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.

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.

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

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.

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

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

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.”

"It is remarkable how generally it is overlooked that with natual selection Dawin has introduced an entirely new and revolutionary principle which is not at all vulnerable to the objection that his theory relies entirely on accident."

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.