Another Protozoan and Front-Loading
by MikeGeneSingled-celled eukaryotic organisms known as Tetrahymena contain many features that make them a good candidate model for front-loading evolution. - Here
Singled-celled eukaryotic organisms known as Tetrahymena contain many features that make them a good candidate model for front-loading evolution. - Here
September 2nd, 2006 at 1:54 am
Mike you quoted Krauze's prediction:
"So, if the first eukaryotes (a large group of organisms, which includes plants, animals, fungi, and several one-celled organisms) were front-loaded for multicellularity, we would expect them to contain genes required for multicellular life."
This is perfectly reasonable.
However, of the gene families in the paper, I didn't see any hint of any the gene families involved in communication between cells of a multicellular organism, such as hormone receptors, cell-cell adhesion proteins, etc. All the families were of genes required for UNIcellular life.
"Because front-loading predicts such deep homology, it makes a practical prediction - as we sequence the genomes of about more and more exotic protozoa, we will uncover cells that will serve as useful models for understanding various human diseases."
I don't follow this. Why wouldn't cells from humans or mice be far better models?
"With Tetrahymena, many of the genes shared by this protozoan and humans (but not shared by humans and fungi) have already been implicated in human diseases."
But would any of those be human diseases involving characteristics of multicellular organisms?
I also don't get your highlighting of kinases, given that the amazing thing about the second-messenger pathways that often include kinases is that complex multicellular organisms have so few of them.
Comment by Smokey — September 2, 2006 @ 1:54 am
September 2nd, 2006 at 8:46 am
More indications of how deeply rooted in biology the RNA World is.
Comment by Art — September 2, 2006 @ 8:46 am
September 2nd, 2006 at 9:53 am
More evidence of genomic regulation as an interdependent process involving nucleic acids and proteins is a more accurate description.
Comment by Bradford — September 2, 2006 @ 9:53 am
September 2nd, 2006 at 12:00 pm
As I mentioned in a previous blog, I simply do not have the time for on-going involvement in this blog for the next few months. So I will restrict myself to a single reply.
Yes, we've seen some of this in the choanoflagellates. It is important to keep in mind that I am not arguing for the reality of front-loading; I am still fleshing out the plausibility of front-loading. As such, your point is one that stimulates questions and potential research. The completed genome of Tetrahymena simply allows us our first good model to begin thinking along these lines (after all, we have very few sequenced single-celled eukaryotes, and even fewer that are free-living).
The paper indicates there were 654 genes shared by Tetrahymena and humans, but not shared with other single-celled organisms. The families the researchers focused on were chosen for closer analysis because their propensity for expansion. I'd be more interested at looking more closely at all 654 genes to determine how closely they are associated with the multicellular state. And I think we can go beyond the detection of things such as hormone receptors, cell-cell adhesion proteins, etc. But that's getting in The Matrix.
I didn't say "better." The point here is that some protozoa may turn out to make surprisingly good models for various human diseases that can help complement the mouse work. And the protzoa would be a lot cheaper and easier to work with.
Now you are starting to see how FLE can guide research. A closer look is needed.
So the evolution of "complex" multicellular organisms may have involved molecular stream-lining. Imagine that.
Tetrahymena has long played a crucial role in helping us appreciate the significance of RNA. Some look at RNA and see a "molecular fossil." I understand the perception, as I can see it too, but as more data keeps coming in, RNA looks more and more like a sophisticated molecule that represents an ingenious solution to a design problem. But that's getting far out into The Matrix.
Comment by MikeGene — September 2, 2006 @ 12:00 pm
September 2nd, 2006 at 12:57 pm
Okay, one more thing and I outta here.
Here's another nice synopisis of Eisen's research with some other links and comments.
Comment by MikeGene — September 2, 2006 @ 12:57 pm
September 3rd, 2006 at 7:41 pm
Mike wrote:
"It is important to keep in mind that I am not arguing for the reality of front-loading; I am still fleshing out the plausibility of front-loading."
Mike, you offered a hypothesis. The data are publicly available to test the hypothesis at ciliate.org. Why bother arguing in a blog when you can test your hypothesis right now?
"As such, your point is one that stimulates questions and potential research."
The questions can be answered today by BLASTing the sequences you'd expect to be front-loaded against the Tetrahymena genome. If you were a scientist, you'd be excited. Only a pseudoscientist would shy away from testing her/his hypothesis!
"The completed genome of Tetrahymena simply allows us our first good model to begin thinking along these lines (after all, we have very few sequenced single-celled eukaryotes, and even fewer that are free-living)."
Not just thinking, TESTING. Today. Get to it!!!
"The paper indicates there were 654 genes shared by Tetrahymena and humans, but not shared with other single-celled organisms. The families the researchers focused on were chosen for closer analysis because their propensity for expansion."
And none of those families fit the criterion required by your hypothesis. Whoops!
"I'd be more interested at looking more closely at all 654 genes to determine how closely they are associated with the multicellular state."
Why not do it, instead of arguing in a blog?
"And I think we can go beyond the detection of things such as hormone receptors, cell-cell adhesion proteins, etc."
In what way?
"But that's getting in The Matrix."
No, it's just using BLAST on the Web. Real scientists don't blog about their hypotheses when they can be tested immediately.
Comment by Smokey — September 3, 2006 @ 7:41 pm
September 3rd, 2006 at 7:45 pm
Mike wrote:
"Now you are starting to see how FLE can guide research."
No research needs to be guided. You just need to look at the extant data.
"A closer look is needed."
What's holding you up? The data are available for BLASTing at http://www.ciliate.org.
"So the evolution of "complex" multicellular organisms may have involved molecular stream-lining. Imagine that."
Imagine what? I didn't claim that complex multicellular organisms have fewer second-messenger pathways than ciliates.
Comment by Smokey — September 3, 2006 @ 7:45 pm
September 3rd, 2006 at 9:28 pm
blockquote> the elimination of histone protein H1 does not seem to have any deleterious effect in this protozoan, while H1 is essential in a complex metazoan state.
One has to be cautious about drawing such conclusions, particularly when dealing with creatures with a complex behavioral repertoire. It is worth noting that there are many genes that can be deleted in vertebrates with no apparent consequences, at least in a laboratory environment. But a laboratory environment does not reproduce the complexity encountered by a free-living organism, and the usual methods of study, while adequate to detect inviability, would not be expected to reveal a more modest selective advantage.
However, this doesn't answer the question of why it is retained. There are some microorganisms that have far more draconian junk-elimination systems (e.g. Neurospora). Evolutionarily, an efficient junk-elimination system would be expected to greatly slow the rate of evolution, and could increase the risk of extinction, but the question remains of why short-term selective advantage of junk elimination does not lead most organisms into an evolutionary cul-de-sac. One possibility is that the the macronucleus is not well-suited to reproduction, given that it carries a huge number of chromosomes and is polyploid to boot. So Tetrahymena may have found a mechanism of sequestering junk in such a way that selfish DNA poses little risk to the organism, and there is little selective advantage to eliminating it entirely.
The potential for limited evolution of the genetic code is not inconsistent with it being a "frozen accident." Evolution of the genetic code to co-opt a termination codon for an amino acid was observed in the early days of molecular biology, when such mutations were first known as "nonsense suppression mutants." The awkward way in which selenocysteine is kluged into the genetic code (which is not unique to Tetrahymena; we do it too), sharing a termination codon instead of having one to itself seems like a good example of a molecular "panda's thumb," reflecting the inherent difficulty of a late addition to the frozen accident of the genetic code.
I've spoken before about the folly of thinking of microorganisms as "simple." On the natural time-scale of evolution"”generations"”they are much, much older than we are. Cilliates such as Tetrahymena probably push the envelope of what can be achieved in a unicellular package. It doesn't seem at all surprising to me that they approach our genetic complexity.
Comment by trrll — September 3, 2006 @ 9:28 pm
September 3rd, 2006 at 10:30 pm
One has to be cautious about drawing such conclusions, particularly when dealing with creatures with a complex behavioral repertoire. It is worth noting that there are many genes that can be deleted in vertebrates with no apparent consequences, at least in a laboratory environment. But a laboratory environment does not reproduce the complexity encountered by a free-living organism, and the usual methods of study, while adequate to detect inviability, would not be expected to reveal a more modest selective advantage.
I agree with what trrll wrote but the selective value of the H1 of this particular species is an open question. This article passage is relevant:
Testing outcomes could lend credence to front loading or be used as evidence against it.
Comment by Bradford — September 3, 2006 @ 10:30 pm
September 4th, 2006 at 11:08 am
However, to test front loading, you need to be able to show that it generates predictions that diverge from those of the standard model of natural selection. That doesn't seem to be the case here.
In the standard model, gene families arise by duplication of an existing gene and divergence. Immediately after duplication, the copy is stabilized against loss by genetic drift by a modest selective advantage, either a gene dosage advantage or simply as a backup copy providing resistance to mutations that damage the original copy. Over time, the two genes co-evolve by acquiring mutations in their noncoding regulatory regions that fine-tune their temporal, spacial, or circumstantial patterns of expression, &/or by acquiring coding region mutations that modify their biological activities. The new gene may acquire a completely new function, or it may gradually take over some of the functions of the primary copy, allowing both genes to specialize and offer better service to a subset of the functions that they originally served.
So the standard model also predicts that genes which may confer a minor selective advantage in some species may become essential in others.
Comment by trrll — September 4, 2006 @ 11:08 am
September 4th, 2006 at 12:16 pm
Bradford wrote:
"Testing outcomes could lend credence to front loading or be used as evidence against it."
The most rock-solid prediction here is that no one who promotes ID will be doing any testing of anything.
Bradford, can you explain why Mike wouldn't look at the publicly available data before publishing a hypothesis?
How about you? Do you think that making your hypothesis fit the available data is a waste of time?
Comment by Smokey — September 4, 2006 @ 12:16 pm
September 4th, 2006 at 1:01 pm
Smokey:
Why are you so emotional? Why are you so impatient? I just told you that "I simply do not have the time for on-going involvement in this blog for the next few months." A reasonably intelligent person would realize this means I have become excessively busy recently. Yet you exploit the fact that my hands are tied to make demands on me. Are you taunting?
While I appreciate that you admit that my ID views are in fact testable, the testing you have in mind is just one form of testing I have in mind and is on my rather long list of "to do" things that can only be done in my spare time. You can help speed things up some if you want.
1. Do you have a paper or site that lists the multi-cellular signature proteins? If so, feel free to share it.
2. Do you have the list of the 654 protein-coding genes that are uniquely shared by humans and Tetrahymena? If so, feel free to share it.
Comment by MikeGene — September 4, 2006 @ 1:01 pm
September 4th, 2006 at 1:15 pm
Okay, since I'm here, one more brief response:
That's testing FLE against the "standard model." This is something that can come later as the perspective of FLE is better fleshed out. To flesh it out, what is in need of testing is the hypothesis that FLE is plausible; that a human-like intelligence, starting with nothing more than the first cells, can design evolution. When I first started thinking about FLE, many critics told me this was not even possible given the immense contingency and the myopia of the blind watchmaker. Those criticisms are being dealt with. Once the FLE perspective gets off the ground and raises novel insights and hypotheses that bear fruit, it will eventually be time to test it against the current paradigm. This is not something that will take place over a few days on an internet blog.
As it stands now, FLE and "the standard model" are simply two different perspectives on the same thing. While no non-teleologist should not feel obliged to adopt FLE (or even consider it), neither should any teleologist feel obliged to abandon it or ignore it.
Once again, I will remind people of the wise words from Jacob:
Comment by MikeGene — September 4, 2006 @ 1:15 pm
September 4th, 2006 at 1:39 pm
Sheesh. I knew I should not have looked in "“
Smokey, now you are spreading misinformation about me. In your mind, I "wouldn't" look at data and now you try to prime Bradford's mind with your loaded question.
I suggest you clean up your act.
Comment by MikeGene — September 4, 2006 @ 1:39 pm
September 4th, 2006 at 1:53 pm
It is trivially obvious that it is plausible. If natural selection can work from essentially random initial conditions, then obviously it can work with a "head start." So the first question is whether from a scientific standpoint, FLE is distinguishable from natural selection. In science, two theories that make identical predictions are regarded as equivalent, and the scientist, by convention, will use the simpler of the two. If question of whether FLE is distinguishable from natural selection is answered in the affirmative, then it would serve as a basis for answering the next question: "Is there any significant advantage to FLE over natural selection?"
Comment by trrll — September 4, 2006 @ 1:53 pm
September 4th, 2006 at 3:16 pm
If the loading point is the origin of life itself then the argument would focus on the adaquacy of natural selection. An outcome not explainable by natural selection would favor front loading.
Comment by Bradford — September 4, 2006 @ 3:16 pm
September 4th, 2006 at 5:26 pm
That's pretty much untestable. To show such a thing, it would be necessary to identify every possible natural selection pathway from every possible origin point, determine fitness at every step, and shown that there is no path to the outcome through this enormous, multidimensional configuration space that does not encounter a major low-fitness chasm. Among other things, such a determination would require the ability to calculate fitness based upon DNA sequence data, which would require the ability to calculate protein folding and activity from sequence, as well as the physiological and behavioral consequences for the organism, and determine their effects on inclusive fitness in all possible environmental contexts. This is enormously beyond the bounds of conceivable computation capability for the foreseeable future, essentially requiring the ability to simulate, not merely the entire biology of an organism, but an entire ecosystem. So if the only prediction that you can make is a negative one like "natural selection is not enough," then you are at a dead end. To have a viable research program, you need to come up with positive predictions that diverge from those of natural selection.
Comment by trrll — September 4, 2006 @ 5:26 pm
September 4th, 2006 at 11:43 pm
That's pretty much untestable. To show such a thing, it would be necessary to identify every possible natural selection pathway from every possible origin point, determine fitness at every step, and shown that there is no path to the outcome through this enormous, multidimensional configuration space that does not encounter a major low-fitness chasm.
One of the difficulties with OOL is that proposed pathways are either imaginary constructs or indications that different biochemical building blocks form in differing conditions of extra-cellular environments. The problem is that it neither enhances or detracts from competing ideas. The begining of the story may not ever be nailed down in detail but at the end lies a replicating cell containing networks of interacting proteins coded for by nucleic acids. No stochastic process has been suggested that is linked to natural selection.
Among other things, such a determination would require the ability to calculate fitness based upon DNA sequence data, which would require the ability to calculate protein folding and activity from sequence, as well as the physiological and behavioral consequences for the organism, and determine their effects on inclusive fitness in all possible environmental contexts.
The problem is not as hopelessly open ended as you portray it. DNA sequence data is linked to function and cellular data can be organized into functional hierarchies. At the base would lie functional nucleic acid, protein synthesis mechanisms and metabolic pathways. There are natural constraints within which the problem can be analyzed. The real problem is not overwhelming data but rather a reason to believe a selection sifter exists.
This is enormously beyond the bounds of conceivable computation capability for the foreseeable future, essentially requiring the ability to simulate, not merely the entire biology of an organism, but an entire ecosystem. So if the only prediction that you can make is a negative one like "natural selection is not enough," then you are at a dead end.
It is not a matter of natural selection not being enough. Natural selection is a logical constuct at this level. There is no convincing data indicating that selection provides a directional pathway toward a cell. I left out your last sentence not because it is without merit. To the contrary is deserves a more detailed answer than I have time for at the moment.
Comment by Bradford — September 4, 2006 @ 11:43 pm
September 5th, 2006 at 1:03 pm
I wouldn't say that the proposed pathways are "imaginary constructs," considering that a number of them are under active laboratory investigation. While researchers still seem to be quite some way from creating a replicating "life form" simple enough to have evolved under a plausible set of prebiotic conditions, progress continues to be made, and there is no indication that the field has hit any kind of "dead end." Considering the extremely wide range of plausible prebiotic conditions, there are a huge number of possibilities to be examined, so there's not much prospect of the field running dry any time soon. Scientists certainly are not going to abandon an active field that is giving rise to significant discoveries in favor of a purely hypothetical notion of life being seeded from an external source, unless that hypothesis can be fleshed out enough to generate solid predictions that can be tested in the lab.
Of course, there are some things that may be beyond the reach of laboratory studies. While it is likely that simple, self-replicating organisms will eventually devised, it is doubtful whether we'll ever know for sure which started off the process, and the evolution of later developments, such as the DNA/RNA/protein system, may never be known in any real detail.
Does anybody reasonable deny that a "selection sifter" exists? After all, evolution of novel enzymatic activities has been demonstrated in the laboratory. One could reasonably argue about whether this mechanism explains everything, but it clearly exists. Even front-loaded evolution relies heavily upon selection based mechanisms"”it just hypothesizes that somebody has primed the pump.
Unfortunately, the functional constraints upon the relationship between DNA sequence and function are not sufficient to predict the effect on fitness of a particular mutation, especially since fitness will depend also upon all of the other components of the cell. So the likelihood of being able to evaluate possible evolutionary pathways on a mutation-by-mutation basis is certainly nil for the foreseeable future.
It's not clear that any direction is needed to get to something like a cell. Cell-membrane like structures form and reproduce spontaneously under various conditions and can either trap or accumulate other types of molecules. So there may have been a variety of cell-like structures around even without selection. All that is needed for selection to kick in is for the reproduction of some of these protocells to be influenced by their contents.
Comment by trrll — September 5, 2006 @ 1:03 pm
September 5th, 2006 at 2:06 pm
Mike wrote:
"Why are you so emotional? Why are you so impatient?"
If I had a test of one of my hypotheses about gene homologies made available to me, the last thing I'd do is blog about it. I'd be very impatient and start BLASTing right away.
"I just told you that "I simply do not have the time for on-going involvement in this blog for the next few months.""
It's not about the blog! Why would blogging come before BLASTing?
"A reasonably intelligent person would realize this means I have become excessively busy recently."
Not too busy to blog, obviously! My question is, why would BLASTing come second to blogging? If I were you and didn't know how to use these sorts of tools, I would ask for help in my blog.
"While I appreciate that you admit that my ID views are in fact testable,…"
Only one of them, AFAIK. I made no general statement. Moreover, it was Krauze's view IIRC.
"… the testing you have in mind is just one form of testing I have in mind and is on my rather long list of "to do" things that can only be done in my spare time."
But why would it come before blogging? After all, the Templeton Foundation offered grants:
"1. Do you have a paper or site that lists the multi-cellular signature proteins? If so, feel free to share it."
Why would there be such a list? It's a judgment call, but you can control for bias by coming up with a list before BLASTing.
Another consideration is that Tetrahymena does have a multicellular phase–conjugation, so anything found to be involved in that doesn't argue for front-loading. You could rotate that to the end as a post-BLAST test if you were pressed for time.
Finally, off the top of my head, lots of vertebrate proteins only involved in intERcellular events are highly modular, and many of those modules are likely to have intRAcellular functions. This can be used as an internal control, as an absence of front-loading predicts that one will find homology to human intERcellular proteins predominantly in those modules that also are involved in intRAcellular functions. You will still get hits!
"2. Do you have the list of the 654 protein-coding genes that are uniquely shared by humans and Tetrahymena? If so, feel free to share it."
The data are at http://www.ciliate.org, remember?
You also could start with this shorter list of disease-related genes:
http://biology.plosjournals.or...
I predict that genes encoding inter- and extracellular proteins in humans will be grossly underrepresented on that list, relative to human disease genes as a whole (or the same number of human disease genes selected at random).
Front-loading makes a different prediction, no?
I wrote, "Bradford, can you explain why Mike wouldn't look at the publicly available data before publishing a hypothesis?
"Smokey, now you are spreading misinformation about me. In your mind, I "wouldn't" look at data and now you try to prime Bradford's mind with your loaded question."
If you did analyze the sequence data, my apologies.
If so, what did you find, and why didn't you include it in your post? If not, I don't see any misinformation.
Comment by Smokey — September 5, 2006 @ 2:06 pm
September 6th, 2006 at 5:10 am
Does anybody reasonable deny that a "selection sifter" exists? After all, evolution of novel enzymatic activities has been demonstrated in the laboratory. One could reasonably argue about whether this mechanism explains everything, but it clearly exists. Even front-loaded evolution relies heavily upon selection based mechanisms"”it just hypothesizes that somebody has primed the pump.
Biological novelties acquire meaning when context is considered. A novel enzyme can confer function because there exists a substrate. There must also exist a gene that codes for the enzyme if the novelty is to be selected and passed on to descendents. This in turn entails the need for a supporting structure that includes a genome capable of allowing for the synthesis of the enzyme in question as well as the replication of the relevant nucleic acid and encompassing cellular structure. The theme of minimal function dominates the landscape. It is not at all evident that a selection process gets one to minimal biological function. Selection itself is the tested concept.
Unfortunately, the functional constraints upon the relationship between DNA sequence and function are not sufficient to predict the effect on fitness of a particular mutation, especially since fitness will depend also upon all of the other components of the cell. So the likelihood of being able to evaluate possible evolutionary pathways on a mutation-by-mutation basis is certainly nil for the foreseeable future.
You have correctly identified the main issue. Fitness is multi-component dependent. And the significance of this is not lost on IDers. Selection is an inherently incremental process and biological mechanisms inherently multi-component in nature. Adjustments are not problematic as long as a cell is in place but a cellular automon and an encoding descriptor must exist at the outset as well as a means of predicting what copying errors are selected and why. The RNA world is a paradigm lacking predictive utility.
It is not a matter of natural selection not being enough. Natural selection is a logical constuct at this level. There is no convincing data indicating that selection provides a directional pathway toward a cell.
It's not clear that any direction is needed to get to something like a cell. Cell-membrane like structures form and reproduce spontaneously under various conditions and can either trap or accumulate other types of molecules.
Far from being an obvious advantage a lipid membrane, lacking embedded proteins, that traps molecules, could be distinctly disadvantagous. Whatever is trapped inside better be sufficient to function or evolve a function.
So there may have been a variety of cell-like structures around even without selection. All that is needed for selection to kick in is for the reproduction of some of these protocells to be influenced by their contents.
Which begs the question of why this scenario is plausible in the first place.
Comment by Bradford — September 6, 2006 @ 5:10 am
September 6th, 2006 at 6:00 pm
No, genes are not a requirement for evolution. There must exist some mechanism for manufacturing the enzyme (or other biological catalyst, such as ribozyme), and that mechanism must be subject to mutation capable of altering the structure of the enzyme. There is no reason that mechanism needs to be gene-based.
Even modern membranes trap certain types of molecules quite independently of their protein content. Some molecules move freely across the membrane, some are impermeant or very slowly permeant, and some move across the membrane depending upon pH. It is certainly true that whatever is trapped inside needs to enhance vesicle replication as well as manufacture from permeant "nutrients" those factors that enhance membrane vesicle replication (since otherwise they would be diluted out as the vesicle replicates). On the positive side, that right mix only has to happen once, because the result would be a proto-organism capable of reproducing and undergoing selection.
Comment by trrll — September 6, 2006 @ 6:00 pm
September 6th, 2006 at 6:25 pm
Based on available data, what supporting evidence are you able to cite of a mechanism that both enables enzyme synthesis and a replication capacity needed to pass on selected information to descendents?
Comment by Bradford — September 6, 2006 @ 6:25 pm
September 8th, 2006 at 1:11 am
Enzymes can manufacture peptides without the need for nucleic acid. Changes in enzyme sequence can alter catalytic specificity. Catalytic activity can be found even in random polypeptides and nucleic acids. So a replication system along the lines of "peptide A catalyzes synthesis of peptide B, peptide B catalyzes synthesis of peptide A" is clearly possible.
Comment by trrll — September 8, 2006 @ 1:11 am
September 8th, 2006 at 2:19 am
Bradford wrote:
"A novel enzyme can confer function because there exists a substrate. There must also exist a gene that codes for the enzyme if the novelty is to be selected and passed on to descendents."
Why can't one (or evolution) make a novel enzyme by, say, a single amino-acid substitution in an existing enzyme that allows it to recognize a new substrate without losing the ability to recognize the original substrate? Then the gene already exists, right?
Comment by Smokey — September 8, 2006 @ 2:19 am
September 8th, 2006 at 9:04 am
Enzymes can manufacture peptides without the need for nucleic acid. Changes in enzyme sequence can alter catalytic specificity. Catalytic activity can be found even in random polypeptides and nucleic acids. So a replication system along the lines of "peptide A catalyzes synthesis of peptide B, peptide B catalyzes synthesis of peptide A" is clearly possible.
You've avoided addressing the thrust of my question which relates to the capacity to convey a trait to descendents. If the descendents in this hypothetical are random peptides then there is no selection criteria. There also is no means of generating a reliable supply of amino acids.
Comment by Bradford — September 8, 2006 @ 9:04 am
September 8th, 2006 at 11:06 am
There are plenty of examples of polypeptides made by proteins without utilizing the ribosomal assembly line. And it is well established that changes in sequence can alter specificity. So there is no biological reason why inheritance could not be based purely upon catalysis, without the need for a separate information storage medium such as DNA.
Comment by trrll — September 8, 2006 @ 11:06 am
September 8th, 2006 at 11:14 am
While the process would start with random peptides or nucleic acid, peptide/nucleic acid catalysis would cause substequent generations to be less and less random, favoring the populations whose synthesis is catalyzed by those sequences that happened to be trapped in the original protocell. If that population enhances the stability, growth, and reproduction of the protocell, selection will take place among protocells. Amino acids are made by a number of prebiotic processes, so these would constitute the natural "food" of the protocell.
Comment by trrll — September 8, 2006 @ 11:14 am
September 8th, 2006 at 12:53 pm
I'm not letting you get away with explanations that selectively ignore data. Of course changes in sequence can alter specificity but you have not built the case for inheritance in the absence of a storage medium. In fact what the data indicates is extinction of the process occuring at a point where the supply of amino acids is exhausted or nucleotides in the case of a hypothesized RNA catalyst.
There is nothing to distinguish this from a science fiction story. There is lack of specificity as to causal factors that would generate the listed outcomes.
Amino acids are found scattered among a much larger amount of organic sludge in spark discharge experiments. An enclosed membrane further adds to the theoretical problems.
Comment by Bradford — September 8, 2006 @ 12:53 pm
September 8th, 2006 at 2:31 pm
So the standard model also predicts that genes which may confer a minor selective advantage in some species may become essential in others.
But the standard model does not argue that functionless genes have selective value. If it claims to encompass that scenario then it loses explanatory value which a better explanation does not do.
Comment by Bradford — September 8, 2006 @ 2:31 pm
September 8th, 2006 at 5:18 pm
However, as pointed out in the passage you quoted
But the standard model does not argue that functionless genes have selective value. If it claims to encompass that scenario then it loses explanatory value which a better explanation does not do.
However, as the passage you quote notes
In other words, front loading also does not predict the existence of functionless genes; indeed, they are required to have selective value to prevent them from being lost by drift before they are passed down to the organisms that will have use for them.
Moreover, as I pointed out before, the fact that a protein is not essential in a particular laboratory context does not tell you that it is without selective value for a free-living organism.
Comment by trrll — September 8, 2006 @ 5:18 pm
September 8th, 2006 at 5:52 pm
A protein is itself a storage medium"”a sequence of amino acids. You have not built a case for the requirement for a secondary storage medium. "But all modern cells have it" is not a valid argument.
Yes, creatures will starve when they run out of food. So once proto-organisms reproduce to the point that they begin to deplete their food source (prebiotic nucleic acids and or amino acids) there will be a strong selective advantage to those that have the ability to steal or manufacture them.
What causal factors? Catalytic activity can be found in mixtures of random peptides or nucleic acid polymers. With random selections of such polymers, you will in some cases get autocatalytic subsets of polymers that can "close the circle," catalyzing one another's synthesis. The statistics have been worked out by Stuart Kauffman
Amino acids even turn up in meteors. It is clear that there are multiple ways to get amino acids without biology.
Nonbiological formation of membrane like structures has also been demonstrated.
Comment by trrll — September 8, 2006 @ 5:52 pm
September 8th, 2006 at 7:37 pm
In other words, front loading also does not predict the existence of functionless genes; indeed, they are required to have selective value to prevent them from being lost by drift before they are passed down to the organisms that will have use for them.
Perhaps Mike Gene's front loading concept does not predict them but they are consistent with the idea that their value lies with long term purposeful planning. As you indicate a lack of selective value is not consistent with retention under a natural selection paradigm.
Comment by Bradford — September 8, 2006 @ 7:37 pm
September 8th, 2006 at 8:00 pm
It is a better argument than one based on hope or imagination. It is what we are able to see and evaluate. Moreover protein function is not analogous to the coding function of nucleic acids except by grotesque distortion of reality.
In fact what the data indicates is extinction of the process occuring at a point where the supply of amino acids is exhausted or nucleotides in the case of a hypothesized RNA catalyst.
You evade the problem of amino acid sources by simply skipping to a point where organisms are reproducing without dealing with the real obstacles to the undemonstrated self-assembly process. There are no adaquate sources of amino acids found outside cellular environments.
There is nothing to distinguish this from a science fiction story. There is lack of specificity as to causal factors that would generate the listed outcomes.
Statistics, schmatistics. When you can do it in a lab you don't need to rely on algorithms and stats to make a case. Catalysts are substrate specific. Amino acids and codon recognition are the specific issues needing to be addressed. We're not just talking about any polymers. There are information storage and translation functions involving codons that do not fade away with generalizations about catalysis.
Amino acids are found scattered among a much larger amount of organic sludge in spark discharge experiments. An enclosed membrane further adds to the theoretical problems.
The absence of just one aa in a sequence can be enough to disable function. Protein function is too sequence dependent to toss off with meteor references. In exchanges like this METers are like chamelions wielding precise references when to their advantage and when not sounding very much like spin meisters.
Comment by Bradford — September 8, 2006 @ 8:00 pm
September 8th, 2006 at 11:42 pm
You mean aside from prebiotic chemical synthesis and meteors? One large meteor in a lake might be able to deposit enough amino acids to keep protolife forms going quite a while, giving them time to evolve their own synthetic mechanisms.
The difference is that these hypotheses have led to active research, which has already confirmed a number of predictions. Again, this review includes citations to much of the experimental literature.
Yes, it is nice to be able to do things in the lab. But that is only one of many methods of testing scientific hypotheses.
Some catalysts have tight substrate specificity, others accept a wide range of substrates. It is likely that the earliest catalysts fell into the latter category.
On the contrary, an enclosing membrane turns a collection of organic peptides into a unit subject to selection, solving a major theoretical problem.
Codons are likely rather late additions. They aren't a big advantage for a simple procell with a simple autocatalytic metabolism. But with selection favoring more efficient organisms, there would be a driving force for evolution of this kind of "robotic assembly line," which makes it possible to greatly diversify cellular proteins.
Can be? Occasionally. But in reality, it often is not, as many mutagenesis studies have shown. For most amino acids in a sequence, there are a lot of variations that can be made without loss of function.
Comment by trrll — September 8, 2006 @ 11:42 pm
September 9th, 2006 at 1:13 pm
No, genes are not a requirement for evolution. There must exist some mechanism for manufacturing the enzyme (or other biological catalyst, such as ribozyme), and that mechanism must be subject to mutation capable of altering the structure of the enzyme. There is no reason that mechanism needs to be gene-based.
Synthesis of biomolecules is an information based process. So too is the transference of that information to descendents. This illustrates the intellectual bankruptcy of mechanistic paradigms:
Comment by Bradford — September 9, 2006 @ 1:13 pm
September 9th, 2006 at 6:05 pm
Smokey:
That's easy. How long did it take me to write up that blog? Months? No. Weeks? No. Days? No. Hours? No. I took me about 30 minutes. Given that it will take me a whole lot more than 30 minutes to do any serious BLASTing and analysis, your question is nonsensical.
You write:
I see. So the first thing I should do before blogging is ask the question "“ WWSD? (What Would Smokey Do?). Yet since our personalities and obligations probably differ significantly, why in the world would you project your proclivities upon me? Do you think the world was made in your image? I'm sorry, but I am not nearly as impulsive and impatient as you. As you know, I have long viewed ID as my intellectual hobby and this hobby has accumulated a lot of things on my "to do" list over the years, things that must be done in my spare time. I have to be patient, otherwise, I'd have to throw it all away. So the genome data will always be there, the hypotheses and ideas are scribbled down, there is no need to do the analysis "all at once," and the time will come when the time comes.
But since you preach loudly about testing, I took your advice and tested your sincerity. If you truly wanted me to test instead of blog, I asked you to provide a couple of pieces of information that would help me speed things up. Bottom line? You failed to come through, Smokey.
So let's summarize. I told everyone my time was extremely limited. The scientist ignored that data point. The scientist then demanded that I conduct a massive BLAST analysis in the same time it takes me to write up a blog. The scientist wouldn't help speed things up, as the scientist couldn't provide me with a list of multi-cellular signature proteins. The scientist also couldn't provide me with a link to the 600+ protein-coding genes that are shared unique by this protist and humans.
So why is Smokey here? He has made it clear he thinks ID is nonsense. And knowing people, they don't seriously engage in open-minded discussions with others perceived to be espousing nonsense. Smokey is thus here with a closed-mind and an agenda. His agenda? To ensure, in his mind, that reality conforms to his stereotypes. Remember the stereotypes, people. If you do not agree that ID is nonsense, this means you are stupid, dishonest, or mentally unbalanced. The goal of the critic is to then fit his opponents into one (or more) of these categories.
Smokey gives this approach away with two comments: 1) "Only a pseudoscientist would shy away from testing her/his hypothesis!," and 2) "If I were you and didn't know how to use these sorts of tools, I would ask for help in my blog."
In other words, Smokey's question/demand is simply an expression of his stereotypes. That's what is has been all about.
Comment by MikeGene — September 9, 2006 @ 6:05 pm
September 9th, 2006 at 10:09 pm
MikeGene, as a psychologist, I can confirm that there's no evidence that you fit any diagnostic category. I guess that leaves only stupid (which my naive impression easily dismisses) or dishonest…which I suppose would be up to Smokey. Smokey…do you have any evidence of dishonesty?
Comment by Lutepisc — September 9, 2006 @ 10:09 pm
September 10th, 2006 at 2:09 pm
Mike wrote:
"Given that it will take me a whole lot more than 30 minutes to do any serious BLASTing and analysis, your question is nonsensical."
Since you can BLAST in far less time, my question makes infinite sense.
"I see. So the first thing I should do before blogging is ask the question "“ WWSD? (What Would Smokey Do?)."
No. If your approach is scientific, the first thing you'd do is examine the data to see if your hypothesis was supported or contradicted. That would be your motivation, not mimicking what I'd do.
"Yet since our personalities and obligations probably differ significantly, why in the world would you project your proclivities upon me?"
Do you not claim that your approach is scientific? If so, our proclivities should be the same.
"… As you know, I have long viewed ID as my intellectual hobby and this hobby has accumulated a lot of things on my "to do" list over the years, things that must be done in my spare time."
Whether it is a hobby or profession is orthagonal to my question of whether your approach is scientific or pseudoscientific.
"I have to be patient, otherwise, I'd have to throw it all away. So the genome data will always be there, the hypotheses and ideas are scribbled down, there is no need to do the analysis "all at once," and the time will come when the time comes."
So why blog, when you can do multiple BLASTs in the same amount of time?
Did you consider taking the human disease-related genes that have homology with Tetrahymena but not yeast and just looking them up on OMIM? The MS Word file supplies the OMIM numbers.
"But since you preach loudly about testing, I took your advice and tested your sincerity. If you truly wanted me to test instead of blog, I asked you to provide a couple of pieces of information that would help me speed things up. Bottom line? You failed to come through, Smokey."
No, I offered a lot of information, remember?
"So let's summarize. I told everyone my time was extremely limited. The scientist ignored that data point."
False. The scientist pointed out that you had sufficient time to blog, which takes far more time than multiple BLASTs.
"The scientist then demanded that I conduct a massive BLAST analysis in the same time it takes me to write up a blog."
False again. I didn't propose a "massive" BLAST analysis. In fact, I proposed a sampling of the disease-related genes from the group, and supplied a link to a MS Word file.
"The scientist wouldn't help speed things up, as the scientist couldn't provide me with a list of multi-cellular signature proteins."
As I said, that's a judgment call.
"The scientist also couldn't provide me with a link to the 600+ protein-coding genes that are shared unique by this protist and humans."
True. You said that your time was limited, so instead of ignoring that, I pointed you to a subset instead:
http://biology.plosjournals.or...
"He has made it clear he thinks ID is nonsense."
I think that pseudoscience is nonsense, and I have been looking for a single person who takes a scientific approach to the notion of ID.
You clearly aren't one of them.
"And knowing people, they don't seriously engage in open-minded discussions with others perceived to be espousing nonsense."
I'm testing the hypothesis that ID advocates are pseudoscientific. That requires open-minded data gathering. If you had expressed interest in BLASTing instead of adding the adjective "massive," I would be very open to that.
"Smokey is thus here with a closed-mind and an agenda."
False and true, respectively.
"His agenda? To ensure, in his mind, that reality conforms to his stereotypes."
False. To test the hypothesis that all ID advocates use a pseudoscientific approach. So far, it's holding up.
"Remember the stereotypes, people. If you do not agree that ID is nonsense, this means you are stupid, dishonest, or mentally unbalanced."
I'd disagree. Many smart people are taken in by pseudoscientific nonsense, too. In fact, it is so prevalent as to be normal.
"Smokey gives this approach away with two comments: 1) "Only a pseudoscientist would shy away from testing her/his hypothesis!," and 2) "If I were you and didn't know how to use these sorts of tools, I would ask for help in my blog.""
How are those inconsistent with my stated agenda?
"In other words, Smokey's question/demand is simply an expression of his stereotypes. That's what is has been all about."
No, it's about testing a hypothesis. If the hypothesis fits everyone in the category, the stereotype is correct.
Comment by Smokey — September 10, 2006 @ 2:09 pm
September 10th, 2006 at 2:28 pm
Lutepisc wrote:
"MikeGene, as a psychologist, I can confirm that there's no evidence that you fit any diagnostic category."
Interesting. That brings up 2 points:
1) I didn't claim that Mike fit any diagnostic category, and
2) according to the The Ethical Principles of Psychologists and Code of Conduct of the American Psychological Association:
So, if you are an ethical psychologist, you must have examined her/him as well as obtaining her/his permission to discuss your diagnosis with others before publishing such a statement, correct?
"I guess that leaves only stupid (which my naive impression easily dismisses) or dishonest"¦which I suppose would be up to Smokey. Smokey"¦do you have any evidence of dishonesty?"
You're a psychologist and you're not familiar with the ubiquity of deception and self-deception in normal humans, the very reason we codify our scientific method?
Amazing.
Comment by Smokey — September 10, 2006 @ 2:28 pm
September 16th, 2006 at 11:36 am
Smokey:
No it doesn't. It is one thing to cut and paste a sequence and BLAST it. But such trivial actions are not all that meaningful by themselves. It is quite another thing to BLAST a set of sequences as part of a systematic analysis. You yourself know this. Remember writing this?
I didn't add the emphasis on 'before.' And first coming up with a list is just one thing to do. I also plan to spend some time looking up what each gene does, categorizing them, etc., in order to properly interpret the results of BLAST. All of this will take far, far more time that writing up that blog. That's a simple fact and you know it.
Sure. As I explained before, at this stage, we are simply feeling out the possibilities and plausibility of FLE. Sorry Smokey, but you will just have to deal with the fact that I am inspired by Francois Jacob's experience and wisdom and not by your taunts. It was the Nobel Laureate Jacob who noted:
To make a valuable observation about these things will indeed require "looking at objects from a different angle." That perspective is being fleshed out and the blog that troubles you is part of the developing perspective. BLASTing will come when it comes (and it is indeed part of the plan). At that point, will you publicly acknowledge that my perspective is scientific?
Please define "scientific" and show where I claim that my approach fits your definition.
I do not subscribe to such either/or thinking. Why think that all approaches that are non-scientific are pseudo-scientific? Where is the room for proto-scientific? Where is the room for quasi-scientific? Why not just non-scientific? Let's go back to the wisdom of the Nobel Laureate: "It always involves a certain conception about the unknown, that is, about what lies beyond that which one has logical or experimental reasons to believe." Does this mean science is born in the soil of pseudo-science?
I have already answered your question. It's now turn for you to answer your own question.
So why do you comment so much on an ID blog when you can be doing experiments in the same amount of time?
If you complain about one who blogs instead of doing experiments, what does that make the person who continually complains in the comments section of that blog instead of doing experiments?
Yep.
Your information was not helpful (as I could get that myself) and not the type of information I was looking for.
But that didn't answer my question.
And that didn't answer my questions.
Irrelevant. The information that I would retrieve from less than 30 min of BLASTing would be insufficient for what I have in mind.
I see. So you just want me to BLAST a small number of sequences that were chosen willy-nilly. And just what would this accomplish?
Yep, with 58 sequences. That gives me a whole 30 sec per gene for BLAST analysis. Sorry, but it is simply a fact that it will take me a lot longer than 30 seconds to consider each gene. That's why your demand is nonsensical.
Exactly. And making judgment calls also take time.
Yep, with 58 sequences. That gives me a whole 30 sec per gene for BLAST analysis. Sorry, but it will take me a lot longer than 30 seconds to consider each gene. That's why your demand is nonsensical.
So what? Are you telling us that your non-teleological perspective is such a dry hole that you have all this time to search the world for "a single person who takes a scientific approach to the notion of ID?" Why is the quest so important to you? Are you haunted by ID and thus must reassure yourself that anyone who doesn't think it is nonsense is an eevil pseudo-scientist?
LOL. Well, according to you, the test results are in. So, what's next? If you are sincere, you shall be leaving Telic Thoughts. Bye bye. If you hang around and keep arguing, we'll know the "testing" excuse is not sincere.
It troubles you that I would want to look at all 654 genes? Why?
Me: "Smokey is thus here with a closed-mind and an agenda."
You preach about the "ubiquity of deception and self-deception in normal humans" as "the very reason we codify our scientific method." Well, that might every well include you, Smokey, so let's see if you beliefs about yourself have been verified by this codified method.
Now, I am sure you like to think of yourself as being open-minded about this issue, but as man who wears his science on his sleeves, you certainly can't expect us to believe this on faith. As it stands, from my perspective, there is not a scrap of evidence to support your open-minded self-perception.
So we now have a new hypothesis about our physical world on the table "“ "When it comes to the issue of ID, Smokey is open-minded."
Since Smokey preaches so much about testing and the need to be "scientific," this belief of his must have been the result of scientific testing. So Smokey should share a) the tests he conducted to determine he is open-minded and b) the results/evidence that supports his hypothesis about himself.
On the other hand, could it be possible that the belief, "Smokey is open-minded about ID" is itself an expression of pseudo-science?
Okay, since your non-teleological approach doesn't seem capable of keeping you busy in the lab, you have turned to sociological research. Since you are going to extrapolate to "all" from a limited sample, would you care to tell us how you scientifically came to choose your samples? Are you doing a statistical analysis? Do you have controls? And will you publish your findings in the peer-reviewed literature?
Me: "Remember the stereotypes, people. If you do not agree that ID is nonsense, this means you are stupid, dishonest, or mentally unbalanced."
That's why I wrote "or." Take away one leaves two. So what is there you disagree with again?
Here is your idea of "testing a hypothesis." Surf the internet and get into arguments. If you find someone who blogs in 30 minutes instead of BLASTing and analyzing 58 gene sequences during that time, you've found data that supports your hypothesis. It's call confirmation bias.
Comment by MikeGene — September 16, 2006 @ 11:36 am
September 19th, 2006 at 7:33 pm
BLASTing a sequence is trivial by itself?
And the 58 were chosen systematically.
But as I pointed out, you can simply categorize the OMIM list and skip the BLAST. But if you want to categorize them before, I'll be happy to help.
But now you've jumped the shark by arguing with me instead of doing it.
It looks to me like you're making excuses to justify a twisted prioritization that avoids testing.
It looks to me like he's talking about choosing projects and hypotheses, not testing them. But if you wanna go by his experience, did Jacob write a whole book of "feeling out" and "plausibility" before he rigorously tested his hypotheses?
The blog doesn't trouble me. The fact that you have time to argue on your blog, but none to test a hypothesis is the subject of our discussion.
Only when you execute the plan, and only if the plan includes rock-solid methods to preclude confirmation bias.
I wrote: Whether it is a hobby or profession is orthagonal to my question of whether your approach is scientific or pseudoscientific.
That's funny! If you don't subscribe to eitheror/ thinking, why is it that you are taking the position of either "feeling out" or testing hypotheses, and the former prevents allocation of any time for the latter?
Within scientific, of course.
No. You're forgetting that it always involves testing of hypotheses.
Because I have time to do both. I'm not an either/or gal/guy like you!
I don't. I question those who claim that blogging precludes testing hypotheses.
So it's an either/or thing?
You don't see, because they weren't chosen willy-nilly. It would accomplish a preliminary test of the hypothesis.
Why would it take longer than 30 seconds to use the OMIM numbers to learn the identity of each one?
No, they take judgment.
Nope. My perspective works well enough so that I have grants and papers.
Nope. I'm interested in science education.
No, just a datum.
How do YOU justify arguing if you lack the time to test your hypothesis?
It sounds like an excuse to avoid looking at any of them.
Absolutely. That's why I design experiments so that self-deception is not a factor; stuff like blinding myself to which samples are controls or experimentals before analyzing them.
Sorry, Mike, but I'm not the one claiming that I lack the time to test my hypotheses. You look silly trying to project your excuse onto me.
Possibly. I have one such paper already from a course I co-taught on pseudoscience.
Mike: "Remember the stereotypes, people. If you do not agree that ID is nonsense, this means you are stupid, dishonest, or mentally unbalanced."
Smokey: I'd disagree. Many smart people are taken in by pseudoscientific nonsense, too. In fact, it is so prevalent as to be normal.
One can be smart, honest, and mentally balanced, and still be taken in by pseudoscience. It happens all the time.
Nope. Find one of the rare ID proponents who bothers to offer a testable hypothesis and see if she/he is actually willing to test it.
Nope. You forgot to mention that you claim that you lack the time to test a hypothesis, and you've spent much more time desperately trying to pretend that I claimed the same time limitation for myself.
Comment by Smokey — September 19, 2006 @ 7:33 pm
September 19th, 2006 at 7:36 pm
Whether lack of tolerance for sequence variation exists is a matter for testing not debating.
"¦and my reference is an OOL scenario, the enzyme context means everything.
The context here is both in vitro and in vivo. The in vitro condition is just a buffer with potassium, sodium, and magnesium salts, as well as the substrate.
Variation of enzymes is observed in cells of living organisms. Generation of multi-component functions involving enzymes is relevant to this environment but not to a prebiotic one. Experimental results are consistent with this statement. The applicability of in vitro references, to the generation and subsequent variation of functionally specified enzymes in a prebiotic environment, is entirely speculative.
You either are trolling or engaged in deliberate distortion.
How do you figure? Did you not claim:
"There must be a balance between fidelity and errors. A complete absence of the latter terminates an evolutionary process and too little of the former compromises function. A related prediction is that function enabled by specific nucleotide sequences is lost in the absence of error detection and repair mechanisms. Unless there are existing genes, that code for RNA and proteins required by such mechanisms, genomes decay and become non-functional."
There you are. I asked you about HeLa cells"“have they lost "function enabled by specific nucleotide sequences" "in the absence of error detection and repair mechanisms"
Why didn't you respond?
What is your specific question?
If you're so sure that errors cause genomes to decay and nonfunctional, wouldn't you need to know something about the level of sequence specificity required to maintain function?
The relevant function is cellular replication. If you wish to contend that ancient cells were much less complex than modern ones- fine- just support your contention with data.
Enzymes, substrates and biological function do not arise (which includes a means of storing information and passing it to descendents) from a prebiotic starting point
What does this have to do with a prediction? I'm simply asking you why you are afraid to apply your general assumption,
"The lack of tolerance for sequence variation"¦" to a specific case.
Apply it to E.coli or your organism of preference. E.coli has, if I remember correctly, 32 genes identified as coding proteins involved in ed&r mechanisms. The lack of a partial subset of these should suffice to show a lack of tolerance for variance in their absence.
Comment by Bradford — September 19, 2006 @ 7:36 pm