I am submitting this week a manuscript by me entitled “The overlap feature of the genetic equidistance result, a fundamental biological phenomenon overlooked for nearly half a century”. The work establishes an overlooked feature of a fundamental result that directly triggered the molecular clock and neutral theory, the dominating theory in the field of molecular evolution. If this old result had been correctly interpreted from the beginning, we would have seen a very different half-century of research on the molecular record of evolution. Epigenetics should have an important role to play in the hereditary transformation of life forms and hence in a complete theory of evolution. It is time to incorporate epigenetic into the field of evolution. Indeed, many facts of evolution simply cannot be explained without epigenetics, including the old result that directly triggered the field of molecular evolution.
Abstract
The genetic equidistance result shows that different species are approximately equidistant to a simpler outgroup in sequence similarity, as first reported by Margoliash in 1963. This result, together with those of Zuckerkandl and Pauling in 1962, inspired the molecular clock and in turn the neutral theory. Here, it is shown that the clock/neutral theory had from the beginning overlooked another characteristic of the equidistance result, the overlap feature, which shows a large number of overlapped mutant positions where any pair of any three species is different provided that the species concerned differ from one another in complexity as a result of macroevolution. In contrast, when simple organisms of similar complexity and of short evolutionary divergence are compared, there are only a small number of overlaps largely consistent with chance or the neutral theory. Thus, the overlap feature is one of the best pieces of evidence for a clear distinction between macroevolution and microevolution. The full reality of the equidistance result strongly supports the Maximum Genetic Diversity Hypothesis, a more complete account of hereditary changes based on an inverse relationship between genetic diversity and epigenetic complexity.
P.S. The manuscript defines more clearly the overlap feature and corrects some minor errors in my earlier posts on the overlap feature.
Friday, December 11, 2009
What CNE means for the neutral theory?
A new paper of interest this week:
McEwen GK, Goode DK, Parker HJ, Woolfe A, Callaway H, et al. (2009) Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates. PLoS Genet 5(12): e1000762. doi:10.1371/journal.pgen.1000762
Some general features of CNEs are well summarized by this paper on CNE (conserved non-coding elements). It says: “These elements (CNE) appear to be largely absent in invertebrates.” Another paper said: “(CNEs of invertebrates) are less frequent and are smaller in size than in vertebrates.”
Kimura, a founder of the neutral theory, said: “The neutral theory also asserts that most of the intraspecific variability at the molecular level (including protein and DNA polymorphism) is essentially neutral.” (1) It is interesting to note that this new paper managed to avoid the word ‘neutral theory’ completely, the theory most relevant in interpreting sequence similarity. This recent paper (2) is another one that managed doing that.
Most CNEs would be such sequences that differ between vertebrates and invertebrates and should therefore be neutral rather than functional if the neutral theory is correct. But since CNEs are functional, we have no choice here but to conclude that the neutral theory is incorrect. In fact, CNEs are just the latest evidence among many that deem the neutral theory correct only in the domain of microevolution or population genetics dealing with identical or very similar species.
From the neutral theory perspective, here is how it interprets genetic distance in a typical sequence such as cytochrome c. Human is closer to mouse than to chicken. But the closer distance between mouse and human is merely due to short time of divergence. If given ~245 more million years, human and mouse would have a distance similar to what is now observed between human and chicken. This interpretation by the neutral theory is of course the basis for all molecular trees inferred from genetic distances.
But this perspective cannot explain among many things the case regarding vertebrates and invertebrates. Both groups appeared at about the same time during the Cambrian explosion. So if time is the only variable for sequence diversity, conserved sequences found in one group should be similarly conserved in the other group. But this is clearly not the case. As your work and many others (2) show, sequences in vertebrates are more conserved than in invertebrates. For example, vertebrates have a largest observed distance of ~20 aa difference between lamprey and fish in cytochrome c. But within drosophila or insects it is ~30 aa difference.
To say that invertebrates evolve faster will not work because there are just too many pieces of evidence against that. For example, yeast is equidistant to drosophila and human in cytochrome c (36/102 aa difference). Such approximate equidistance holds for nearly all homologous genes among yeast, drosophila and humans (3).
The only sensible explanation to me that has no contradictions is to say that vertebrates are more complex than invertebrates and can tolerate far less random mutations. Many of the neutral sequences in invertebrates become non-neutral in vertebrates, and hence we have far more CNEs in vertebrates. The maximum number of neutral positions in invertebrates is higher than in vertebrates according to the Maximum Genetic Diversity hypothesis (4, 5). What are causing the conservation of CNEs in vertebrates? It is those extra functional constraints only found in vertebrates. More complexity demands more functions from a sequence. Complexity is well known to be not linked with absolute amount of sequences but is with how sequences are used (epigenetics). CNEs are epigenetic elements. There are more ways of using a given sequence in complex organisms, which puts extra constraints on the variability of the sequence.
Reference:
1. Kimura M. DNA and the neutral theory. Phil Trans R Soc Lond B 1986; 312:343-54.
2. Halabi N, Rivoire O, Leibler S, Ranganathan R. Protein sectors: evolutionary units of three-dimensional structure. Cell 2009; 138:774-86.
3. Huang S. The genetic equidistance result of molecular evolution is independent of mutation rates. J Comp Sci Syst Biol 2008; 1:092-102.
4. Huang S. Inverse relationship between genetic diversity and epigenetic complexity. Preprint available at Nature Precedings 2009;
5. Huang S. Histone methylation and the initiation of cancer, Cancer Epigenetics. New York: CRC Press, 2008.
McEwen GK, Goode DK, Parker HJ, Woolfe A, Callaway H, et al. (2009) Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates. PLoS Genet 5(12): e1000762. doi:10.1371/journal.pgen.1000762
Some general features of CNEs are well summarized by this paper on CNE (conserved non-coding elements). It says: “These elements (CNE) appear to be largely absent in invertebrates.” Another paper said: “(CNEs of invertebrates) are less frequent and are smaller in size than in vertebrates.”
Kimura, a founder of the neutral theory, said: “The neutral theory also asserts that most of the intraspecific variability at the molecular level (including protein and DNA polymorphism) is essentially neutral.” (1) It is interesting to note that this new paper managed to avoid the word ‘neutral theory’ completely, the theory most relevant in interpreting sequence similarity. This recent paper (2) is another one that managed doing that.
Most CNEs would be such sequences that differ between vertebrates and invertebrates and should therefore be neutral rather than functional if the neutral theory is correct. But since CNEs are functional, we have no choice here but to conclude that the neutral theory is incorrect. In fact, CNEs are just the latest evidence among many that deem the neutral theory correct only in the domain of microevolution or population genetics dealing with identical or very similar species.
From the neutral theory perspective, here is how it interprets genetic distance in a typical sequence such as cytochrome c. Human is closer to mouse than to chicken. But the closer distance between mouse and human is merely due to short time of divergence. If given ~245 more million years, human and mouse would have a distance similar to what is now observed between human and chicken. This interpretation by the neutral theory is of course the basis for all molecular trees inferred from genetic distances.
But this perspective cannot explain among many things the case regarding vertebrates and invertebrates. Both groups appeared at about the same time during the Cambrian explosion. So if time is the only variable for sequence diversity, conserved sequences found in one group should be similarly conserved in the other group. But this is clearly not the case. As your work and many others (2) show, sequences in vertebrates are more conserved than in invertebrates. For example, vertebrates have a largest observed distance of ~20 aa difference between lamprey and fish in cytochrome c. But within drosophila or insects it is ~30 aa difference.
To say that invertebrates evolve faster will not work because there are just too many pieces of evidence against that. For example, yeast is equidistant to drosophila and human in cytochrome c (36/102 aa difference). Such approximate equidistance holds for nearly all homologous genes among yeast, drosophila and humans (3).
The only sensible explanation to me that has no contradictions is to say that vertebrates are more complex than invertebrates and can tolerate far less random mutations. Many of the neutral sequences in invertebrates become non-neutral in vertebrates, and hence we have far more CNEs in vertebrates. The maximum number of neutral positions in invertebrates is higher than in vertebrates according to the Maximum Genetic Diversity hypothesis (4, 5). What are causing the conservation of CNEs in vertebrates? It is those extra functional constraints only found in vertebrates. More complexity demands more functions from a sequence. Complexity is well known to be not linked with absolute amount of sequences but is with how sequences are used (epigenetics). CNEs are epigenetic elements. There are more ways of using a given sequence in complex organisms, which puts extra constraints on the variability of the sequence.
Reference:
1. Kimura M. DNA and the neutral theory. Phil Trans R Soc Lond B 1986; 312:343-54.
2. Halabi N, Rivoire O, Leibler S, Ranganathan R. Protein sectors: evolutionary units of three-dimensional structure. Cell 2009; 138:774-86.
3. Huang S. The genetic equidistance result of molecular evolution is independent of mutation rates. J Comp Sci Syst Biol 2008; 1:092-102.
4. Huang S. Inverse relationship between genetic diversity and epigenetic complexity. Preprint available at Nature Precedings 2009;
5. Huang S. Histone methylation and the initiation of cancer, Cancer Epigenetics. New York: CRC Press, 2008.
Sunday, December 6, 2009
Building Complexity and the main pattern in evolution
Building complex and robust machine may have more ways than just one. To have backups or overlapping systems is one way of doing it, the most stupid and awkward way. Instead of a single engine in a small plane, a more complex large plane may have 4 engines with 2 of them as backups. But is that the nature’s way for using DNA to build complex life? Do we have an extra heart or brain or any organ as pure backups? We don’t. If we don’t do it at the phenotype level, do we do it at the genotype level? Mostly not. Our gene numbers are much smaller than any one had predicted because complexity is not linked to an increase in gene numbers or in back up genes. Nature is smarter and does it by combinations of genes and by inventing novel and complex ways of using the same set of genes. And by giving extra functions to an existing gene. We create music not by inventing more notes, and the ways of using the existing notes are already infinite.
To add back up or overlap system is not really an increase in complexity. A four engine plane and a one engine plane has the same level of complexity as far as the engine is concerned. To have a back up brain, we still need to have a complex brain in the first place. For that to happen, disorder and random mutation must be suppressed. Who can imagine a brain capable of infinite order like mathematics could tolerate a level of disorder/randomness in its building blocks like that of a flu virus or any simple virus like early life forms at the beginning of evolution?
The backup way is also not sound for DNA based lives because, in my thinking, it increases the size of the genome and hence the target size for mutations. The backup copy is not expressed or functional in normal situations and therefore not maintained by natural selection and can easily lose its function due to accumulation of mutations. Thus, it is safe to predict that most paralogs of a gene in a complex organism have unique functions and are not just backups (plenty of data for this). The claim of complex organisms have more backups is simply wishful thinking and not supported by facts. Don’t we have a lot of single mutation diseases in humans?
For both genotypes and phenotypes, nature follows the rule of use it or lose it. Backups may have been invented once but would simply be lost due to disuse. Which is more effective in advancing complexity: to decrease mutations or to use backups? All facts of nature say the first. It is simply a reality that a theory based on that notion explains all facts whereas any theory that ignores it meets with countless contradictions.
There is an extremely common mistake in the evolution field that has infected the lay public. It is to ignore the main pattern and use whatever trivial pattern/facts to suit our theory and to invalidate the main pattern when our theory does not predict it. Given the infinite amount of data/facts of nature, any stupid theory can find some factual support, if the goal is not to account for the major patterns or is not to explain all without contradiction. The advance with time in complexity is the dominant pattern in evolution that is so obvious that it is hardly worth stating. (The best ancient Chinese thinkers from 5000-7000 years ago had always placed man above all else in nature and as equal in status to the creative power of nature namely yang/heaven and yin/earth as written in I-ching, which has been the foundation for the most long lasting civilization as well as the world view of the largest population on Earth. Ancients have much better intuitive sense than moderns simply because their focus is less distracted by trivial things or man-made artifacts, and intuition is the foundation of science.) But since our theory does not predict that, we ignore it and cite trivial cases of randomness to support no direction towards complexity. Or we use trivial and much less common cases of complexity loss like loss of limbs in snakes as evidence for no direction towards higher complexity. Or we cite abundant cases of no change in complexity during microevolution. But all these merely indicate that in addition to complexity increase, there is also another trend for stability or no change. One cannot use a single mechanism to explain two opposite major trends, which is what we are doing.
We ignore the order/beauty/complexity of our big brain, and cite examples of imagined imperfections in some organs as evidence for the imperfections of nature or evolution. We ignore the general perfection of the human body and cite examples of rare diseases to fault the power of nature/evolution. In every case, the main pattern says that nature/evolution is all good, order, and beauty. The existence of disorder, randomness, and ugliness are all trivial and minor patterns. It is simply nonsensical to focus on the minor patterns and to turn blind to the main patterns. We should not explain the trivial at the expanse of the main but that has become a habitual behavior to most followers of evolution, another simple indication that we are not on the right path in understanding the main pattern.
To add back up or overlap system is not really an increase in complexity. A four engine plane and a one engine plane has the same level of complexity as far as the engine is concerned. To have a back up brain, we still need to have a complex brain in the first place. For that to happen, disorder and random mutation must be suppressed. Who can imagine a brain capable of infinite order like mathematics could tolerate a level of disorder/randomness in its building blocks like that of a flu virus or any simple virus like early life forms at the beginning of evolution?
The backup way is also not sound for DNA based lives because, in my thinking, it increases the size of the genome and hence the target size for mutations. The backup copy is not expressed or functional in normal situations and therefore not maintained by natural selection and can easily lose its function due to accumulation of mutations. Thus, it is safe to predict that most paralogs of a gene in a complex organism have unique functions and are not just backups (plenty of data for this). The claim of complex organisms have more backups is simply wishful thinking and not supported by facts. Don’t we have a lot of single mutation diseases in humans?
For both genotypes and phenotypes, nature follows the rule of use it or lose it. Backups may have been invented once but would simply be lost due to disuse. Which is more effective in advancing complexity: to decrease mutations or to use backups? All facts of nature say the first. It is simply a reality that a theory based on that notion explains all facts whereas any theory that ignores it meets with countless contradictions.
There is an extremely common mistake in the evolution field that has infected the lay public. It is to ignore the main pattern and use whatever trivial pattern/facts to suit our theory and to invalidate the main pattern when our theory does not predict it. Given the infinite amount of data/facts of nature, any stupid theory can find some factual support, if the goal is not to account for the major patterns or is not to explain all without contradiction. The advance with time in complexity is the dominant pattern in evolution that is so obvious that it is hardly worth stating. (The best ancient Chinese thinkers from 5000-7000 years ago had always placed man above all else in nature and as equal in status to the creative power of nature namely yang/heaven and yin/earth as written in I-ching, which has been the foundation for the most long lasting civilization as well as the world view of the largest population on Earth. Ancients have much better intuitive sense than moderns simply because their focus is less distracted by trivial things or man-made artifacts, and intuition is the foundation of science.) But since our theory does not predict that, we ignore it and cite trivial cases of randomness to support no direction towards complexity. Or we use trivial and much less common cases of complexity loss like loss of limbs in snakes as evidence for no direction towards higher complexity. Or we cite abundant cases of no change in complexity during microevolution. But all these merely indicate that in addition to complexity increase, there is also another trend for stability or no change. One cannot use a single mechanism to explain two opposite major trends, which is what we are doing.
We ignore the order/beauty/complexity of our big brain, and cite examples of imagined imperfections in some organs as evidence for the imperfections of nature or evolution. We ignore the general perfection of the human body and cite examples of rare diseases to fault the power of nature/evolution. In every case, the main pattern says that nature/evolution is all good, order, and beauty. The existence of disorder, randomness, and ugliness are all trivial and minor patterns. It is simply nonsensical to focus on the minor patterns and to turn blind to the main patterns. We should not explain the trivial at the expanse of the main but that has become a habitual behavior to most followers of evolution, another simple indication that we are not on the right path in understanding the main pattern.
Darwin's theory is coherent and hypothesis generating? Can a theory be proven true?
Stanley Sessions responded to my comments at Nature Precedings:http://precedings.nature.com/documents/2887/version/1#comments
"I think I understand at least some of what you are getting at…wonderful! I think of the schizoid pickle physics is in right now compared to biology, the latter thanks to the remarkable coherency of evolutionary theory. However, you get into some dangerous territory when you speak of scientific theories “proven to be true”. You can do that in math, but isn’t that why mathematics is usually stuck in Humanities with philosophy rather than in the Sciences? Finally, to me the Theory of Evolution (like any good theory) is a good theory not so much because of what it explains, but to the degree that it is useful in generating testable hypotheses."
my reply:
I am not surprised that you would consider the existing evolutionary theory remarkably coherent. It is common for lay people and scientists not in the field or all casual believers to take that view, and I myself was among them just a few years back. But any disinterested professional who is familiar with the details would think otherwise. The devil is in the details. For a true theory, the more details you know, the more you would marvel at its beauty. The opposite is true for a false theory. So, it does not bode well for any theory to claim a lot of lay admirers. “When told that only 3 men in the world understood Relativity, Sir Eddington asked "I wonder who is the third?" Lay people and non-specialist scientists have no business in judging a science theory one way or the other. Evolution theory should not be simpler than relativity or easier to grasp for lay people. After all, it is evolution that created the brain for understanding relativity. A science that is so simple that a lay person could feel like he knows all about it, as is commonly seen in forums on evolution, can hardly be called science. The 3000 year old book I-ching is the most mysterious book ever written and only a handful of people the like of Congzi can really claim some understanding of it, and yet that has not prevented it from being the very foundation for the world view of the largest population on Earth, most of whom have no first hand understanding of it.
A coherent theory should not lead 100% lay people and 99% biologists to have the wrong answer to a most basic question that has been extensively studied for nearly half a century. Which, frog or human, is closer to fish in sequence similarity in any given gene? And yet the other side of the same question can be answered correctly by nearly all people, thanks to 150 years of teaching Darwinism. Which, frog or fish, is closer to human in sequence similarity in any given gene? If you don’t believe me, try these two questions on your biology colleagues. Being a casual believer of Darwinism until a few years ago, I, a professional biologist with 25 years of research experience, answered incorrectly a few years ago and found the right answer the hard way, by reinventing the wheel (no specialist has offered it in any books for the non-specialists and what is being offered can only mislead). That was truly a shocking experience and a big reason for me to get into studying evolution or to try to solve the puzzle myself given that few cared to do it. I have done enough to realize there is a big hole in our present state of affairs. The seeming coherency is a huge bubble. The fact that one must use Darwinism for phenotypes and the negation of it (neutral theory) for genotypes, despite the inseparable unity of genotypes and phenotypes, would easily strike any biology student as odd and incoherent.
The only reason that specialists seem to have a consensus view in public is because they have all agreed that contradictions are no big deal and that they can never be certain about anything in evolution, more for serve-serving than for the love of science/truth. They of course know it is a big deal in their private moment, as is apparent from the fact that you rarely see them teach the contradicting details to the non-specialists in books such as Why Evolution Is True. (While another person may easily read this as a conspiracy, I would just view it as simple human nature) One of the results of their selective teaching is that nearly all people know the answer to one side of a question while nearly no one knows the other side of the same question as mentioned above. In contrast, physicists, more of a hard core scientist, will not easily settle for any theory with contradictions, and hence no consensus yet on the cutting edge physics as you have correctly observed. But that is healthy for science and is what science is all about. Evolution research could for its own great benefit really use some challenge to the paradigm, especially a voice asking for a contradiction free theory and for not stretching a contradiction free theory of microevolution to where it meets contradictions and hence does not belong. No truth is afraid of a competitor because there can only be room for one truth, and there is no possibility of two theories explaining nature equally well.
My point is mostly about proving a theory wrong. It is debatable whether a theory cannot ever be proven true (see below). But it is often overlooked by biologists that a single contradiction/exception should prove a theory wrong. Your point about generating testable hypothesis is absolutely essential. But that is really a minimum, and meeting that standard is not enough. The theory must also be prepared to accept all the consequences of the test, one of which is to kill the theory or at least narrow its domain of relevance. If the theory stands regardless of the test results, then it is not a scientific theory. Unfortunately, the modern evolution theory is like that. I have personally found and published exceptions/contradictions to the theory and few cared. And many others have of course experienced the same. Few textbooks ever highlight those contradictions. And yet a sharp reader can still infer from what is not said. What he does not read anywhere is a statement by a reputed evolutionist that the modern evolution theory has no contradictions. But I do not waste energy to complain and I am fully aware just like any good scientists that a theory is never overthrown by contradictions but must be pushed away by an alternative better theory. Scientists who overlook those contradictions do it at their own peril as they are wasting their careers by barking up the wrong tree. There will always be people though in small number who will pay attention to those contradictions and try to do something about them and hence have a chance to make history.
For theory testing to be meaningful, the standard of no single contradiction is essential. If you allow contradictions, why bother testing in the first place? No doubt the modern evolution theory has been tested true or generated testable hypotheses but of course only in microevolution (e.g., Lenski’s and Grants’ experiments on bacteria and finches). It is equally clear that it is largely irrelevant to macroevolution if we use the same standard as we use for claiming it true for microevolution. All the contradictions are in macroevolution and none in microevolution.
A theory that has not even explained all known relevant facts is not even worth testing because it is already false. It has already allowed exceptions, which makes testing meaningless. To explain all existing relevant facts is therefore a minimum for any theory to qualify to be tested. And if a theory has explained all relevant facts, it would be impossible for it not to be able to generate testable hypotheses that would just confirm it further. Explaining a fact is the same as predicting it when a theory is axiom based rather than induced from factual observations. If a theory is induced from 10 known facts, then none of these 10 can serve as evidence for it (to do so is a tautology) and further testing is necessary. In contrast, if a theory is deduced from an axiom, then it is self evidently true and can exist independent of any facts and can rightfully claim all facts as evidence if it deduces/predicts/explains all of them.
I here provide a simple rationale for why a theory that has explained all known key facts without a single contradiction must be true or has been proven true. We first grant that for any domain of nature there is only one unique true theory or law that explains or governs it. This is at least 100% true for all the known laws of nature. If a theory has explained all key facts without contradiction, it is effectively indistinguishable from an ideal true law. Since there cannot be two true laws or more than one true law for any single domain, any theory that explains all key facts is effectively the true law. What are key facts? A key fact is any representative of a key class of facts that have the same fundamental feature. The knowledge of today cannot possibly have all the facts of a class known, which may be infinite. But it is not unrealistic for today’s knowledge to include at least one fact out of every major key class of facts of certain domains. And explaining one such representative of a key class is of course equivalent to explaining that whole class. In most cases, to explain all the known key classes in a coherent fashion (while granting the existence of some unknown key classes) is simply impossible unless one has the true law, given that all facts are connected by a single law and cannot possibly be connected by any laws other than the single unique true law.
Have Newton’s laws of motion been tested by all possible tests? Of course not, impossible to do. Are they proven laws? Of course they are because they explained every key fact known even if we grant there are unknown key facts and tested true in every test within their domain of relevance. It is also important that they are axiom based or self-evidently true, which means that their truthfulness is only a matter of how general or broad of their domain of relevance rather than having a possibility of being not true at all in any domain. Are they also wrong? Yes, outside of their domain of relevance.
The nearly half century old genetic equidistance result of Margoliash for cytochrome c is a key fact that is representative of most genes of most species. It is the answer to the above simple question on frog/fish that almost all people fail. How this single fact is interpreted determines how modern evolution research is to proceed and how half of the record of evolution (the DNA half vs the other half fossils/phenotypes) is to be interpreted. Its incorrect and tautological interpretation, the molecular clock and the neutral theory, has misled the field of evolution for nearly half a century with grave consequences. For one, no non-specialists know much about it and the less they know it, the more coherent they view Darwinism, which suits the Darwin specialists just fine. Some actual data for this. The wiki page on Motoo Kimura has a pathetic ~1500 views compared to Darwin with ~260, 000 views a month, never mind that it is Kimura’s theory rather than Darwin’s that is most relevant to modern evolution research on DNAs in the past half century. Also, the page on the neutral theory has 3000 while natural selection has 90,000 views a month.
The other grave consequence is to misidentify chimpanzee as our closest blood relative among non-humans in total violation of the fossil record and common sense. Another is to give us endless conflicting interpretations on the phylogenetic position of some species such as tarsiers. A set of conflicting interpretations must contain a false one. Any theory that can turn perfectly solid DNA data into a false interpretation of reality can only be incorrect, regardless whether it sometimes can also produce a correct interpretation by accident. Any theory that has turned DNA data into conflicting interpretations of the reality of phylogeny has of course self-proven itself false.
The fact that Darwin’s theory can coexist in peace with such a false theory of molecular evolution in a form termed the modern evolution theory does not bode well for it. All these theories are from the beginning based on population genetics and should have just stayed where they really belong, microevolution and population genetics. As far as I am concerned, no theory of any kind, except the maximum genetic diversity hypothesis, has correctly explained the equidistance result and thus has any chance of being true for the whole domain of evolution or has even qualified as worth further testing.
"I think I understand at least some of what you are getting at…wonderful! I think of the schizoid pickle physics is in right now compared to biology, the latter thanks to the remarkable coherency of evolutionary theory. However, you get into some dangerous territory when you speak of scientific theories “proven to be true”. You can do that in math, but isn’t that why mathematics is usually stuck in Humanities with philosophy rather than in the Sciences? Finally, to me the Theory of Evolution (like any good theory) is a good theory not so much because of what it explains, but to the degree that it is useful in generating testable hypotheses."
my reply:
I am not surprised that you would consider the existing evolutionary theory remarkably coherent. It is common for lay people and scientists not in the field or all casual believers to take that view, and I myself was among them just a few years back. But any disinterested professional who is familiar with the details would think otherwise. The devil is in the details. For a true theory, the more details you know, the more you would marvel at its beauty. The opposite is true for a false theory. So, it does not bode well for any theory to claim a lot of lay admirers. “When told that only 3 men in the world understood Relativity, Sir Eddington asked "I wonder who is the third?" Lay people and non-specialist scientists have no business in judging a science theory one way or the other. Evolution theory should not be simpler than relativity or easier to grasp for lay people. After all, it is evolution that created the brain for understanding relativity. A science that is so simple that a lay person could feel like he knows all about it, as is commonly seen in forums on evolution, can hardly be called science. The 3000 year old book I-ching is the most mysterious book ever written and only a handful of people the like of Congzi can really claim some understanding of it, and yet that has not prevented it from being the very foundation for the world view of the largest population on Earth, most of whom have no first hand understanding of it.
A coherent theory should not lead 100% lay people and 99% biologists to have the wrong answer to a most basic question that has been extensively studied for nearly half a century. Which, frog or human, is closer to fish in sequence similarity in any given gene? And yet the other side of the same question can be answered correctly by nearly all people, thanks to 150 years of teaching Darwinism. Which, frog or fish, is closer to human in sequence similarity in any given gene? If you don’t believe me, try these two questions on your biology colleagues. Being a casual believer of Darwinism until a few years ago, I, a professional biologist with 25 years of research experience, answered incorrectly a few years ago and found the right answer the hard way, by reinventing the wheel (no specialist has offered it in any books for the non-specialists and what is being offered can only mislead). That was truly a shocking experience and a big reason for me to get into studying evolution or to try to solve the puzzle myself given that few cared to do it. I have done enough to realize there is a big hole in our present state of affairs. The seeming coherency is a huge bubble. The fact that one must use Darwinism for phenotypes and the negation of it (neutral theory) for genotypes, despite the inseparable unity of genotypes and phenotypes, would easily strike any biology student as odd and incoherent.
The only reason that specialists seem to have a consensus view in public is because they have all agreed that contradictions are no big deal and that they can never be certain about anything in evolution, more for serve-serving than for the love of science/truth. They of course know it is a big deal in their private moment, as is apparent from the fact that you rarely see them teach the contradicting details to the non-specialists in books such as Why Evolution Is True. (While another person may easily read this as a conspiracy, I would just view it as simple human nature) One of the results of their selective teaching is that nearly all people know the answer to one side of a question while nearly no one knows the other side of the same question as mentioned above. In contrast, physicists, more of a hard core scientist, will not easily settle for any theory with contradictions, and hence no consensus yet on the cutting edge physics as you have correctly observed. But that is healthy for science and is what science is all about. Evolution research could for its own great benefit really use some challenge to the paradigm, especially a voice asking for a contradiction free theory and for not stretching a contradiction free theory of microevolution to where it meets contradictions and hence does not belong. No truth is afraid of a competitor because there can only be room for one truth, and there is no possibility of two theories explaining nature equally well.
My point is mostly about proving a theory wrong. It is debatable whether a theory cannot ever be proven true (see below). But it is often overlooked by biologists that a single contradiction/exception should prove a theory wrong. Your point about generating testable hypothesis is absolutely essential. But that is really a minimum, and meeting that standard is not enough. The theory must also be prepared to accept all the consequences of the test, one of which is to kill the theory or at least narrow its domain of relevance. If the theory stands regardless of the test results, then it is not a scientific theory. Unfortunately, the modern evolution theory is like that. I have personally found and published exceptions/contradictions to the theory and few cared. And many others have of course experienced the same. Few textbooks ever highlight those contradictions. And yet a sharp reader can still infer from what is not said. What he does not read anywhere is a statement by a reputed evolutionist that the modern evolution theory has no contradictions. But I do not waste energy to complain and I am fully aware just like any good scientists that a theory is never overthrown by contradictions but must be pushed away by an alternative better theory. Scientists who overlook those contradictions do it at their own peril as they are wasting their careers by barking up the wrong tree. There will always be people though in small number who will pay attention to those contradictions and try to do something about them and hence have a chance to make history.
For theory testing to be meaningful, the standard of no single contradiction is essential. If you allow contradictions, why bother testing in the first place? No doubt the modern evolution theory has been tested true or generated testable hypotheses but of course only in microevolution (e.g., Lenski’s and Grants’ experiments on bacteria and finches). It is equally clear that it is largely irrelevant to macroevolution if we use the same standard as we use for claiming it true for microevolution. All the contradictions are in macroevolution and none in microevolution.
A theory that has not even explained all known relevant facts is not even worth testing because it is already false. It has already allowed exceptions, which makes testing meaningless. To explain all existing relevant facts is therefore a minimum for any theory to qualify to be tested. And if a theory has explained all relevant facts, it would be impossible for it not to be able to generate testable hypotheses that would just confirm it further. Explaining a fact is the same as predicting it when a theory is axiom based rather than induced from factual observations. If a theory is induced from 10 known facts, then none of these 10 can serve as evidence for it (to do so is a tautology) and further testing is necessary. In contrast, if a theory is deduced from an axiom, then it is self evidently true and can exist independent of any facts and can rightfully claim all facts as evidence if it deduces/predicts/explains all of them.
I here provide a simple rationale for why a theory that has explained all known key facts without a single contradiction must be true or has been proven true. We first grant that for any domain of nature there is only one unique true theory or law that explains or governs it. This is at least 100% true for all the known laws of nature. If a theory has explained all key facts without contradiction, it is effectively indistinguishable from an ideal true law. Since there cannot be two true laws or more than one true law for any single domain, any theory that explains all key facts is effectively the true law. What are key facts? A key fact is any representative of a key class of facts that have the same fundamental feature. The knowledge of today cannot possibly have all the facts of a class known, which may be infinite. But it is not unrealistic for today’s knowledge to include at least one fact out of every major key class of facts of certain domains. And explaining one such representative of a key class is of course equivalent to explaining that whole class. In most cases, to explain all the known key classes in a coherent fashion (while granting the existence of some unknown key classes) is simply impossible unless one has the true law, given that all facts are connected by a single law and cannot possibly be connected by any laws other than the single unique true law.
Have Newton’s laws of motion been tested by all possible tests? Of course not, impossible to do. Are they proven laws? Of course they are because they explained every key fact known even if we grant there are unknown key facts and tested true in every test within their domain of relevance. It is also important that they are axiom based or self-evidently true, which means that their truthfulness is only a matter of how general or broad of their domain of relevance rather than having a possibility of being not true at all in any domain. Are they also wrong? Yes, outside of their domain of relevance.
The nearly half century old genetic equidistance result of Margoliash for cytochrome c is a key fact that is representative of most genes of most species. It is the answer to the above simple question on frog/fish that almost all people fail. How this single fact is interpreted determines how modern evolution research is to proceed and how half of the record of evolution (the DNA half vs the other half fossils/phenotypes) is to be interpreted. Its incorrect and tautological interpretation, the molecular clock and the neutral theory, has misled the field of evolution for nearly half a century with grave consequences. For one, no non-specialists know much about it and the less they know it, the more coherent they view Darwinism, which suits the Darwin specialists just fine. Some actual data for this. The wiki page on Motoo Kimura has a pathetic ~1500 views compared to Darwin with ~260, 000 views a month, never mind that it is Kimura’s theory rather than Darwin’s that is most relevant to modern evolution research on DNAs in the past half century. Also, the page on the neutral theory has 3000 while natural selection has 90,000 views a month.
The other grave consequence is to misidentify chimpanzee as our closest blood relative among non-humans in total violation of the fossil record and common sense. Another is to give us endless conflicting interpretations on the phylogenetic position of some species such as tarsiers. A set of conflicting interpretations must contain a false one. Any theory that can turn perfectly solid DNA data into a false interpretation of reality can only be incorrect, regardless whether it sometimes can also produce a correct interpretation by accident. Any theory that has turned DNA data into conflicting interpretations of the reality of phylogeny has of course self-proven itself false.
The fact that Darwin’s theory can coexist in peace with such a false theory of molecular evolution in a form termed the modern evolution theory does not bode well for it. All these theories are from the beginning based on population genetics and should have just stayed where they really belong, microevolution and population genetics. As far as I am concerned, no theory of any kind, except the maximum genetic diversity hypothesis, has correctly explained the equidistance result and thus has any chance of being true for the whole domain of evolution or has even qualified as worth further testing.
Tuesday, November 24, 2009
On the standard for truth and the role of communication in disseminating scientific ideas
Someone wrote an article on the talent of Darwin in amassing support for and in communicating the idea of Darwinism.
Sessions, Stanley and Macgregor, Herbert. (2009) The Necessity of Darwin. Available from Nature Precedings, http://hdl.handle.net/10101/npre.2009.2887.1
I responded by saying that ideas are more important than amassing facts and communication. And I got a counter response that ideas are cheap and communication is key. I responded with the following:
You have some good points but you overlooked the fact that the opposite of your points are also true. Like all fundamental things in nature, seldom is a thing true without its opposite also true. I am referring in my earlier message one kind of idea, the greatest ones, since we are talking about Darwin and Mendel, whereas you are referring to another kind, good or average ones. I here argue that we are both correct.
You are right in the sense that an idea must explain detailed facts for it to be a scientific rather than a philosophical one. I am thinking the countless non-mainstream theories of evolution that one can easily discard for one simple reason, they explain few details and are just general empty claims. No question that Darwin is singly important in making the idea of natural selection a scientific theory. But I would like to point out here, as it is commonly overlooked by biologists, that amassing a lot of support data is not the same as proving the idea right. While it is very important to amass data to support an idea, a quantitative difference in amount of data is less critical if no one has explained all relevant facts without contradiction. So long the idea is not completely true, to amass 99% of all relevant facts to support it is only slightly or quantitatively better than to amass 1%. A true idea only cares about 100%. Darwin clearly did not explain all relevant facts as he had a chapter in his book on the difficulties with his theory. Faced with such difficulties, another person would easily either bury his idea or narrow the domain of relevance for his idea.
An idea that explains 99% of all relevant facts is only slightly or quantitatively better than another idea that explains 1%. But they are all qualitatively the same: they are all false or at least incomplete. So long an idea does not explain 100% of all relevant facts or has one single exception within its domain of relevance, it is not a completely true idea. The difference between truth and falsehood is not quantitative but qualitative. The idea that the standard of true idea should be without a single contradiction is from priori reason and universally adopted by mathematicians. But it is presently unpopular among evolution biologists or biologists in general. So it is worthwhile here to explain why we have no other choice but to use that standard. (a single contradiction is really equivalent infinite number of contradiction. Once you allow one, you can of course allow 2, and in turn 3, 4, … all the way to infinity. Nature’s phenomena are unlimited and a theory with a single contradiction today could easily meet a few hundred in a few generations)
Let’s grant that nature is a coherent whole governed by laws, which we must since that is the reason for science to be possible. Let’s say there are 100 independent phenomena in nature. Law 1 explains 99 of them but left one out because it is a contradiction. So we have law 2 to explain the single contradiction. If law 2 happens to contradict or negate law 1, which could happen since the phenomenon explained by law 2 contradicts law 1 (in real world, we have the neutral theory negating Darwinism), which one then is the correct law? This may have two possible solutions. One is to say that neither is correct and we can then back that up by finding a true law that takes care of all 100 phenomena. This is why I said 99% is not much better than 1%. You may ask how can a wrong law explain 99%? Easy, by chance and mistaken explanation. E.g, the molecular clock or neutral theory has been used to explain close to 99% of all macro-evo phenomena and no one would consider it possible for those explanations to be all false although every one knows the theory has contradictions. But at least to me at this point in time, the new maximum genetic diversity (MGD) hypothesis has made it blatantly clear that all the data can be totally reinterpreted in a different and much better way or contradiction free way. The molecular clock should never have been invented in the first place. And if people had used the standard of no single contradiction, we could have easily prevented the contradiction-laden clock/neutral theory to last for nearly half a century. Since I have offered the MGD as an easy target to shoot down (just one contradicting detail is enough), I am not the kind of people who applies high standard only to others. And the MGD should prevent people from taking the easy excuse that biology or evolution is special or should be made an exception to the standard of no single contradiction.
The second way is to say that both laws are correct but just applies in different domains of relevance. So here each law has in fact explained everything in its domain of relevance in a contradiction-free manner. Now this does not contradict the idea that there should be only one universal law. All one needs to do is to combine the two opposite laws as two different aspects of a single universal law. Thus, Darwinism explained a lot of things but failed a lot too. One can either say it is completely wrong as an idea for the whole domain of evolution (here a single contradiction is sufficient to justify that saying) or one can say it is completely true within its domain of relevance (microevolution). Thus, the MGD includes Darwinism as a largely true account of microevo and can in turn claim to be a 100% correct theory for the whole domain of evolution, at least before a single contradiction to show up to ruin it.
In this day and era, an idea is seldom completely wrong but a common mistake of people is to apply the idea out of its proper domain of relevance. The standard of 100% contradiction-free is absolutely necessary as it is the only way to know whether a theory is completely true within its domain of relevance. It is the only way we can have multiple 100% correct laws of nature with each taking care of a small domain. We should never value a law that explains 99% as better than another one that explains the remaining 1%. Those two laws are either both false (as a general law for the whole domain) or both correct (as a narrow law for a smaller domain of relevance). A law is either 100% correct or false. There is no such thing as a 99% correct law!!
When we do find ourselves faced with a 99% correct law, we should first see if we can narrow the domain of relevance and hence make the law 100% correct in a smaller domain. If we cannot do that, then we have no choice but to search for a replacement that is 100% correct. The coherence of nature guarantees that we will find if we try. Nature is such that it would take a miracle to find a contradiction to its law if man has accurately stated that law. In contrast, it would take no effort to find a contradiction to a falsely formulated man-made law. The fact that no biological laws or patterns have been found to be 100% correct simply means we are searching for patterns in the wrong place where a pattern is not supposed to be there in the first place. The molecular clock, neutral theory, and Darwin’s theory all have great virtues for their respective specific domain of relevance where they are 100% correct. It is only when we force these domain specific theories upon some areas of nature where they don’t belong that we observe contradictions.
So, an important job for any theorists is to know where your theory does not belong. The only way to know this is to stick to the standard of 100% contradiction free. The worst theory possible is a tautological interpretation of a single phenomenon that has in its domain of relevance only one single phenomenon. The greatest theory is of course one that includes all phenomena of nature within its domain of relevance. Between the two, we have countless domain specific theories that are all 100% contradiction free within their respective domain but will of course meet contradictions and hence are false once they step outside of their bounds.
Now back to ideas and communication. A great idea speaks for itself and its best friend is time rather than communication. Good communication of course will not hurt. But in reality it could help little. A great idea is great often because it is destructive to an existing paradigm. The paradigm will resist change to protect its self-interest, often for personal and practical reasons like jobs and grants, which is totally understandable and should not be criticized too much as no one is superhuman and a paradigm is almost never completely wrong in the modern science era. Planck is very sharp in famously saying that a revolutionary idea never converts the old but just waits for them to die and for the new generation to take it up. Thus, communication is often irrelevant to great ideas. People can always choose and have always chosen to refuse to be talked into if they know the acceptance of the new could only hurt them personally.
Regardless of what you say about Darwin’s talent in communication, he will be judged by time on how true his idea is. If his idea is true and great, the past 150 years of history would only serve to invalidate your point about his talent in communication. But I fully share the notion that Darwin’s contribution is singly critical in making evolution a branch of science and a household concept. Science has generally benefited greatly from his effort in advancing the idea like no one else in his time.
Poor communication can only ruin a cheap/average idea but it can do little real damage because we can always have 5 or more people to hit upon the same idea in a short span of time. The idea of natural selection was independently invented 5 times in a short span of 40 years, by Wells, Blyth, Matthew, Darwin, and Wallace. But I do see that Darwin was unique among the five in seeing and advancing the unlimited potential for natural selection that clearly Blyth did not see or refused to see. But I think that the jury is still out whose version of natural selection will prove to be correct. All the data of experimental evolution in the past have proven neither wrong for microevolution but are anyway only capable of resolving issues of microevolution.
This brings up a novel perspective to view just how impossible for the idea of these 5 inventors of natural selection to turn out to be completely true. With a total ignorance of the molecular mechanisms of heredity, i.e., genetics and epigenetics, it would have to easily qualify as a miracle for any single human being to invent an idea of evolution that could explain every key detail of evolution from phenotypes down to molecules. (it would be a miracle for even a geneticist to invent a true idea of evolution if he is totally ignorant of epigenetics) Now imagine such a miracle not only has to happen once but 5 times in a short span of 40 years. Well, miracle never happens in nature as far as I am concerned or science is concerned. The natural way of advancing science is for ideas to come in accordance with knowledge/data collection. If epigenetics is a part of evolution (there is no doubt it should be even if based on pure priori reason alone), the natural and non-miraculous timing for the birth of a complete theory is of course today when epigenetics is finally at the cutting edge of advancing biology. Unless of course there is a third way of heredity to be discovered in the future (highly unlikely), history will no doubt remember today as the best and only time in human history that human could realistically come to a true understanding of evolution.
Sessions, Stanley and Macgregor, Herbert. (2009) The Necessity of Darwin. Available from Nature Precedings, http://hdl.handle.net/10101/npre.2009.2887.1
I responded by saying that ideas are more important than amassing facts and communication. And I got a counter response that ideas are cheap and communication is key. I responded with the following:
You have some good points but you overlooked the fact that the opposite of your points are also true. Like all fundamental things in nature, seldom is a thing true without its opposite also true. I am referring in my earlier message one kind of idea, the greatest ones, since we are talking about Darwin and Mendel, whereas you are referring to another kind, good or average ones. I here argue that we are both correct.
You are right in the sense that an idea must explain detailed facts for it to be a scientific rather than a philosophical one. I am thinking the countless non-mainstream theories of evolution that one can easily discard for one simple reason, they explain few details and are just general empty claims. No question that Darwin is singly important in making the idea of natural selection a scientific theory. But I would like to point out here, as it is commonly overlooked by biologists, that amassing a lot of support data is not the same as proving the idea right. While it is very important to amass data to support an idea, a quantitative difference in amount of data is less critical if no one has explained all relevant facts without contradiction. So long the idea is not completely true, to amass 99% of all relevant facts to support it is only slightly or quantitatively better than to amass 1%. A true idea only cares about 100%. Darwin clearly did not explain all relevant facts as he had a chapter in his book on the difficulties with his theory. Faced with such difficulties, another person would easily either bury his idea or narrow the domain of relevance for his idea.
An idea that explains 99% of all relevant facts is only slightly or quantitatively better than another idea that explains 1%. But they are all qualitatively the same: they are all false or at least incomplete. So long an idea does not explain 100% of all relevant facts or has one single exception within its domain of relevance, it is not a completely true idea. The difference between truth and falsehood is not quantitative but qualitative. The idea that the standard of true idea should be without a single contradiction is from priori reason and universally adopted by mathematicians. But it is presently unpopular among evolution biologists or biologists in general. So it is worthwhile here to explain why we have no other choice but to use that standard. (a single contradiction is really equivalent infinite number of contradiction. Once you allow one, you can of course allow 2, and in turn 3, 4, … all the way to infinity. Nature’s phenomena are unlimited and a theory with a single contradiction today could easily meet a few hundred in a few generations)
Let’s grant that nature is a coherent whole governed by laws, which we must since that is the reason for science to be possible. Let’s say there are 100 independent phenomena in nature. Law 1 explains 99 of them but left one out because it is a contradiction. So we have law 2 to explain the single contradiction. If law 2 happens to contradict or negate law 1, which could happen since the phenomenon explained by law 2 contradicts law 1 (in real world, we have the neutral theory negating Darwinism), which one then is the correct law? This may have two possible solutions. One is to say that neither is correct and we can then back that up by finding a true law that takes care of all 100 phenomena. This is why I said 99% is not much better than 1%. You may ask how can a wrong law explain 99%? Easy, by chance and mistaken explanation. E.g, the molecular clock or neutral theory has been used to explain close to 99% of all macro-evo phenomena and no one would consider it possible for those explanations to be all false although every one knows the theory has contradictions. But at least to me at this point in time, the new maximum genetic diversity (MGD) hypothesis has made it blatantly clear that all the data can be totally reinterpreted in a different and much better way or contradiction free way. The molecular clock should never have been invented in the first place. And if people had used the standard of no single contradiction, we could have easily prevented the contradiction-laden clock/neutral theory to last for nearly half a century. Since I have offered the MGD as an easy target to shoot down (just one contradicting detail is enough), I am not the kind of people who applies high standard only to others. And the MGD should prevent people from taking the easy excuse that biology or evolution is special or should be made an exception to the standard of no single contradiction.
The second way is to say that both laws are correct but just applies in different domains of relevance. So here each law has in fact explained everything in its domain of relevance in a contradiction-free manner. Now this does not contradict the idea that there should be only one universal law. All one needs to do is to combine the two opposite laws as two different aspects of a single universal law. Thus, Darwinism explained a lot of things but failed a lot too. One can either say it is completely wrong as an idea for the whole domain of evolution (here a single contradiction is sufficient to justify that saying) or one can say it is completely true within its domain of relevance (microevolution). Thus, the MGD includes Darwinism as a largely true account of microevo and can in turn claim to be a 100% correct theory for the whole domain of evolution, at least before a single contradiction to show up to ruin it.
In this day and era, an idea is seldom completely wrong but a common mistake of people is to apply the idea out of its proper domain of relevance. The standard of 100% contradiction-free is absolutely necessary as it is the only way to know whether a theory is completely true within its domain of relevance. It is the only way we can have multiple 100% correct laws of nature with each taking care of a small domain. We should never value a law that explains 99% as better than another one that explains the remaining 1%. Those two laws are either both false (as a general law for the whole domain) or both correct (as a narrow law for a smaller domain of relevance). A law is either 100% correct or false. There is no such thing as a 99% correct law!!
When we do find ourselves faced with a 99% correct law, we should first see if we can narrow the domain of relevance and hence make the law 100% correct in a smaller domain. If we cannot do that, then we have no choice but to search for a replacement that is 100% correct. The coherence of nature guarantees that we will find if we try. Nature is such that it would take a miracle to find a contradiction to its law if man has accurately stated that law. In contrast, it would take no effort to find a contradiction to a falsely formulated man-made law. The fact that no biological laws or patterns have been found to be 100% correct simply means we are searching for patterns in the wrong place where a pattern is not supposed to be there in the first place. The molecular clock, neutral theory, and Darwin’s theory all have great virtues for their respective specific domain of relevance where they are 100% correct. It is only when we force these domain specific theories upon some areas of nature where they don’t belong that we observe contradictions.
So, an important job for any theorists is to know where your theory does not belong. The only way to know this is to stick to the standard of 100% contradiction free. The worst theory possible is a tautological interpretation of a single phenomenon that has in its domain of relevance only one single phenomenon. The greatest theory is of course one that includes all phenomena of nature within its domain of relevance. Between the two, we have countless domain specific theories that are all 100% contradiction free within their respective domain but will of course meet contradictions and hence are false once they step outside of their bounds.
Now back to ideas and communication. A great idea speaks for itself and its best friend is time rather than communication. Good communication of course will not hurt. But in reality it could help little. A great idea is great often because it is destructive to an existing paradigm. The paradigm will resist change to protect its self-interest, often for personal and practical reasons like jobs and grants, which is totally understandable and should not be criticized too much as no one is superhuman and a paradigm is almost never completely wrong in the modern science era. Planck is very sharp in famously saying that a revolutionary idea never converts the old but just waits for them to die and for the new generation to take it up. Thus, communication is often irrelevant to great ideas. People can always choose and have always chosen to refuse to be talked into if they know the acceptance of the new could only hurt them personally.
Regardless of what you say about Darwin’s talent in communication, he will be judged by time on how true his idea is. If his idea is true and great, the past 150 years of history would only serve to invalidate your point about his talent in communication. But I fully share the notion that Darwin’s contribution is singly critical in making evolution a branch of science and a household concept. Science has generally benefited greatly from his effort in advancing the idea like no one else in his time.
Poor communication can only ruin a cheap/average idea but it can do little real damage because we can always have 5 or more people to hit upon the same idea in a short span of time. The idea of natural selection was independently invented 5 times in a short span of 40 years, by Wells, Blyth, Matthew, Darwin, and Wallace. But I do see that Darwin was unique among the five in seeing and advancing the unlimited potential for natural selection that clearly Blyth did not see or refused to see. But I think that the jury is still out whose version of natural selection will prove to be correct. All the data of experimental evolution in the past have proven neither wrong for microevolution but are anyway only capable of resolving issues of microevolution.
This brings up a novel perspective to view just how impossible for the idea of these 5 inventors of natural selection to turn out to be completely true. With a total ignorance of the molecular mechanisms of heredity, i.e., genetics and epigenetics, it would have to easily qualify as a miracle for any single human being to invent an idea of evolution that could explain every key detail of evolution from phenotypes down to molecules. (it would be a miracle for even a geneticist to invent a true idea of evolution if he is totally ignorant of epigenetics) Now imagine such a miracle not only has to happen once but 5 times in a short span of 40 years. Well, miracle never happens in nature as far as I am concerned or science is concerned. The natural way of advancing science is for ideas to come in accordance with knowledge/data collection. If epigenetics is a part of evolution (there is no doubt it should be even if based on pure priori reason alone), the natural and non-miraculous timing for the birth of a complete theory is of course today when epigenetics is finally at the cutting edge of advancing biology. Unless of course there is a third way of heredity to be discovered in the future (highly unlikely), history will no doubt remember today as the best and only time in human history that human could realistically come to a true understanding of evolution.
Friday, November 13, 2009
Real reason for the endless production of conflicting results on tarsiers
A couple of weeks ago, a new paper by Chatterjee et al. appeared on primate phylogeny that groups tarsiers with prosimians.
“Estimating the phylogeny and divergence times of primates using a supermatrix approach” Helen J Chatterjee, Simon YW Ho, Ian Barnes, and Colin Groves
BMC Evolutionary Biology 2009, 9:259 doi:10.1186/1471-2148-9-259
I sent the following comment titled “Real reason for the endless production of conflicting results on tarsiers” to the Journal’s website:
On the position of tarsiers, Chatterjee et al wrote: “The majority of molecular evidence supports the latter grouping [4,10-13] (grouping tarsiers with higher primates), although a large number of molecular studies still provide support for the Prosimii concept [14-18].”
When a method or technique can lead to two opposite results repeatedly and seemingly endlessly while only one of the two can be true, it is time to ask whether something is fundamentally missing with our method (all existing popular methods are slightly different from one another but are fundamentally the same kind). Let us start from the very beginning and examine the assumptions for our method. The key assumption for all sequence similarity based methods is that sequence dissimilarity always correlates with time of divergence. Well, is this true? We don’t have to be a specialist to know that this is sometimes true and sometimes not. Thus, for our method to be able to produce accurate and uncertainty-free result, it must take into account the reality that sequence dissimilarity sometimes does not correlate with time of divergence. Many of the sequence comparisons are not informative and should and must be excluded from our method. When they are not as is the case with all existing methods, they contribute to the high noise level that can sometimes overwhelm the signal. It is by accident that these methods sometimes give correct results and sometimes wrong results and no one knows why the difference or when to view such a result correct and final. Therefore, we have a peculiar non-scientific situation: no one is taking anyone else’s results as the final say. Never mind that we only have one true phylogeny of life on Earth. Once you know it, it is done and no more work needed. The existing methods are perfect for keeping some of us employed forever but will never give us truth. Truth is not judged by a quantitative difference in the number of studies that support it versus those against it. The correct method should produce zero number of studies that is against truth or should be immune to the production of conflicting results.
Data + method = result. The data here in molecular phylogeny is just sequence facts and cannot possibly be wrong so long one is not making sequencing errors. Thus the only way to produce a false result or conflicting results in phylogeny is through an incorrect method. Since all existing methods are perfectly capable of producing false results and have all in practice produced false results or conflicting results, it is another simple proof that the existing popular methods are simply incorrect.
By the own admission of the leading experts, the existing popular methods are flawed in the sense that they can easily produce incorrect results that are totally out of the hands of the scientists:
“Unlike the case in physics, the predictive power of a model in biology is quite low. It seems to us that if the prediction (e.g., a phylogenetic tree reconstructed) of a model is correct in 80% of the cases, it is a good model at least at the present time.” From Masatoshi Nei and Sudhir Kumar, 2000, Molecular Evolution and Phylogenetics, (p85):
When a result is only 80% certain, it can be completely wrong. We either know or we don’t know. Knowing with 80% certainty or anything less than 100% means we don’t know. We are much better off without it because it often leads the non-specialists into the wrong idea that we know with 100% certainty. Does not everyone in academic think that we are 100% certain that chimp is closest to humans when in fact we are only 80% certain and can therefore be completely wrong? When they then act and work based on that knowledge (they have been doing just that for years now), should we feel perfectly comfortable for misleading them into that?
Of course, nothing we know says that biology has to be different from physics. The present situation merely means that we have much to learn. When we know better, we should be able to have a model or method that is correct in 100% of the cases. Until then, some of what we are doing is just kidding ourselves. I have now offered the slow clock method as the best candidate for a method that takes into account all reality and is capable of 100% certainty (1). While the result of Chatterjee et al., like many others, does support my result on tarsiers using the slow clock method (1), I do not view their result as confirming mine, because their method is flawed. By using the same kind of method, another group could easily produce a result opposite of theirs by just picking a new set of genes (this of course has been done many times already). I of course do not view such result as valid contradiction to mine just like I do not view the result of Chatterjee et al. as valid support.
A flawed method automatically qualifies its result as meaningless, regardless whether the result happens to be consistent with reality or not. The definition of a flawed method is simply that which can turn a perfectly solid set of factual data into a false interpretation of reality. Any method that has produced conflicting interpretations has of course automatically self-proven itself false. The present situation we have with tarsiers is just one of many that says flatly it is time for a fundamental change in our method of interpreting sequence data.
Ref:
Huang, S. (2009) Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers. Available from Nature Precedings, http://hdl.handle.net/10101/npre.2009.3794.1
“Estimating the phylogeny and divergence times of primates using a supermatrix approach” Helen J Chatterjee, Simon YW Ho, Ian Barnes, and Colin Groves
BMC Evolutionary Biology 2009, 9:259 doi:10.1186/1471-2148-9-259
I sent the following comment titled “Real reason for the endless production of conflicting results on tarsiers” to the Journal’s website:
On the position of tarsiers, Chatterjee et al wrote: “The majority of molecular evidence supports the latter grouping [4,10-13] (grouping tarsiers with higher primates), although a large number of molecular studies still provide support for the Prosimii concept [14-18].”
When a method or technique can lead to two opposite results repeatedly and seemingly endlessly while only one of the two can be true, it is time to ask whether something is fundamentally missing with our method (all existing popular methods are slightly different from one another but are fundamentally the same kind). Let us start from the very beginning and examine the assumptions for our method. The key assumption for all sequence similarity based methods is that sequence dissimilarity always correlates with time of divergence. Well, is this true? We don’t have to be a specialist to know that this is sometimes true and sometimes not. Thus, for our method to be able to produce accurate and uncertainty-free result, it must take into account the reality that sequence dissimilarity sometimes does not correlate with time of divergence. Many of the sequence comparisons are not informative and should and must be excluded from our method. When they are not as is the case with all existing methods, they contribute to the high noise level that can sometimes overwhelm the signal. It is by accident that these methods sometimes give correct results and sometimes wrong results and no one knows why the difference or when to view such a result correct and final. Therefore, we have a peculiar non-scientific situation: no one is taking anyone else’s results as the final say. Never mind that we only have one true phylogeny of life on Earth. Once you know it, it is done and no more work needed. The existing methods are perfect for keeping some of us employed forever but will never give us truth. Truth is not judged by a quantitative difference in the number of studies that support it versus those against it. The correct method should produce zero number of studies that is against truth or should be immune to the production of conflicting results.
Data + method = result. The data here in molecular phylogeny is just sequence facts and cannot possibly be wrong so long one is not making sequencing errors. Thus the only way to produce a false result or conflicting results in phylogeny is through an incorrect method. Since all existing methods are perfectly capable of producing false results and have all in practice produced false results or conflicting results, it is another simple proof that the existing popular methods are simply incorrect.
By the own admission of the leading experts, the existing popular methods are flawed in the sense that they can easily produce incorrect results that are totally out of the hands of the scientists:
“Unlike the case in physics, the predictive power of a model in biology is quite low. It seems to us that if the prediction (e.g., a phylogenetic tree reconstructed) of a model is correct in 80% of the cases, it is a good model at least at the present time.” From Masatoshi Nei and Sudhir Kumar, 2000, Molecular Evolution and Phylogenetics, (p85):
When a result is only 80% certain, it can be completely wrong. We either know or we don’t know. Knowing with 80% certainty or anything less than 100% means we don’t know. We are much better off without it because it often leads the non-specialists into the wrong idea that we know with 100% certainty. Does not everyone in academic think that we are 100% certain that chimp is closest to humans when in fact we are only 80% certain and can therefore be completely wrong? When they then act and work based on that knowledge (they have been doing just that for years now), should we feel perfectly comfortable for misleading them into that?
Of course, nothing we know says that biology has to be different from physics. The present situation merely means that we have much to learn. When we know better, we should be able to have a model or method that is correct in 100% of the cases. Until then, some of what we are doing is just kidding ourselves. I have now offered the slow clock method as the best candidate for a method that takes into account all reality and is capable of 100% certainty (1). While the result of Chatterjee et al., like many others, does support my result on tarsiers using the slow clock method (1), I do not view their result as confirming mine, because their method is flawed. By using the same kind of method, another group could easily produce a result opposite of theirs by just picking a new set of genes (this of course has been done many times already). I of course do not view such result as valid contradiction to mine just like I do not view the result of Chatterjee et al. as valid support.
A flawed method automatically qualifies its result as meaningless, regardless whether the result happens to be consistent with reality or not. The definition of a flawed method is simply that which can turn a perfectly solid set of factual data into a false interpretation of reality. Any method that has produced conflicting interpretations has of course automatically self-proven itself false. The present situation we have with tarsiers is just one of many that says flatly it is time for a fundamental change in our method of interpreting sequence data.
Ref:
Huang, S. (2009) Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers. Available from Nature Precedings, http://hdl.handle.net/10101/npre.2009.3794.1
Wednesday, October 28, 2009
The MGD hypothesis in brief
A colleague recently asked to briefly summarize the MGD in laymen terms and its distinction from the modern evolution theory. I gave it a try in the following.
1) The reality of maximum genetic distance/diversity (MGD):
For any gene with a biological function, certain mutations that destruct the function will not be tolerated by the organism while those neutral or beneficial ones will. So functionally important residues cannot be mutated. For two closely related or identical individual organisms, their genetic distance will increase with time due to accumulation of mostly neutral mutations. After a while, they reach a maximum, e.g, their distance may go from 0% in the beginning to maximum 60% non-identity in 60 million years. They cannot pass the 60% maximum because any more mutations will hit the key residues and will abolish gene function and thus affect organism viability. MGD is the maximum amount of mutation a gene can tolerate in a particular organism. A gene with a MGD of 60% in organism X means that a maximum 60% of this gene’s sequence can be mutated or tolerated in organism X (the 40% non-changeable residues consists of mostly key residues as well as some important for adaptation to environment that may change form time to time or environment to environment).
The more function a gene performs, the more functional constraints on its mutation, and the less the MGD for this gene. A gene can perform related but slightly different functions in different cell types. A gene performs more functions in complex organisms with more cell types than in simple ones. Thus, complex organisms confer more functional constraints on genes. Therefore, the MGD of a gene in complex organisms is lower than that of its ortholog in simple organisms. For example the bare bone function of a gene in a single cell organism may require only 30% key or non-changeable residue. The same gene in a complex multicell organism will on top of the bare bone function gain extra key residues that will play important functions only relevant to complex organisms. The first example of this kind of CAPS (complexity associated protein sectors) is recently described in this Cell paper (1). And also see my comment on the paper at the Cell website (2).
2) The reality of fast and slow evolving genes:
Fast evolving/mutating genes reach MGD faster than slow mutating genes. Once a gene reaches MGD, genetic distance between two species as measured by this gene will no longer correlate with time. Thus, only slow evolving genes prior to reaching MGD are informative for phylogeny.
3) The modern evolution theory fails to recognize two key realities:
All existing methods of molecular phylogeny rely on assumptions that are not 100% true. They assume that genetic distance always correlates with time of divergence, which is not at all the case in reality. They do not take into account two key realities: the MGD and the difference between slow and fast evolving genes. Thus, their failure to take into account all major realities guarantees that they cannot produce conclusive and correct phylogenies.
4) The slow clock method, the first method that takes into account all reality:
The slow clock method based on the MGD is the first phylogeny method that is based on a 100% true description or pattern of reality. That is, genetic distance always correlates with time of divergence only for slow evolving genes prior to reaching MGD. The slow clock method is described here (3).
Ref.
1. Halabi, N., Rivoire, O., Leibler, S., and Ranganathan, R. (2009). Protein sectors: evolutionary units of three-dimensional structure. Cell 138, 774-786.
2. Huang, S. (2009) Complexity associated protein sectors, comment on Cell website, http://www.cell.com/comments/S0092-8674%2809%2900963-5
3. Huang, S. Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers . Available from Nature Precedings (2009)
4. Huang, S. (2009) Inverse relationship between genetic diversity and epigenetic complexity. Preprints at Nature Precedings, http://precedings.nature.com/documents/1751/version/2
I hope you find this helpful and you are always welcome to come to me with any questions. I may not have expressed in the best possible way. I necessarily simplified things more than I wished given that you only want a brief description. For more accurate descriptions, my papers would be a more reliable source.
1) The reality of maximum genetic distance/diversity (MGD):
For any gene with a biological function, certain mutations that destruct the function will not be tolerated by the organism while those neutral or beneficial ones will. So functionally important residues cannot be mutated. For two closely related or identical individual organisms, their genetic distance will increase with time due to accumulation of mostly neutral mutations. After a while, they reach a maximum, e.g, their distance may go from 0% in the beginning to maximum 60% non-identity in 60 million years. They cannot pass the 60% maximum because any more mutations will hit the key residues and will abolish gene function and thus affect organism viability. MGD is the maximum amount of mutation a gene can tolerate in a particular organism. A gene with a MGD of 60% in organism X means that a maximum 60% of this gene’s sequence can be mutated or tolerated in organism X (the 40% non-changeable residues consists of mostly key residues as well as some important for adaptation to environment that may change form time to time or environment to environment).
The more function a gene performs, the more functional constraints on its mutation, and the less the MGD for this gene. A gene can perform related but slightly different functions in different cell types. A gene performs more functions in complex organisms with more cell types than in simple ones. Thus, complex organisms confer more functional constraints on genes. Therefore, the MGD of a gene in complex organisms is lower than that of its ortholog in simple organisms. For example the bare bone function of a gene in a single cell organism may require only 30% key or non-changeable residue. The same gene in a complex multicell organism will on top of the bare bone function gain extra key residues that will play important functions only relevant to complex organisms. The first example of this kind of CAPS (complexity associated protein sectors) is recently described in this Cell paper (1). And also see my comment on the paper at the Cell website (2).
2) The reality of fast and slow evolving genes:
Fast evolving/mutating genes reach MGD faster than slow mutating genes. Once a gene reaches MGD, genetic distance between two species as measured by this gene will no longer correlate with time. Thus, only slow evolving genes prior to reaching MGD are informative for phylogeny.
3) The modern evolution theory fails to recognize two key realities:
All existing methods of molecular phylogeny rely on assumptions that are not 100% true. They assume that genetic distance always correlates with time of divergence, which is not at all the case in reality. They do not take into account two key realities: the MGD and the difference between slow and fast evolving genes. Thus, their failure to take into account all major realities guarantees that they cannot produce conclusive and correct phylogenies.
4) The slow clock method, the first method that takes into account all reality:
The slow clock method based on the MGD is the first phylogeny method that is based on a 100% true description or pattern of reality. That is, genetic distance always correlates with time of divergence only for slow evolving genes prior to reaching MGD. The slow clock method is described here (3).
Ref.
1. Halabi, N., Rivoire, O., Leibler, S., and Ranganathan, R. (2009). Protein sectors: evolutionary units of three-dimensional structure. Cell 138, 774-786.
2. Huang, S. (2009) Complexity associated protein sectors, comment on Cell website, http://www.cell.com/comments/S0092-8674%2809%2900963-5
3. Huang, S. Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers . Available from Nature Precedings
4. Huang, S. (2009) Inverse relationship between genetic diversity and epigenetic complexity. Preprints at Nature Precedings, http://precedings.nature.com/documents/1751/version/2
I hope you find this helpful and you are always welcome to come to me with any questions. I may not have expressed in the best possible way. I necessarily simplified things more than I wished given that you only want a brief description. For more accurate descriptions, my papers would be a more reliable source.
An old paper and the MGD
In recent email discussions with one of the pioneers of molecular evolution, I became aware of a 1986 paper that suggested the idea of a limit on protein sequence divergence, similar to the MGD. But these authors only recognized a limit for bacteria but failed to see similar limit also exists for nearly all organisms regardless of time of divergence, so long evolution is long enough or more than a few million years. They failed to see the inverse relationship between 'limit' and organismal complexity. They correctly recognized that the limit is determined by function but failed to see the key role of epigenetic complexity in adding more limit in addition to that determined by barebone function. They also did not explicitly point out that the idea of limit is contradictory to the molecular clock paradigm that does not recognize the concept of limit and assumes that everything is more or less on a linear range of divergence during the past 3 billion years of life.
Meyer, T. E., M. A. Cusanovich, and M. D. Kamen. 1986. Evidence against use of bacterial amino acid sequence data for construction of all-inclusive phylogenetic trees. Proc. Natl. Acad. Sci. USA 83:217–220.
abstract
It has been proposed that phylogenetic trees, intended to show divergence of eukaryotic protein and nucleic acid sequences, be extended to include those from bacteria. However, we have compared the amino acid sequences of 18 of the most divergent mitochondrial cytochromes c with those of 18 bacterial cytochromes c2 and have found that the average percentage difference between these mitochondrial cytochromes c and cytochromes c2 was not significantly greater than that among the cytochromes c2 alone. The large discontinuities in physical-chemical properties recognized between the prokaryote and eukaryote cytochromes render it highly improbable that members of the two classes should be no more different from one another than members of either class alone, assuming that sequence differences can accurately reveal evolutionary divergence. Instead, we propose that divergent amino acid sequences approach a limit of change considerably less than for comparison of random sequences. This limit of change presumably is determined by the structure/function relationship. When two homologous protein sequences have reached such a limit, convergence or back-mutations and parallel mutations become as frequent as divergent mutations. As two diverging proteins approach this steady-state condition, sequence differences no longer reflect the numbers of mutations resulting in amino acid substitution and therefore species cannot be positioned on a phylogenetic tree. Insertions and deletions are less reversible than are amino acid substitutions and, provided they are well-documented, might be more reliable indicators of bacterial relationships. Nevertheless, we suggest that data available on bacterial protein sequences do not permit construction of all-inclusive phylogenetic trees. Comparisons of protein and rRNA trees suggest that similar restrictions apply to use of rRNA sequence data.
Meyer, T. E., M. A. Cusanovich, and M. D. Kamen. 1986. Evidence against use of bacterial amino acid sequence data for construction of all-inclusive phylogenetic trees. Proc. Natl. Acad. Sci. USA 83:217–220.
abstract
It has been proposed that phylogenetic trees, intended to show divergence of eukaryotic protein and nucleic acid sequences, be extended to include those from bacteria. However, we have compared the amino acid sequences of 18 of the most divergent mitochondrial cytochromes c with those of 18 bacterial cytochromes c2 and have found that the average percentage difference between these mitochondrial cytochromes c and cytochromes c2 was not significantly greater than that among the cytochromes c2 alone. The large discontinuities in physical-chemical properties recognized between the prokaryote and eukaryote cytochromes render it highly improbable that members of the two classes should be no more different from one another than members of either class alone, assuming that sequence differences can accurately reveal evolutionary divergence. Instead, we propose that divergent amino acid sequences approach a limit of change considerably less than for comparison of random sequences. This limit of change presumably is determined by the structure/function relationship. When two homologous protein sequences have reached such a limit, convergence or back-mutations and parallel mutations become as frequent as divergent mutations. As two diverging proteins approach this steady-state condition, sequence differences no longer reflect the numbers of mutations resulting in amino acid substitution and therefore species cannot be positioned on a phylogenetic tree. Insertions and deletions are less reversible than are amino acid substitutions and, provided they are well-documented, might be more reliable indicators of bacterial relationships. Nevertheless, we suggest that data available on bacterial protein sequences do not permit construction of all-inclusive phylogenetic trees. Comparisons of protein and rRNA trees suggest that similar restrictions apply to use of rRNA sequence data.
Tuesday, September 22, 2009
Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers
I posted a new manuscript at Nature Precedings:
http://precedings.nature.com/documents/3794/version/1
titled: Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers
Abstract
Interpretations of molecular data by the modern evolution theory are often sharply inconsistent with paleontological results. This is to be expected since the theory is only true for microevolution and yet fossil records are mostly about macroevolution. The maximum genetic diversity (MGD) hypothesis is a more coherent and complete account of evolution that has yet to meet a single contradiction. Here, molecular data were analyzed based on the MGD to resolve key questions of primate phylogeny. A new method was developed from a novel result predicted by the MGD: genetic non-equidistance to a simpler taxon only in slow but not in fast evolving sequences given non-equidistance in time. This ‘slow clock’ method showed that humans are genetically more distant to orangutans than African apes are and separated from the pongid clade (containing orangutan and African apes) 17.3 million years ago. Also, tarsiers are genetically closer to lorises than simian primates are, suggesting a tarsier-loris clade to the exclusion of simian primates. The validity and internal coherence of the primate phylogeny here were independently verified. The molecular split time of human and pongid calibrated from the fossil record of gorilla, or the fossil times for the radiation of anthropoids/mammals at the K/T boundary and for the Eutheria-Metatheria split in the Early Cretaceous, were independently confirmed from molecular dating calibrated using the fossil split times of tarsier-loris and two other pairs of mammals (mouse-rat and opossum-kangaroo). This remarkable and unprecedented concordance between molecules and fossils provides the latest confirmation of the inseparable unity of genotype and phenotype and the unmatched value of MGD in a coherent interpretation of life history.
One week ago, I also sent the manuscript to a few dozen colleagues to seek their comments. None have responded with any scientific comments. Below is my email to them:
Thanks again for the helpful discussions on the primate fossil literature in connection with my molecular results on primate phylogeny. As promised I am sending the full manuscript for your critical reading, entitled: “Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers.” I also here send it to a select group of colleagues, most of whom I either communicated with before or whose works I have cited in the manuscript here. Any comments will be greatly appreciated. You will be most welcome if you have any information you can share that would either invalidate or support the work.
Since the work contradicts the paradigm, a tip to help understand it is to assume that everything you know about the molecular clock and the neutral theory is wrong for macroevolution while fine for microevolution. It also helps to know in order for you not to immediately view it crazy that the work was from a professional who is the only person in 46 years to finally catch a major mistake made by the founders of the molecular clock idea. Not to be immodest but just in case you automatically assume your view superior to mine simply because it is the party line for 46 years. The clock and the neutral theory should never have been invented in the first place for macroevolution and should never lasted/dominated for as long as nearly a half century if the mistake had been caught earlier. You will read about this mistake in the introduction of the attached manuscript. Such mistake of course automatically invalidates all of the deductions of that mistake, which include all existing molecular datings on macroevolution events. Thus, as things stand today, we either have no molecular dating information on human-ape split or any macroevo spilt for that matter or we have such information here in this manuscript correctly calculated for the first time. I know it is correct from the simple fact that it is completely (rather than only partially as in previous work) consistent with the well established fossil records as well as internally coherent.
So, if there is anything in the manuscript that may seem insane on first glance, just think two more times and remember Emily Dickinson: “Much madness is divinest sense, To a discerning eye; Much sense the starkest madness.” Most importantly for understanding the work, a person must fancy himself a disinterested seeker of truth, as a real scientist should be. As Sri Ram said it: “Only a disinterested search can result in Truth, for every form of self-interest will lead only to a creation which will serve that self-interest.”
Good luck to you all.
Sincerely,
Shi Huang, Ph.D
Professor
Central South University
Monday, September 14, 2009
My comment on CAPS finally appeared on Cell website
It took more than two weeks and a push note from me for Cell to finally publish my comment on CAPS related to the recent Cell paper: "Protein Sectors: Evolutionary Units of Three-Dimensional Structure". See my comment on the Cell website here: http://www.cell.com/comments/S0092-8674%2809%2900963-5
My push note to Cell below:
Dear Editor,
It has taken a lot longer than usual for you to make a call on my previous comment "complexity associated protein sectors". I thought I just write to check that you are still in touch. I realize that my comment is a bit challenging to the paradigm. But there is nothing in it that is non-scientific. If it has scientific value, which it does, it should not be suppressed simply because it challenges or does not support the paradigm. If the comment is mistaken and the paradigm is rock solid, it would be me rather than the paradigm that will suffer the humiliation. If I am right and the paradigm wrong, it should not be Cell's responsibility to defend the paradigm at all costs. So what is the problem? Cell has nothing to lose if a comment on its website is mistaken but would lose a lot if it is made known that it actively suppresses scientific opinions (for the sake of what? money?). Especially when that opinion may represent the real knowledge. Cell could only gain its status as a disinterested truth seeker if it allows scientific opinions of all kinds to compete.
Look forward to hearing from you soon on my previous comment. If you need more time to make your decision, fine. If you decide not to publish it, please inform me with specific scientific reasons. I highly encourage you to be on the side of a disinterested truth seeker.
BTW, I dont mean to publish this enquiry here, I wrote it here simply because I have no other way of contacting you.
Shi Huang, Ph.D.
Professor
Central South Univ.
Tuesday, September 1, 2009
Complexity Associated Protein Sectors (CAPS), new evidence for the MGD hypothesis
A Cell paper two weeks ago reports an important and beautiful result on protein sequence conservation and evolution (1) (free open access http://www.cell.com/fulltext/S0092-8674(09)00963-5) The result contradicts the modern evolution theory but is a precise prediction of the more complete evolution theory, the maximum genetic diversity hypothesis (MGD) (2, 3).
The modern evolution theory mainly consists of natural selection of Darwinism and random drift of the neutral theory. The theory makes no distinction between microevolution and macroevolution and was originally a theory of microevolution or population genetics. It was invented by population geneticists based on a complete ignorance of epigenetics, the other half of heredity equally important if not more important for determining heritable phenotypes. A factual observation is explained either by natural selection or its negation (random drift) depending on which one works better. The reason why a negation of Darwinian natural selection can be accorded equal weight in the modern evolution theory is because natural selection is largely irrelevant to or contradicted by molecular evolution for which the clock/neutral theory seems to superficially work if one overlooks the numerous contradictions of its own. No evolution biologist has ever claimed that the modern evolution theory has no factual contradictions. In truth, however, all the contradictions are about macroevolution. The theory essentially has no contradiction for the domain of microevolution or population genetics for which it was originally invented and should never have been allowed to apply outside of it.
An obvious difference between microevolution and macroevolution is that the latter involves a change in organismal or epigenetic complexity as roughly defined by the number of cell types or the number of epigenetic molecules. With microevolution only, bacteria would stay forever as bacteria, and would never be able to evolve into complex multicellular organisms.
As reported by the Cell paper, one portion of a protein of S1A family protease, termed the blue sector (arbitrary color to be different from two other sectors of red and green), is much more conserved in vertebrates than in invertebrates (Figure 6B of the Cell paper) and is not related to enzyme activity. It represents a domain specific to vertebrates. The existence of sectors in a protein, the blue sector in this case, that can differentiate complex vertebrates from simple invertebrates cannot be explained by the modern evolution theory. Thus the paper made no attempt to discuss the blue sector in connection with any evolution theory, perhaps in order not to openly embarrass the paradigm and thus have a chance to pass the peer censorship of Cell. Here is why. To explain the blue sector by natural selection, one must invoke that vertebrates as a whole encounter an entirely different natural environment from that of invertebrates, which is simply not the case. Even if so, it needs one additional wild ad hoc speculation that natural selection only acts on vertebrates but not on invertebrates, which is unlikely and inconsistent with Darwinism. To explain the blue sector by random drift would require neutrality for most of the amino acid positions in this sector, which is also simply not the case. Because if it is, the blue sector would never have been discovered in the first place as a group of correlated amino acids.
So what does the blue sector say about actual evolutionary mechanisms? A key question that should be discussed by the Cell paper but was unfortunately not. First, it adds one more outstanding fact to the long list of facts that contradict the modern evolution theory. Second, every fact that contradicts the modern evolution theory has been automatically found to be evidence for the MGD and the new result of the Cell paper is no exception. The MGD treats the modern evolution theory as true only for microevolution and suggests that macroevolution is distinctly different and involves a change in epigenetic complexity. One is mostly about pure genetic changes such as point mutations whereas the other is mostly about epigenetic changes, e.g., rearrangement of large segments of chromatin and gene expression patterns.
A good analogy is house building or any kind of man-made construction. We need both bricks/building blocks and architecture plan/map. Microevolution is about changing brick types, like from clay to rock. Macroevolution is about changing architecture plans, like from 1 story to 100 story buildings. And there is a self-evident inverse relationship between plan and bricks: the more complex the building plan, the more restriction on the variation in building blocks. It is always a sign of great science if one can express it in terms of common sense language, as well put by Einstein: “Most of the fundamental ideas of science are essentially simple, and may, as a rule, be expressed in a language comprehensible to anyone.” It is obviously non-sensible to ordinary people for any theory to be equivalent to saying that changing brick type alone can change the architectural style of buildings.
An increase in epigenetic complexity will lead to a decrease in genetic diversity as measured by point mutations due to a self-evident inverse relationship between genetic diversity and epigenetic complexity (2, 3). A gene in complex organisms encounters more epigenetic constraint than in simple organisms and is thus less tolerant of point mutations. Macroevolution towards higher epigenetic complexity involves a suppression of point mutations, and in this sense is the exact opposite of microevolution (ref 2-5). Thus the MGD predicts that protein or DNA sequence sectors that are non-constrained in simple organisms would become constrained in complex organisms even though such sectors may play no role in enzyme function. The blue sector of S1A protease is the first example of such Complexity-Associated-Protein-Sector (CAPS) or more generally Complexity-Associated-Sequence-Sectors (CASS) to also include DNA. Epigenetic complexity puts maximum CAPS on sequence divergence.
Finally, a simple thought experiment on how the blue sector may illustrate the distinction between micro and macro evolution. A common ancestor gave rise to two invertebrate species A and B and a vertebrate species C within a couple of million years during the Cambrian period. After 550 million years of evolution, A and B are 40% non identical in a trypsin of 240 aa. Most of the blue sector residues are located in the non-identical regions. Both A and B contributed equally to the non-identity between them because they are similar in complexity or in their tolerance level to point mutations. On the other hand, C and A or C and B are also 40% non-identical. Most of the blue sector residues of C are also located in the non-identical region. However, mutations in the blue sector are not neutral to C (while neutral to A and B) because C is more complex, and so have happened much less frequently than the corresponding positions of A or B. Thus, while the mutation rate of A or B can be calculated as is done by the modern evolution theory as 40% x 240/2/550 = 0.087 aa per million year, the same cannot and should not be done for C.
Unfortunately, the same has in fact been done and is being done daily for C under the existing paradigm in the past 46 years, resulting in numerous contradictions with the facts of macroevolution in term of both the fossil record and the DNA record such as the genetic equidistance result of Margoliash in 1963 (6), the most remarkable result of molecular evolution. The molecular clock/neutral theory was invented to account for the numerical feature of this result but should never have been invented in the first place and lasted as long as it has been if another feature, the overlap feature, of this result had been appreciated 46 years ago rather than just now as a direct result of inventing the MGD. As things stand today, we either have no theory to explain the overlap feature of the equidistance result as well as numerous other facts such as CAPS or we have a perfect one in the MGD.
Ref.
1. Halabi, N., Rivoire, O., Leibler, S., and Ranganathan, R. (2009). Protein sectors: evolutionary units of three-dimensional structure. Cell 138, 774-786.
2. Huang, S. (2008) Histone methylation and the initiation of cancer. Cancer Epigenetics, Ed. Tollefsbol, T., CRC Books.
3. Huang, S. (2009) Inverse relationship between genetic diversity and epigenetic complexity, Submitted. Preprint available, http://precedings.nature.com/documents/1751/version/2
4. Gago, S., et al., (2009) Extremely high mutation rate of a hammerhead viroid. Science 323: 1308
5. Zimmer, C. (2009) Fast-mutating viroids hold clues to early life. Science magazine blog, http://blogs.sciencemag.org/origins/2009/03/fast-mutating-viroids-hold-clu.html
6. Margoliash, E. (1963) Primary structure and evolution of cytochrome C. PNAS, 50:672-679
Friday, August 28, 2009
Darwinists self destruct when self defend
Let us do a few necessary/inevitable logical deductions from the typical claims of a Darwinist like Ken Weiss and others and see where they may lead us. Ken Weiss: “Any rule an evolutionary biologist can come up with, nature can break.”
The rules/hypotheses of Darwinists include a few like the following:
1. The very rule itself that ‘any rule an evolutionary biologist can come up with, nature can break.”
2. Variations are random/chance.
3. There is no God doing any selection. There is no artificial/mind selection and only natural selection, at least before the appearance of human mind.
The following are the exceptions to each of the above. They must be true if Darwinists are right that “any rule an evolutionary biologist can come up with, nature can break”:
1. There is such a rule that has no exceptions.
2. Some variations are due to intention or not random.
3. There is a God doing artificial selection during evolution.
These logical exercises are meant to illustrate the absurdity of the position of no absolute truth/certainty/rule in evolution. It is a self defeating position and a double edged sword. Darwinists cannot escape self-destruction when they use it for self-defence of their contradiction-laden theory.
A person caring only about the disinterested search for truth can only have one possible position. There must be a law of evolution that has no exceptions. Nothing can break it. Not accidents, not mother nature, and not God.
"Only a disinterested search can result in Truth, for every form of self-interest will lead only to a creation which will serve that self-interest." by N. Sri Ram
Friday, August 21, 2009
Either chance or intention (no other alternatives), in Darwin's own words
In Darwin's words:
"I cannot look at the universe as the result of blind chance, yet I can see no evidence of beneficent design, or indeed of design of any kind."
"This [conviction in the existence of God] follows from the extreme difficulty or rather impossibility of conceiving this immense and wonderful universe, including man with his capacity of looking far backwards and far into futurity, as the result of blind chance or necessity."
These statements by Darwin clearly shows that he sees only two possible choices for man, either chance or God, for explaining the universe. And his is a theory of chance, as is clear to every sensible human being including Darwin himself but oddly enough not to most of his most outspoken followers.
Today's Darwin followers, a very small fraction of scientists who studies evolution for a living and ranks among the most non-scientific among scientists (those who refuse to allow their theory to be falsified by a contradicting test result), outrageously claim that there is actually a third alternative, i.e., "not pure chance and not pure determination."
In Ernst Mayr's words:
"No one has stated this better than Sewall Wright: “The Darwinian process of continued interplay of a random and a selective process is not intermediate between pure chance and pure determination, but in its consequences qualitatively utterly different from either.”
So, these so called evolution scientists obviously have revised Darwinism and made Darwin look stupid, not to mention most of us fellow human beings. Should not they be awarded a Noble for their great discovery of a third alternative besides chance and intention? Well, last time I checked, not a single person has won a Nobel for his contribution to evolution theory. For that to happen, a person would have to first create a shorter word for such a stupid concept of "not pure chance and not pure determination". But unfortunately, chance and intention has already every relevant concepts covered. There is nothing left besides those two for Darwin revisionists to create a name for.
A man was found dead tonight. It could only be either chance or intention, at least those would be the only two possible alternatives worth considering to a police. The creation of human beings in this universe can only be either chance or intention. The death or extinction of the human race in this universe can only be either chance or intention. Most Darwinists, like Steven Gould, say that human may not appear if evolution is repeated, thus viewing human as the result of chance.
Note that intention can allow chance a role in the universe. Like I intentionally use chance or tossing dice to select whether I should serve first. So, the existence of intention does not necessarily rules out any role for chance in this universe. And therefore, the existence of chance as we do seem to see in this universe does not rule out intention. In contrast, a chance theory necessarily rules out intention. When we say either chance or intention, the concept of intention includes any position anywhere from 100% intention to only 0.000...1% intention, and the concept of chance means 0% intention.
Darwinists say that natural selection is not random. By this, they want common folks to think that human is not a result of pure chance. So, what is their prediction if evolution is repeated? would human evolve again? Darwin himself believes in either chance or intention. And it is easy prediction for either chance or intention: if chance, no human; if intention, yes again human. The third alternative of "not pure chance and not pure determination" predicts what? Not pure human and not pure no human? By the admission of most Darwinists, the answer is no human. So for all practical matters that are relevant and important to common folks, their theory is no different from a pure chance theory. Theirs is as far away from an intention theory as any pure chance theory can be.
Telling people that natural selection is not random is not wrong but is a complete nonsense carrying zero useful information. It is exactly like telling a father who has just lost his son to an earthquake that bleeding to death the process is not random and thus he should not view the death of his son random. To say "bleeding to death the process is not random" is not wrong but is such a trivial and irrelevant truth to say and would only confuse the father.
Natural selection the process is not random is such a trivial and irrelevant truth that even Darwin did not bother to say during his entire life. Because he knows that whether it is random or not has no bearing on the random nature of the result of selection, which can only be random in a world without intention.
Again, making a big deal of the non random nature of the selection process can fool no one other than those very few who kept repeating such trivial and irrelevant truth. They probably believe that a lie repeated enough can become truth. Well, they need to first convince the Nobel committee before the common folks. Genuine scientific truth always trickles down from top/elite to bottom/common folks. There are just too many genuine elite scientists, including most mathematicians, most physicists, and most real biologists like myself who would if they have a choice never go into a branch of biology like evolution that has a track record of zero Nobel laureates (a rough measure of its non-scientific nature as is currently practiced), who would simply laugh at any theory that do have and do allow contradictions, regardless whether it is Darwin's or God's theory.
Wednesday, August 19, 2009
All existing evolution theories have/allow contradictions and hence are non-testable
Darwin followers never said that their theory has no exceptions. Here are a few typical claims:
“Unlike the case in physics, the predictive power of a model in biology is quite low. It seems to us that if the prediction (e.g., a phylogenetic tree reconstructed) of a model is correct in 80% of the cases, it is a good model at least at the present time.”
Masatoshi Nei and Sudhir Kumar, 2000, Molecular Evolution and Phylogenetics, p85.
“any rule an evolutionary biologist can come up with, nature can break.”
From Professor Ken Weiss’s Blog page of July 13, 2009, http://ecodevoevo.blogspot.com/2009/07/rules-of-nature.html
A common sense and logical view of mine on why any theory must not allow a single contradiction in order to qualify as scientific or testable:
In mathematics or physics, one exception is sufficient to doom any theory. The science of biology or any scientific discipline for that matter should not be held to a lower standard. When one allows exceptions, one has effectively and automatically rendered the theory non-testable and non-scientific. Think about it: if a test turns out to be against the theory, would the theory still stand as correct? Yes, if one allows exceptions. Thus, such a theory can never be falsified by the scientific method. That theory would be no different from a false theory that happens to explain a fraction of nature while being contradicted by the rest. The only way to distinguish a true theory from a false or incomplete one is to see if it has not a single factual exception within its domain of application or relevance.
The worst theory possible would still be able to explain at least one factual observation, namely, the fact itself that directly provoked the theory or the tautology. For example, apple falls because it is the intrinsic nature of apple to fall. Thus, to be able to explain a small fraction of all relevant facts while being contradicted by the rest is not evidence of a true theory but is evidence of an incomplete or false theory.
I have no patience with such typical self-serving and self-deceiving claims that you don’t expect a theory of evolution to have no contradictions since most things are chance. The one thing that all genuine science like mathematics and physics have taught us is that it would take a miracle for an incomplete theory to have no contradictions and it would equally take a miracle for a complete theory to encounter a single contradiction in nature. The difference between truth and falsehood is not quantitative or measured by the difference in the number of contradictions but is qualitative.
There can be countless incomplete or false theories with each accounting for a few facts but there can only be one unique true theory that accounts for all facts within its domain of application. Until evolutionary biology has such a theory that has not a single contradiction, it is not real science. But I still view the daily work of biologists as scientific even if being misguided by an incomplete theory because the facts that they collect will be useful for looking for the true theory and fact collection rather than theory building is what they do for a living. In this sense, the taxpayers’ money is well spent indeed.
Newton physics does not work in the microworld and Newton followers have no trouble admitting it. Darwinism would not have a single exception if it is limited to microevolution such as drug resistance in bacteria. It only encounters exceptions when being applied to domains such as macroevolution where it is irrelevant and false. Darwinists could easily meet the no contradiction standard if they could just be honest and specific about where their theory works and where it does not.
Natural selection is random but artificial selection is not
Contrast between natural selection (NS) and artificial selection (AS). Artificial selection has human mind as the selector. It was used by Darwin as an analogy to natural selection. D
- Slow though the process of selection may be, if feeble man can do much by artificial selection, I can see no limit to the amount of change, to the beauty and complexity of the co adaptations between all organic beings, one with another and with their physical conditions of life, which may have been effected in the long course of time through nature's power of selection, that is by the survival of the fittest.
NS AS
Intention.............................no yes
Purpose..............................no yes
Selector...............................random non random/mind
Selection process................non random non random
Selection outcome...............random non random
Overall.................................Random Non random
Next time you hear someone says that natural selection is the opposite of random, ask him what then is artificial selection? Mind and no mind are opposites, and if one is non random, its opposite can only be random.
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