorana's 1968 Nobel Lecture on the deciphering of the triplet code (click here). Note that on pages 14-15 of the .pdf (pp. 354-355 of the original publication), Khorana writes: "The code is highly degenerate in a semi-systematic way. Most of the degeneracy pertains to the third letter, where all of four bases may stand for the same amino acid or where two purines may stand for one amino acid and the two pyrimidines may stand for another amino acid." (All typos mine).
Marshall W. Nirenburg's writes in his Nobel Lecture: "The results showed that multiple codons can correspond to the same amino acid: hence the code is highly degenerate." (p. 6 of .pdf, p. 377 of original publication). Later he discusses "rules governing degeneracy" and "degeneracy patterns" but this is all about correspondence to amino acid incorporation. Nirenburg says nothing with regard to evolution in this lecture.
I did not see Nirenburg mention anything about evolution, much less the origin of the genetic code in his lecture. Robert W. Holley, who also shared the 1968 prize with Khorana & Niremburg similarly writes nothing about evolution in his lecture. A link to the Nobel site for the 1968 award in Physiology or Medicine is here.
Peter, when you finish researching the historical origins of the term "degenerate" as applied to the genetic code, would you mind reporting your findings here? Thanks.
[ 14. July 2003, 09:30: Message edited by: Argon ]
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Pim van Meurs
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posted 13. July 2003 14:14
Peter suggests that 'ToE does not only fail to provide a reasonable explanation for the existence of the calmodulin gene family, it would rather predict that such conserved redundant gene families do not exist. '
Could you please explain why the ToE fails to provide a reasonable explanation for the Calmodulin gene family? As I have shown, gene duplication seems to quite well explain this gene family.
I find your claim fascinating but I believe it to be quite erroneous. Could you perhaps explain in more detail how ToE would fail ?
Perhaps Peter's problem can be found in this statement "Even before triplication the genes are free to diverge in different organisms. That's what evolution is about: duplication and divergence.". In fact evolution is not all about duplication nor divergence. Evolution is about variation (which may include duplication) and selection. Under strong selective pressures genes may remain quite well conserved for instance.
For an interesting example where researchers used calmodulin
"Evolutionary relationships of Metazoa within the eukaryotes based on molecular data from Porifera Joachim Schuetze, Anatoli Krasko, Marcio Reis Custodio, Sofia M. Efremova, Isabel M. Mueller and Werner E. G. Mueller" in Proc. R. Soc. Lond. B (1999) 266, 63-73
[ 13. July 2003, 15:14: Message edited by: Pim van Meurs ]
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Ben Kissling
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posted 13. July 2003 16:22
quote:
Unless and until design research provides some chance of actually bearing fruit, it's not a real viable pathway. Once again, I urge ID proponents to spend less time critiquing evolution and exhorting the troops, and to spend their time and effort on designing (!), executing, and publishing actual design-based research. The dearth of such research is a discouraging sign for potential workers.
This is a very good point RBH. As much as the ideas of irreducible complexity, specified complexity, etc. are good ones and worth exploring, they are still negative in the sense that they don't "bear fruit".
Here's an idea. If we are finally able to distinguish designed information that's already here, why don't we start looking for designed information that is no longer here? It is my firm belief that random mutations are almost always "bad" in the sense that information is lost because of them. If random processes cannot create or recreate that information, it is designed and requires an intelligent agent. Is it possible that we are intelligent enough to recreate that information? What I mean is not some off the wall bioengineering "let's make ourselves superheroes" stuff. What I mean is looking at the genetic information we have and trying to find things that have mutated out of biological systems. Mutations like transposition could be reverse engineered to find out what the original designer made. That would be valuable, would it not?
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