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Author
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Topic: The GUToB
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Alix Nenuphar
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Member # 686
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posted 22. April 2003 10:13
Peter:
I remain puzzled by your defintion of non-random mutation: are you referring to mutations occuring at preferential points in the genome (which is, I believe the point of Dr. Corpale's work) or mutations which appear to have some causal connection to the environment of the phenotype? Dr. Corpale has indicated that her work is entirely consonant with the NDT, since the NDT only requires that variation (mutational or otherwise) occur randomly with regard to environmental 'appropriateness'.
Could you expand on why you believe that Dr. Corpale's work suggests the abandonment of the NDT? And a clearer defintion of non-random mutation would also be appreciated.
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Pim van Meurs
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posted 22. April 2003 12:04
It may be helpful to understand how Caporale uses the term non-random and compare it to the non-randomness definition in Darwinism which refers to its relationship to the environment. Non-randomness as Alix points out may have different meanings and one has to be careful not to confuse them.
Lynn Caporale: "The adjective frequently applied to the process of "mutation" is "random". However the probability of genetic change is not identical for every nucleotide in a genome. DNA sequence affects DNA structure (Rich, 1982), the fidelity of DNA polymerase (Roberts et al, 1993), and mismatch repair processes (Gläsner et al 1995). The copying of RNA retrotransposons exhibits decreased and non-random fidelity patterns (Gabriel et al, 1996). Also at the RNA level, sequence-dependent genetic variation results from induction of enzymes that edit RNA (Simpson and Maslov, 1994)."
Source
As far as Actinin is concerned, what exactly is your argument? Certainly redundancy/degeneracy is hardly impossible to understand from a Darwinian perspective in fact some have argued that it is almost an inevitable consequence.
As was shown to you Actinin-3 does seem to have some positive function after all. What North showed is how a common mutation can result in Actinin-3 deficiency but how does this support your argument, in fact, what is your argument here?
As far as common descent is concerned, genes may complicate matters but as Caporale has pointed out to you phylogeny can deal with such occurrences. In fact your suggestion that genetic and species discrepancies are somehow disproving NDT seem to be in conflict with your present realization that there may be many mechanisms which could confuse the picture when not carefully examined.
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peter borger
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posted 22. April 2003 22:36
To Alix,
Definitions Non-random mutations:
Non-random Mutations (NRM)
There are two types. The first is often referred to as hot-spots, regions of the genome where mutational change is more common than usual, possibly related to DNA structure. The second is due to genetic mechanisms which serve as a causative force behind mutation.
Non-Random Mutations type 1 (NRM1)
This type of NRM introduces mutations on the same positions and the position where they are introduced depends on the DNA regions where it is part of. NRM1 are also known as ‘positional NRM’.
NRM1 has been described for T4 virus (the mechanism = imperfect hairpin formation). NRM1 is likely to be present in the ZFY region and in mitochondrial DNA.
Implications: NRM1 will line up and give the illusion of common descent in phylogenetic analysis. Since phylogeneticists cannot exclude NRM1, this type of mutations question the evolutionary conclusions that the alignment of genes and shared mutations is proof for common descent?
Non-Random Mutations type 2 (NRM2).
The second type of NRM is mediated by protein and/or RNA driven mechanism that translocate preexisting DNA elements, or vary nucleotides in genes in a similar fashion as observed for immunoglobulins. NRM2 also plays a pivotal role in parasite-host interactions, and are likely to be abundant in other interactions between organisms where ‘evolutionary armsrace’ is ongoing. They have been demonstrated in the 1G5 gene in Drosophila, and in cone snail toxin genes (see Caporale's DitG p27-34).
Implications: NMR2 may give alignment of mutations (‘shared mutations’) in related genomes with the same an/or similar DNA sequences.
It could also implicate that variation is limited and preexistent.
Semi-Random Mutation (SRM)
Semi-random positional mutations are a special form of NRM. SRM are random with respect to nucleotide, but non-random with respect to position (=when mutations occur in the region they are always introduced at the same spot= hotpots).
With respect to Caporale's ideas. As far as I am aware Caporale has NOT indicated that her ideas are entirely consonant with NDT. She has indicated that it is consonant with Darwin. And Darwin assumes one or a few original organic beings (cells) (last page of The Origin).
In her book caporale asks: "The question I would like to raise here [...] is whether mutation always is completely random with respect to its effect on the organism" (DitG, p42)
And than she answers it: "However, I have come to the conclusion that using our current knowledge to expand on Darwin's insights does not require that all mutations be random with respect to their potential effects on biological functions" (DitG, p42)
In my opinion this is opposite of what the NDT-ers had in mind. Of course you can always assume that the mechanisms that induce this variation evolved through a Darwinian mechanism (but that gives a lot of additional problems, since now you have to explain unique genes involved in recombinational mechanism).
I expect that wherever 'evolutionary armsraces' are going on such preexisting mechanism are involved.
Whether or not the mutations have a causal connection to the environment remains to be seen. It has already been demonstrated that mutations in mtDNA are usually found on the same spot and that the frequency is enhanced in reponse to increased levels of radiation in the environment. As a result they line up independently of common descent. I also mentioned that something similar happens in the extended Cairn experiments: a redundant alternative DNA polymerase is induces as a response to stress. Next, the alternative polymerase induces mutations seemingly random, but Rosenberg already noticed that there are "hot" and "cold" spots for these mutations. Apparently these muations also move away from being random. It is definitely not what the NDTers had in mind when they referred to randomness of mutations.
Let me also reiterate that if the mechanisms to induce variation are already preexisting in the genome what is it that Darwin/Wallace observed then? A genetic mechanism that induces variation?.
Last but not least. I have abandoned the idea of randomness of variation inducing mutations when I encountered the peculiar alignment in Drosophila's 1g5 gene.
For sequences go here:
http://www.evcforum.net/DataDropsite/MutationTable.jpg
In brief:
A careful look at the 1g5 genes in subpopulations reveals a couple of intriguing phenomena.
Firstly, although introns vary considerably between the species (13 out of 61 nucleotides are different: 21%), introns within subpopulations of D. melanogaster show nearly no variation (1 out of 61 nucleotides vary in only 3 out of 13 subpopulations: 1.6%). Similarly, introns in the 1G5 gene found in the subpopulations of D. simulans do not demonstrate variation at all. This is a very peculiar, since it is expected that the highest incidence of mutations is within the intron regions of a gene. It is assumed that intron regions are not subject to selection, and are able to mutate at random. This is not only expected between species, but also within subpopulations of one species. Yet, we do not see variation within the introns of subpopulations! In addition, have a close look at the positions of the mutations in the introns between the species. The intron exhibits 13 mutations; 10 out of 13 are immediately adjacent to each other (numbers 153-162). The chance that 10 mutations occur at random within an intron of 61 units equals 1.4 x 10-18. In contrast, the chance that a cluster of 10 adjacent mutations occur in the intron equals 2.2 x 10-14. Therefore, it is reasonable to assume that the cluster of mutations observed in the introns did not arise by a random mechanism.
(By the way, if introns have functions --and for sure they have regulatory-- this comparison is not allowed, and all such experimental work carried out on neutral theory is invalid)
Secondly, the 1G5 genes in subpopulations of D. melanogaster, as far apart as Australia, Russia or Canada are COMPLETELY identical. It either suggests a very high level of stability of the DNA sequences within species or non-random mutations type 2 (NRM2).
Of course, one can speculate that these identical populations are derived from a common founder population after an ice age, or so. But, why would an Australian and not a Japanese or Mexican population of D. melanogaster - which would make much more sense - take over the empty niches in Russia and Canada? Besides, it still would not explain the invariable fixed intron in the 1G5 gene of D. simulans, neither the cluster of 10 adjacent mutations in the introns of both species.
Thirdly, a careful comparison of exon 2 of the 1G5 gene of both Drosophila species uncovers that the genes change with distinctly different rates. Subpopulations of D. melanogaster demonstrate an average of nearly 3 mutations of 803 possible locations (0.37%), whereas subpopulations of D. simulans exhibit and average of 14 mutations (1.7%). Moreover, D. simulans, but not D. melanogaster, demonstrates indel mutations in the 1G5 gene.
Clearly, the genes change at different rates and suggest that the genes have distinct functions or respond differentially to the environment (a parasite?) in either organism. The product of 1G5 gene is of unknown function, but it may be involved in xenobiotic defence mechanisms and may therefore require and direct variation to this DNA element.
Since selection on this region can be excluded (according to the authors the whole region is in accord with Nutral evolution), I propose that an active --protein and/or RNA mediated-- mechanism is involved that induces the variation in the 1G5 gene.
In summary, a close look at the 1G5 gene in Drosophila demonstrates that shared mutations can be introduced irrespective of common descent. To be specific, the mutations introduced in the subpopulations found in Italy, Peru and USA III are non-random with respect to position and nucleotide, i.e. same spot, same nucleotide. If the study was carried out in only these three subpopulations the evolutionary conclusion would have been that these three populations are derived from the same ancestor. However, since there are 10 additional subpopulation for comparison, direct common ancestry is highly doubtful.
Similar results are found for mutations in subpopulations of Australia III and USA I, and for Japan and Peru. These mutations are non-random with respect to where they are introduced and with respect to nucleotide. The Ig5 gene in D. simulans could demonstrate similar things but only three subpopuplations are shown. Here, even indel-mutations may be non-randomly introduced as can be observed for position 605 and probably also for position 835. And that is similar to the indel-mutations found by Lynn Ripley in T4, but probably undelies a distinct mechanism (Ripleys data are NRM1, while this is likely NRM2).
best wishes,
PB
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peter borger
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posted 22. April 2003 22:56
To Pim,
My point is neutral selection. What is it? To explain the redundancies one has to introduce neutral selection. I don't know what it is.
Best wishes,
PB
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Pim van Meurs
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posted 22. April 2003 23:37
Hi Peter,
As I expected you seemed to be confusing non random with respect to the environment with non random with respect to location, variability in time etc.
Nothing new here really although the extent of some of the recent findings are quite exciting since they help understand why Darwinian evolution works even better than Darwin may have envisioned himself.
Your conclusion that alignment of genes are the only proof of common descent seems to limit the strength of the evidence.
So far I see no reason why (neo)-darwinism should be rejected let alone that it has been falsified but perhaps I misunderstand your points?
Hot spots, cold spots are all very interesting but once again do not have much relevance to the randomness as it applies to (neo) Darwinian evolution.
Neutral evolution is but one explanation of degeneracy as observed, others include duplication.
You ask me what is neutral selection? Neutrality refers to the impact of the mutation on the phenotype. There are some excellent papers on RNA and neutral evolution. Neutral networks seem to span most of genotype space and are characterized by few common and many uncommon structures. What was found that most of the common structures are 'closely' located to eachother. There are some excellent papers on these topics
"Neutral evolution of mutational robustness" by Erik van Nimwegen et al in Proc. Natl Acad Sci, vol96, 9716-9720, 1999.
Walter Fontana from the Santa Fe Institute has done some excellent work on mutational robustness, evolvability etc.
Source
quote:
How does robustness to mutation arise through evolution? The simplest naturally occurring object capable of evolution is a single polymer molecule, known as RNA. An important fact about RNA folding is that many sequences do not change their shape when certain positions are mutated. Fontana and colleagues discovered (computationally) that sequences with the same shape are organized into mutationally connected networks called ``neutral networks''. An evolving population can drift on such a neutral network until a more advantageous shape comes within mutational reach. This enables evolutionary change to occur that otherwise would have been impossible. In this way neutrality is seen to be both a buffer against change and an enabler of change.
But as and others have pointed out it is not necessarily redundancy as much as degeneracy which seems to be prevalent in biological systems.
More later on this.
It's later
"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 onditions.
In engineering, redundancy refers to duplication of elements within electric or echanical omponents to provide additional power for rotection from failure or the epetition of messages sending to decrease transmission error. Despite the commonness of redundancy in ngineering, true redundancy in biological system is rarely seen due to the rareness of the presence of identical elements.
On the contrast, examples of degeneracy exist in all fields and all levels of biology, which were discounted as redundancy (Figure 1). In immmunology, different antibodies can bind to the same antigen. In neurobiology, a large number of different brain structures can influence the same motor output and a constrained set of signaling
events can be brought about by a large number of different combinations of stimuli. 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. In the
level concerning the interaction of an individual with other individuals and the environment, enormous kinds of diets are equivalent; although no two “equivalent” neurons taken form two individuals have exactly the same morphology, the two individuals generally behave the same; there are a large number different ways to transmit messages among individuals. A list of degeneracy at different levels of biological organization is shown in Figure 1.
"Measures of degeneracy and redundancy in biological networks." By Tononi et al Proc Natl Acad Sci U S A 1999 Mar 16;96(6):3257-62
Degeneracy and complexity in biological systems
Gerald M. Edelman* and Joseph A. Gally
quote:
The contrast between degeneracy and redundancy at the structural level is sharpened by comparing design and selection in engineering and evolution, respectively. In engineering systems,
logic prevails, and, for fail-safe operation, redundancy is built into design. This is not the case for biological systems. Indeed, not the least of Darwin’s achievements was to lay the
argument by design to rest. But, for obvious economic reasons, design is by far the major component of most technical efforts in modern society. In general, an engineer assumes that interacting components should be as simple as possible, that there are no ‘‘unnecessary’’ or unplanned interactions, that there is an explicit assignment of function or causal efficacy to each part of working mechanism, and that error correction is met by feedback, modeling, or other paradigms of control theory.
Protection can be afforded by planned redundancy, but adventitious compensation for error is neither expected nor usual. Irrelevancy is avoided from the outset. By contrast, in evolutionary systems, where there is no design,
the term ‘‘irrelevant’’ has no a priori meaning. It is possible for any change in a part to contribute to overall function, mutations can prompt compensation, stochastic interactions with the environment can lead to strong selection, often there is no fixed assignment of exclusive responsibility for a given function, and, unlike the engineering case, interactions become increasingly complex. A theoretical analysis (1) suggests that this increase in complexity results not only from selection in rich environments
(which include other species) but also from the prevalence of degeneracy.
They continue to argue that "degeneracy is a prerequisite of natural selection". Quite an interesting paper.
As far as randomness is concerned, Shapiro for instance notices that "The foregoing discussion and an extensiveliterature that cannot be cited here make it clear that MGEs and other natural genetic engineering functions have the capacity to reorganize genomes in just the ways needed to reformat modular genome system architectures. This point is increasingly recognized (e.g. 21,22). However, the degree to which these genome reorganization activities are not random is poorly appreciated. Non-randomness is evident at three levels: mechanism, timing, and sites of action. "
Source
None of these examples are non-random wrt their effect to the organism in the specific environment. That is mutations do not tend to be mostly beneficial.
Talkorigins quotes from Futuyma:
quote:
"The major tenets of the evolutionary synthesis, then, were that populations contain genetic variation that arises by random (ie. not adaptively directed) mutation and recombination; that populations evolve by changes in gene frequency brought about by random genetic drift, gene flow, and especially natural selection; that most adaptive genetic variants have individually slight phenotypic effects so that phenotypic changes are gradual (although some alleles with discrete effects may be advantageous, as in certain color polymorphisms); that diversification comes about by speciation, which normally entails the gradual evolution of reproductive isolation among populations; and that these processes, continued for sufficiently long, give rise to changes of such great magnitude as to warrant the designation of higher taxonomic levels (genera, families, and so forth)."
- Futuyma, D.J. in Evolutionary Biology, Sinauer Associates, 1986; p.12
[ 23. April 2003, 00:00: Message edited by: Pim van Meurs ]
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Pim van Meurs
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posted 23. April 2003 00:03
Another issue. You stated in your introductory posting that
quote:
These redundancies at the level of the genome are the death blow of Darwinism. Why? No association with gene duplication (Winzeler et al, Science 1999, 285:901) and a similar mutation rate as essential genes (Tautz D, TiG 2000, 16:475).
Genetic redundancies are encountered with a lot of disbelief in the orthodox evolutionary community (Nature 2002, 415:8-9). Evolution of robustness?
Could you please provide us with some quotes from these papers which support your claims? I have not had the time to study them in depth but a cursory reading does not seem to support some of your claims here so I would appreciate any help here.
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peter borger
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posted 23. April 2003 01:09
Hi Pim,
I do not confuse non random with respect to the environment with non random with respect to location, variability in time etc. I gave the definitions in my previous mail, and they do not include the environment.
Also I have the feeling that the discovery of preexisting mechanisms that induce the variation and the implications they have for what Darwin observed are not conceived properly.
Although I agree that the recent findings are very exciting it implicates that it is these mechansms that Darwin extrapolated his evolutionary ideas from.
However, since these mechanism are preexisting and specified by the genome one cannot arrive at the conclusion of microbe to man evolution (and certainly not by a random mechanism) since it implicates that ALL information was present from the beginning. Present in the original 'one or few' (or maybe even more) organic beings.
Furthermore, alignment of shared mutation in DNA elements cannot longer be taken as an argument advocating common descent since the mutations line up due to a preexisting mechanism in the genome. For me the alignment was the only convincing argument of Neodarwinian theory. But due to the recently discovered NRM (definitions see in my previous mail) this arguments becomes invalid. It is more likely that multipurpose genomes (MPG) have been designed and what we see now is the decay of these MPGs and since it seems to be subject to molecular mechanisms we see a line up of mutations that are taken as evidence for common descent. I think all we can say is that they are evidence of common origin. But we knew that already.
You say that 'Neutral evolution is but one explanation of degeneracy as observed, others include duplication.' However, one of the observations doen on a Saccharomyces genome wide study (Winzeler et al) demonstrated that there is NO association between redundancies and gene duplications. In Arabidopsis an incredible amount of 98% of the 200 or so examined genes could be inactivated without affecting the phenotype. And also VERY important is that essential genes do not evolve more rapidly than redundant genes. (refs in previous mails). An increased rate of change would be expected in redundant genes since the genes appear to be present in the genome without selective constraint, and thus can undergo more mutations. However, if molecular mechanisms underly the duplications and mutations than such peculiar data can easily be understood.
In fact is was expected that duplication and redundancies are the source for evolutionary novelties. Apparently they are not, but simply contribute to robustness of the organism. Robustness is equivalent to unevolvability, so I see a little evolutionary paradox here. All observations related to biological redundancies (think about the newborn's swimreflex in conjunction with gag reflex) are very peculiar in my eyes and certainly not expected (or explained) from the current theory. Unless one assumes that the information was preexisting in the one or few original Darwinian organic beings. I see no other solution.
I noticed that you had no further comments on the Ig5 gene. It seems to me that an external stimulus is involved that induces a mechanism that mutates this gene. Probably in response to a parasite (=environment).
I will read the papers you provided references for.
Best wishes,
PB
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peter borger
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posted 23. April 2003 01:46
Some quotes:
From Winzeler's paper: "A computational analyis indicated that 8.5% of the identified non essiential ORFs in the yeast genome have a closely related homolog elsewhere in the genome, whereas only four (1%) of the essential genes encoded proteins that were homologous to another predicted protein in the genome. The redundancy may be why more genes in the yeast genome are not essential"
Meaning that over 91% of the redundant genes in Saccharomyces can not be explained by gene duplication.
Tautz's paper confirms this view: "In any case both studies [including Winzeler's study, pb] agree that gene duplications alone do not explain why some genes have no apparent phenotype when knocked out."
Also from Tautz's paper: "...essential genes that are lethal when knocked out, do not necessarily evolve more slowly."
Mario Cappecchi about non-phenotype knockouts in Nature: "I don’t believe that there is a single mouse that does not have a phenotype".
PB
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Pim van Meurs
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posted 23. April 2003 02:17
Dear Peter
You state that "However, since these mechanism are preexisting and specified by the genome one cannot arrive at the conclusion of microbe to man evolution (and certainly not by a random mechanism) since it implicates that ALL information was present from the beginning. Present in the original 'one or few' (or maybe even more) organic beings."
I fail to see why this should be the case. Caporale seems to believe that these mechanisms could have evolved and indeed I see no reason to believe otherwise so far. The suggestion that all information was present from the beginning is an interesting but hard to support assertion imho.
You also state:
quote:
Furthermore, alignment of shared mutation in DNA elements cannot longer be taken as an argument advocating common descent since the mutations line up due to a preexisting mechanism in the genome
Again I would argue that your claims are yet to be supported by any relevant argument. I suggest you spend some time providing us with perhaps a mathematical model that shows why this is the case. Caporale seems to believe that phylogeny can take care of these issues and of course genetic phylogeny as well as non genetic phylogeny still seems to support eachother quite well. Common descent seems as strong as ever despite your claims.
I fail to see how your quotes from the papers have any relevance to your arguments. You seem to quote snippets without any supporting argument which makes it really hard to understand what you are trying to claim.
Nobody is claiming that gene duplication alone is the explanation. i suggest you spend some time reading some of the references in this area and you will realize this.
Gene duplication is one of the ways of generating but it seems that many other mechanisms may help understand the existance of _degeneracy_ without the need for gene duplication to be the only mechanism. Nor do your claims seem to be supported by the papers you quote. I would like to hear how these papers led you to make the claims in your original posting.
it would be helpful if you were to read some of the papers and understand the relevancy of evolution, degeneracy, redundancy and gene duplication as they are all interlocking issues but hardly exclusive.
Duplications are sources for evolutionary novelties but not the only ones and hardly the most prevalent ones. Nor is redundancy/degeneracy dependent on duplication.
So I still do not understand your arguments. Perhaps a short paragraph to propose your arguments in a coherent manner would help further our discussion.
An example of a questionable claim is
"However, one of the observations doen on a Saccharomyces genome wide study (Winzeler et al) demonstrated that there is NO association between redundancies and gene duplications. In Arabidopsis an incredible amount of 98% of the 200 or so examined genes could be inactivated without affecting the phenotype. "
I fail to understand what you are trying to infer from these data. That there is no association ata all between gene duplication and redundancy? ACTN-3 disproves that, that not all redundancy is caused by gene duplication? Noone would argue this either. So what is your argument?
[ 23. April 2003, 02:21: Message edited by: Pim van Meurs ]
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peter borger
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posted 23. April 2003 02:20
to Rex:
Thanks for your response. Deletion may indeed be able to explain the non existence of the putative duplication to reconcile IL-1beta gene. Presently we cannot check whether this deletion really happened. I have no further comments on that since I use it myself in the GUToB. I will focus later on a gene present in humans and deleted in all primates. That sounds more like a nonrandom phenomenon.
More importantly is the SRC family of kinases. Since Src but not Hck is flanked by a K+ channel, protease inhibitor and "Syndecan 4" on the left and a wnt-1 target, hepatocyte transcription factor, "NIDDM3", and a PLC gamma 1 on the right, Hck wasn't copied from Src or vice versa. As far as I am concerned the only mechanism that could explain a duplication that gives rise to an functional DNA element is through unequal crossing over. As mentioned, RNA derived genes lack the regulatory sequences and will not be expressed, unless they come under control of the regulatory sequences of another gene, and that can be checked in the genome. Otherwise they will become pseudogenes. In fact, a translocation after duplication is required for symmetrybreak. If such mechanisms exist they must be stringently regulated and involve several recombinational proteins and thus are not random. However, I am not aware of this and will look into it in more detail.
best wishes
PB
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Ryan Huxley
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posted 23. April 2003 02:24
I'd like to suggest a few definitions related to redundancy that may help the discussion (there have been various definitions suggested in the past threads - again, I can't quickly track this down, but could try if requested):
Repetitive redundancy: identical copies of something.
Functional redundancy: similar function via slightly different methods or pathways
Systematic redundancy: same end goal is achieved, but through drastically different means.
Degeneracy as noted in a previous post is probably similar to the latter two, but has a negative conotation suggesting that something that is redundant is "falling apart." From a design perspective, this wouldn't be correct. I'll grant that this is personal perspective/bias here on my part.
Also, I'd like to ask a few questions from to the evolutionary audience regarding redundancy while making suggestions as well (some of this may have appeard in my last post). First, both evolution and ID would agree that redundancy promotes survivability. But, if redundant systems remain in the "background" and are not regularly exposed to natural selection, passing them on seems unlikely as Peter suggested (i.e. there's no conserving force by natural selection). This problem would become even further compounded if multiple redundant systems were found (are there any?). Additionally, how can various redundant systems not cause interference with each other? It seems that they must be carefully constructed such that they do not negatively impact the primary system. Again, if there are multiple redundant systems, this "layering" effect becomes more problematic from a Darwinian perspective. Furthermore, energy is spent on constructing and maintaining these redundant systems - this seems to be a waste if they do not constantly provide the needed benefit for survival - is there a way to do a cost-benefit analysis on these? I don't have examples of these things, but wonder if others do and how they respond to these queries. Thanks.
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peter borger
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posted 23. April 2003 03:15
Dear Pim,
One of the examples Darwin descibed in his book clearly demonstrates the character of mutations. Some traits can independently arise since the DNA elements are already present in the genome. This is particlularly evident in what Darwin called analogous variation.
From the Origin (p195):
"Distinct species present analogous variations; and a variety of one species often assumes some of the characters of an allied species, or reverts to some of the characters of an early progenitor. These propositions will be most readily understood by looking to our domestic races. The most distinct breeds of pigeons, in countries most widely apart, present sub-varieties with reversed feathers on the head and feathers on the feet, characters not possessed by the aboriginal rock-pigeon; these then are analogous variations in two or more distinct races."
What Darwin observed here is that the same traits appear in distinct breeds of pigeons and these traits appear INDEPENDENT from each other.
Clearly, the mechanisms that lead to the characteristic of feathers on the feet and reversed feathered on the head are already present, pre-existing in the genome of the pigeon as DNA elements that affect gene programs in a non-random sense. In other words, Darwin's examples demonstrate the multipurpose genome of the pigeon in action. Through a pre-existing mechanism some pigeons get the same arrangement of DNA elements that induce the same characteristics independent from each other, and these traits are selected by the breeders. Darwin called this phenomenon of independent acquisition of the same traits 'analogous variation'. It is a common phenomenon well known to breeders. Darwin can easily find more examples of analogous variation:
"The frequent presence of fourteen or even sixteen tail-feathers in the pouter, may be considered as a variation representing the normal structure of another race, the fantail. I presume that no one will doubt that all such analogous variations are due to the several races of the pigeon having inherited from a common parent the same constitution and tendency to variation, when acted on by similar unknown influences. In the vegetable kingdom we have a case of analogous variation, in the enlarged stems, or roots as commonly called, of the Swedish turnip and Ruta baga, plants which several botanists rank as varieties produced by cultivation from a common parent: if this be not so, the case will then be one of analogous variation in two so-called distinct species; and to these a third may be added, namely, the common turnip. According to the ordinary view of each species having been independently created, we should have to attribute this similarity in the enlarged stems of these three plants, not to the vera causa of community of descent, and a consequent tendency to vary in a like manner, but to three separate yet closely related acts of creation." (p195).
Analogous variation must have its origin in the genome through rearrangement of DNA elements that affect gene expression involved in developmental programs. The underlying molecular mechanism must also be non-random in nature; otherwise Darwin wouldn't have mentioned the arrival of same traits independent from each other.
What we discover is that evolution is nothing but reshuffling of preexisting DNA elements that affect regulation of gene expression, or the sequence of gene expression.
Evidence for NRM:
Furthermore, I claimed that alignment of shared mutation in DNA elements cannot longer be taken as an argument advocating common descent since the mutations line up due to a preexisting mechanism in the genome.
With respect to this claim that NRM give the illuion of common descent I would like to discuss the ZFY region in primates:
see for sequences: http://www2.norwich.edu/spage/zfy1a.htm
The figure demonstrates all variable sites present in the ZFY genes in primates. The rows demonstrate the 10 homologue ZFY sequences of 9 primates and 2 species of chimpanzee. The species are presented at the left hand side and abbreviated to three letter codes (plus number): Hsy (Great Gibbon), Ptr1 and Ptr2 (chimp 1 and 2), Ggo(Gorilla), Ppy (Orangutan), Hag (Black hand Gibbon), Mfu (Japanese Monkey), Cae (green Monkey), Lca (Lemur), and Str (Tamarin).
The first row demonstrates the nucleotides as found in the Great Gibbon. The second row the homologous sequence as found in Chimp #1, the third row as found in Chimp #2, etcetera.
The first block of 10 rows demonstrate the first part of the sequenced stretch of DNA in these species, the second block of 10 rows are the second part of the sequenced stretch of DNA, etcetera. Nucleotides are indicated as the letters A, C, G and T. Nucleotides in species that are shared with Great Gibbon (Hsy) are indicated as dots (...), mutations are shown as letters (A, C, T, G). Hence, sequence homologies are dotted and point mutations can easily be observed.
According to evolutionism the shared mutations are due to a mutation that occurred in a common ancestor and has been passed through into the species, thus being proof of common descent. On the other hand the shared mutations could be non-random mutations that have either been introduced on spots that are more prone to mutations --so called hotspot mutations--, while other shared mutations are due to a protein and/or RNA mediated mechanism.
A thorough look reveals that several spots in the homologues sequences demonstrate shared mutations: mutations on exactly the same spot in the DNA of several distinct organisms. Are these shared mutations due to common descent (as proposed by evolutionists) or due to a common mechanism? Let’s find out.
Firstly, let’s have a look at the first block of 10 rows. It is clear that the C on position 22 (from left) in the Great Gibbon is variable throughout the presented species. In 7/10 species we find a C-->T transitions (C22-->T). It should be noted that this mutation does not proof common descent, since the mutation is occurring randomly throughout the species. For instance, while Lemur, Black-hand Gibbon and chimpanzee 2 have a C in this position, all other species have a T. Thus, no consistent evolutionary pattern is observed and is independent of common descent.
Secondly, we observe G88-->T (first block, left hand side) in 4/10 cases. Also no evolutionary pattern is observed. In other words, these point mutations do not proof common descent at all. Apparently the mutations are non-random mutations. Evolutionists will have to claim that the aberrations exist because they have been introduced several times on the same spot, and therefore it is expected that we do not find a perfect alignment of mutations. However, mutations introduced several times on the same spot also implicate a non-random character of these mutations. Less obvious are the non-random mutational spots on position 49 and position 58 (from left hand side).
The second block of 10 rows demonstrates similar findings. Position C9 and A60 in the Great Gibbon sequences also seem to be non-random mutational hotspots unrelated to evolutionary descent.
Position 89 from left hand side is very illustrative for a semi-random mutation: The non-random position is able to change at random with respect to nucleotide. This position demonstrates thus compelling evidence for the hypothesis of non-random mutations.
Finally, another intriguing phenomenon is that the two chimpanzees in the figure demonstrate distinctly different mutations. Isn't it peculiar that exactly the same mutations are also found in Lemur and Tamarin!
What these studies really demonstrate is that mutations in the ZFY region are NON-RANDOM!
Probably introduced there by an unknown molecular mechanism in response to... Yeah what? The environment? If so, NDT RIP.
This example is a VERY strong argument for common mechanisms involved in the lining up of mutations that give the illusion of common descent.
You also say that you fail to see how your quotes from the papers have any relevance to your arguments. What they supported is that redundancies have NO association with gene duplication and that mutaions rate is not associated with degree of redundancy of a gene. It questions the evolutionary origin of redunant genes (and of genes in general). It is evidence for ID.
And degeneracy is easy understood from a multipurpose genome with an excess of DNA elements to induce variation.
The data demonstrated in the papers back up my claims although the authors did not discuss them in the way I discuss them. Data are only data, the scientists do the interpretation. And the interpretation is usually according a paradigm. My paradigm is the GUToB, not NDT.
best wishes,
PB
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charlie d.
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posted 23. April 2003 08:25
Uhm... I always thought that bona fide, strong mutational hotspots would in fact confuse phylogenetic analysis, not give the false appearance of it. That is, if, due to hotspot effects, many independent lineages would converge on the same sequence (the fixation rate being proportional to the mutation rate), independent on phylogenetic relationship, extensive incongruences would result. The fact that molecular phylogenetic incongruences are, in fact, rather rare, would suggest that mutational hotspots are also rare, or generally weak.
As for the actinins, I am not sure what Peter's argument is [incidentally, Peter, I think you should spend a little more time fleshing out your reasoning and background for it; you seem to assume everyone else is up to speed with you from the start, and your lack of specifics about references and unusual jargon just complicate matters].
So, is your argument that the the high conservation and functional redundancy of human ACTN 2 and 3, despite their ancient origin, is evolutionarily inexplicable, because one of the duplicated, redundant partners would be expected to rapidly degenerate into a pseudogene?
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Pim van Meurs
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posted 23. April 2003 14:46
Peter you state that
quote:
Analogous variation must have its origin in the genome through rearrangement of DNA elements that affect gene expression involved in developmental programs. The underlying molecular mechanism must also be non-random in nature; otherwise Darwin wouldn't have mentioned the arrival of same traits independent from each other.
What we discover is that evolution is nothing but reshuffling of preexisting DNA elements that affect regulation of gene expression, or the sequence of gene expression.
A few comments that may help you fine-tune your arguments. You claim that the analogous variation (sounds a lot like convergence) must be non-random in nature. Could you please elaborate in how you are using the term non-random in this case. I am also somewhat surprised by your claim that evolution is nothing more than the reshuffling of preexisting DNA elements. Is this not what evolution has been all the time, variation in genetic material and selection? Point mutations, gene duplications, frame shifts, horizontal gene transfer, recombination are all mechanisms which contribute to this variation and on the other hand there are mechanisms such as selection which act on the variation present. So my question to you is, what is the relevance of your description of analogous mutations and/or your description of evolution?
As far as my comments on your usage of the term non-random, I am pointing out that you are using the term randomness in a different manner than used in (Neo-)Darwinism where randomness refers to a particular variation and its relationship to its environment.
So IL-1B seems to be out as an example that would disprove Neo-Darwinism, Actinin seems to be on its way out with the findings that there may be an effect on the phenotype after all when ACTN3 is 'knocked out' although I still am curious as to the exact nature of your arguments with respect to ACTN3 and its impact on evolutionary theory.
Source: A common polymorphism in the skeletal muscle gene ACTN3 influences athletic performance.
MacArthur et al.
As far as your primate example you claim that "What these studies really demonstrate is that mutations in the ZFY region are NON-RANDOM".
First of all non-randomness of mutations is wrt to location in the genome and thus no real issue for Neo-Darwinism but I find your argument a bit hard to follow. Are you suggesting that the only factor playing a role in these genomes was point mutations alone? No selection ?
Mark24 on the EvcForum states some of my objections quite well: "You are unable to tell the difference between a non-random mutation & random mutation in extant homologous sequences (retrospectively), because both may be carried to fixation & be evident in extant sequences. In other words, you cannot possibly know how many substitutions occurred at a single site before that particular allele was fixed, it might have been one (random), or 500 (non-random). This is especially true when you don’t know what mutagens individual primates had exposure to, & hot spot locations may have moved"
Your interpretation of these records seems to lack a foundation in statistical analysis. Furthermore you make the following comment which suggests some problems in your understanding of evolutionary theory (which you seem to be refering to as evolutionism for some reason).
"According to evolutionism the shared mutations are due to a mutation that occurred in a common ancestor and has been passed through into the species, thus being proof of common descent."
I assume that you are familiar with the term selection? I would suggest that if you are arguing against the theory of evolution that you at least present its ideas in a correct manner. In this case I would argue that you are are creating a nice strawman that has little relevance or similarity to evolutionary theory.
Finally you claim that "What they supported is that redundancies have NO association with gene duplication and that mutaions rate is not associated with degree of redundancy of a gene. It questions the evolutionary origin of redunant genes (and of genes in general). It is evidence for ID."
You seem to be turning a weak claim, not all redundancies are caused by gene duplication to "there is no association between gene duplication and reduncancies", the latter one does not seem to be supported by the papers you have quoted so far. The same applies to your claims about mutation rates. Finally you fail to show why this questions the evolutionary origins and even more why this should be seen as evidence for ID. You seem to be making some very ad hoc assertions here that seem to be missing a lot of intermediate analyses. Could you help us fill in these gaps between your claims and what has been established so far?
[ 23. April 2003, 17:29: Message edited by: Pim van Meurs ]
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Pim van Meurs
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posted 23. April 2003 15:29
Peter,
You mentioned various papers which I would like to discuss in some more detail:
quote:
These redundancies at the level of the genome are the death blow of Darwinism. Why? No association with gene duplication (Winzeler et al, Science 1999, 285:901) and a similar mutation rate as essential genes (Tautz D, TiG 2000, 16:475).
Genetic redundancies are encountered with a lot of disbelief in the orthodox evolutionary community (Nature 2002, 415:8-9). Evolution of robustness?
Winzeler, E.A., Shoemaker, D.D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J.D., Bussey, H., et al. 1999. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285: 901–906.
Winzeler et al looked at ORFs in yeast and then looked at identified non-essential ORFs by deleting 1 of the 2026 ORFS at a time. This represents somewhat more than 1/3rd of the total number of ORFs in the genome. 17 percent of these ORFs were essential for the viability of the yeast, 40% showed quantitative growth defects.
They then found that 8.5% of the identified non-essential ORFs have a homolog elsewhere. This of course does not address gene duplication per se since the other copy may or may not have become silenced or become involved in another function. So did Winzeler et al show "no association of redundancy with gene duplication"? Their own data do not support such a strong conclusion.
Tautz, "A genetic uncertainty problem" Trends in Genetics 2000 Nov;16(11):475-7
quote:
The existence of genes that, when knocked out, result in no obvious phenotype has puzzled biologists for many years. The phenomenon is often ascribed to redundancy in regulatory networks, caused by duplicated genes. However, a recent systematic analysis of data from the yeast genome projects does not support a link between gene duplications and redundancies. An alternative explanation suggests that genes might also evolve by very weak selection, which would mean that their true function cannot be studied in normal laboratory experiments. This problem is comparable to Heisenberg's uncertainty relationship in physics. It is possible to formulate an analogous relationship for biology, which, at its extreme, predicts that the understanding of the full function of a gene might require experiments on an evolutionary scale, involving the entire effective population size of a given species.
Tautz argument seems to be that "Diethard Tautz has argued, in the context of genetic engineering, that subtle genetic changes that do not result in readily observable effects upon individuals in a species may nonetheless have substantial and possibly devastating impacts upon the species in the long term. He has noted that "...genes or genetic functions that have only a very small effect on the fitness of an individual, but are nonetheless important for long-term fitness within a population," an adequate understanding may require "experiments that involve the whole population of the respective species." 96 This genetic "uncertainty principle" means that nearly the entire population would have to be changed to discover whether deleterious changes have occurred. "
Source
From: "fzr-1 and lin-35/Rb function redundantly
to control cell proliferation in C. elegans
as revealed by a nonbiased synthetic screen"
David S. Fay, Sean Keenan, and Min Han
quote:
This apparent lack of an observable gene function
may be the result of limitations at the level of detection as well as in the methodology used in the case of RNAi analysis. However, it is also likely a consequence of functional overlap conferred by either structurally related proteins or by molecularly distinct but functionally connected pathways. Evidence from yeast suggests that this latter explanation may, in fact, be the more common cause of genetic redundancy (Winzeler et al. 1999; for review, see Tautz 2000; Wagner 2000).
And finally
"Surviving a knockout blow" Nature 415, 8 - 9 (2002);
Perhaps Peter can quote from this article to support his arguments?
Now some papers to address some of Peter's claims
Nature 421, 63 - 66 (2003);
"Role of duplicate genes in genetic robustness against null mutations" ZHENGLONG GU et al
quote:
Deleting a gene in an organism often has little phenotypic effect1-5, owing to two mechanisms of compensation4-10. The first is the existence of duplicate genes: that is, the loss of function in one copy can be compensated by the other copy or copies. The second mechanism of compensation stems from alternative metabolic pathways, regulatory networks, and so on. The relative importance of the two mechanisms has not been investigated except for a limited study, which suggested that the role of duplicate genes in compensation is negligible10. The availability of fitness data for a nearly complete set of single-gene-deletion mutants of the Saccharomyces cerevisiae genome11 has enabled us to carry out a genome-wide evaluation of the role of duplicate genes in genetic robustness against null mutations. Here we show that there is a significantly higher probability of functional compensation for a duplicate gene than for a singleton, a high correlation between the frequency of compensation and the sequence similarity of two duplicates, and a higher probability of a severe fitness effect when the duplicate copy that is more highly expressed is deleted. We estimate that in S. cerevisiae at least a quarter of those gene deletions that have no phenotype are compensated by duplicate genes
No correlation was found between the sequence similarity of duplicate genes and the fitness effect of a null mutation in one of the two duplicates when functional data from the yeast S. cerevisiae was analysed previously10. It was therefore concluded that gene duplications contribute little to the ability of an organism to withstand mutations (genetic robustness), although they may be responsible for a small fraction of weak, null-mutation phenotypes12. Because this conclusion was based on only 45 duplicate genes, however, the issue deserves further investigation. Indeed, this conclusion is not supported by a limited analysis of a third of the genes in the yeast genome1 and is contrary to the general observation of relaxed selective constraints after gene duplication13, 14.
"This observation is contrary to the previous conclusion that there is no correlation between KA and the fitness effect of deleting a duplicate gene, which was based on a much smaller data set"
Furthermore redundancy is not only created by gene duplication but by many other mechanisms
quote:
Gene duplication (14)
Neutral codon usage (25)
—
Polyploidy (28)
Multiple regulatory elements for n genes (29)
Chaperone and heat shock proteins (30, 31)
Checkpoint genes promoting repair (32)
Telomerase induction (34)
Dominance (36, 37)
Autophagy (38, 39)
mRNA surveillance (40, 41)
Bulk transmission (42, 43)
Molecular quality control (46)
tRNA suppressor molecules (47)
Modularity (48)
Multiple organelle copies (49)
Parallel metabolic pathways (6, 50)
Correlated gene expression (29, 51)
DNA error repair (52)
From "Redundancy, antiredundancy, and the robustness of genomes"
David C. Krakauer and Joshua B. Plotkin
A good review article on duplication and redundancy can be found in "SPLITTING PAIRS: THE DIVERGING FATES OF DUPLICATED GENES"
Victoria E. Prince and F. Bryan Pickett Nature Reviews Genetics VOLUME 3, 2002 827-837
As far as your claims about phylogeny based on genes and other data, some excellent examples exist which show common descent. In fact Page has provided some of the very relevant data in this area.
Some examples
Genetic Distances Among Primates
Shows the distance matrix for many species. The paper "Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence." by Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP.
Looks at the genetic data and the fossil evidence
According to the posting on the Calvin reflector
quote:
A highly resolved primate cladogram based on DNA evidence is congruent with extant and fossil osteological evidence. A provisional primate classification based on this cladogram and the time scale provided by fossils and the model
of local molecular clocks has all named taxa represent clades and assigns the same taxonomic rank to those clades of roughly equivalent age.
[ 23. April 2003, 16:12: Message edited by: Pim van Meurs ]
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