Saturday, August 14, 2010

Some paper concludes that complex organism has more functional bases

The conclusion of a recent paper last week, in particular this last sentence from the paper’s abstract, says: "This suggests that, rather than genome size or protein-coding gene complement, it is the number of functional bases that might best mirror our naïve preconceptions of organismal complexity." (1)

The paper is still in part based on the neutral theory that is not true in my opinion for macroevolution. Thus, it concludes that human has about 90% neutral bases while only 10% constrained functional bases. But my study based on the First Axiom of Biology suggests that human has only about 0.1% neutral bases, equivalent to the number of SNPs we find in humans (manuscript in preparation).

So, if the paper’s methodology and interpretation are in part based on the neutral theory, it would not be appropriate to consider its conclusions valid or meaningful. But it is still interesting to see that someone could somehow come to a conclusion that is at least partly in line with the First Axiom of Biology, which says that genetic diversity is inversely related to epigenetic complexity (2). The more complex the organism, the less random variation in the building blocks such as DNA. Or, the more complex the organism, the more the functional bases, and the less the neutral bases.

Reference:
1. Meader, S., Ponting, C.P., and Lunter, G. Massive Turnover of Functional Sequence in Human and Other Mammalian Genomes, (2010) Genome Research. Published on line August 6, 2010. http://genome.cshlp.org/content/early/2010/08/05/gr.108795.110.full.pdf

2. 1. Huang, S.(2009) Inverse relationship between genetic diversity and epigenetic complexity. Preprint available, Nature Precedings;


Here is the abstract of the paper:
Despite the availability of dozens of animal genome sequences, two key questions remain unanswered: first, what fraction of any species‟ genome confers biological function, and second, are apparent differences in organismal complexity reflected in an objective measure of genomic complexity? Here, we address both questions by applying, across the mammalian phylogeny, an evolutionary model that estimates the amount of functional DNA that is shared between two species‟ genomes. Our main findings are, first, that as the divergence between mammalian species increases, the predicted amount of pairwise shared functional sequence drops off dramatically. We show by simulations that this is not an artefact of the method, but rather indicates that functional (and mostly non-coding) sequence is turning over at a very high rate. We estimate that between 200 and 300 Mb (~6.5 – 10%) of the human genome is under functional constraint which includes 5-8 times as many constrained non-coding bases than bases that code for protein. By contrast, in D. melanogaster we estimate only 56-66 Mb to be constrained, implying a ratio of non-coding to coding constrained bases of about 2. This suggests that, rather than genome size or protein-coding gene complement, it is the number of functional bases that might best mirror our naïve preconceptions of organismal complexity.

15 comments:

Society of Intelligent Design said...

Interesting post and interesting blog. I have a couple of questions.
Firstly, what is the first and second axiom of biology?
Secondly, by your interpretation of molecular equidistance -- an interpretation I believe is the correct interpretation, demonstrating the inadequacy of Darwinism -- but by your interpretation of molecular equidistance, what role does "junk" DNA play in your interpretation?

Livingstone Morford

gnomon said...

The First Axiom of Biology states that genetic diversity is inversely related to epigenetic complexity. The second axiom of biology is yet to be discovered. Google the term to find my recent papers on this Axiom.

Junk DNA also means neutral DNA. The more complex the organism, the less junk/neutral DNA it has. This inverse relationship between junk DNA and organismal complexity is equivalent to the First Axiom of Biology and is essential to my interpretation of molecular equidistance or genetic equidistance.

Society of Intelligent Design said...

Thank you very much for this informative reply. I have to concede that I am new to the molecular equidistance debate, but I've been following your threads around the internet, and have yet to see an effective rebuttal to your interpretation of molecular equidistance. I still however have not read your paper on the MGD, which I will do soon. Can you give me a brief background information on what your hypothesis is?
Also, according to the MGD, would the amoeba be less complex than humans since the amoeba has more neutral bases?

Livingstone Morford

P.S. Being the author of two technical papers in biochemistry (manuscript under review), I can understand most technical terminology ; )

gnomon said...

Below I describe the main idea of MGD in brief, which is handy for me as I have prepared it before for another scientist who requested it.

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 a Cell paper, and see my comment on the paper at the Cell website (http://www.cell.com/comments/S0092-8674%2809%2900963-5).

2) Macroevolution is the opposite of microevolution:
The MGD hypothesis defines macroevolution and microevolution differently from the standard definition and considers them distinctly different. Macroevolution involves major changes in epigenetic complexity or organismal complexity as defined by the number of cell types and of epigenetic molecules. Microevolution involves no major changes in epigenetic complexity and is mostly about pure genetic changes such as random point mutations. The MGD says, as demanded by the First Axiom of Biology and evidenced by all known facts, that an increase in epigenetic complexity during macroevolution is associated with a suppression of genetic diversity or point mutations. Thus, macroevolution is the opposite of microevolution. While randomness is good and a source of innovation/variation for microevolution, it is mostly harmful for macroevolution of greater complexity and must be suppressed.

3) 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. The modern evolution theory fails to recognize these two key realities, the MGD and the difference between fast and slow evolving genes, and therefore cannot possibly produce a correct phylogenetic tree of life.

Regarding the amoeba question (and all other related ones), you just need to know this that no organisms on Earth are more complex (or have more cell types) than humans.

Society of Intelligent Design said...

Very good. I hope I'm not taking your time, but I still have some more questions on the MGD.
The first question is, what about gene duplication? What role do gene duplications play in the MGD since mutations in duplicated genes are usually neutral I believe.
My second question is, what aspects of Darwinian evolution does the MGD contradict?
Thank you for your time.

Livingstone Morford

gnomon said...

Genetic diversity as the term is used in the First Axiom of Biology is mostly about genetic distance contributed by point mutations. It does not concern gene duplications which may well be an epigenetic change in addition to being a genetic one. The event of gene duplication is both genetic and epigenetic but the subsequent accumulation of mutations in the duplicated gene could contribute to the genetic diversity as the term is used here.

The key difference/contradiction between the MGD and the modern evolution theory that includes the neutral theory of Kimura and natural selection of Darwin is that the MGD treats macroevolution as the opposite of microevolution whereas the modern evolution theory treats the two the same. The MGD grants the modern evolution theory largely true for microevolution and includes it as a part of the hypothesis relevant only to microevolution. The best piece of evidence for a clear distinction between micro and macro evolution is the genetic equidistance result. It naturally also is the best piece of evidence contradicting the modern evolution theory while supporting the MGD.

The famed evolution biologist professor George Simpson said: "If the two (micro and macro) proved to be basically different, the innumerable studies on
micro-evolution would become relatively unimportant and would have minor value in the study of evolution as a whole." Indeed, Darwinism plus the Kimura theory has little value to the key phenomenon of evolution, the evolution from simple to complex.

The famed Darwinist Theodore Dobzhansky said: "We are compelled at the present level of knowledge reluctantly to put a sign of equality between the mechanisms of macro- and microevolution, and proceeding on this assumption, to push our investigations as far ahead as this working hypothesis will permit." Well, that assumption has now been proven false by countless factual observations on molecular evolution as well as priori reason. One single molecular observation, the molecular/genetic equidistance result, is sufficient to falsify that assumption. In contrast, the more complete theory MGD that does not equal macro with micro has found support in all relevant facts of molecules and fossils and has yet to meet a contradiction.

Society of Intelligent Design said...

Very good again. Yet another question I have (and I apologize with having so many questions but I really am interested in this hypothesis) is this: do we see macroevolution as you define it, occurring today? In other words, to quote you, Dr. Huang, do we see "major changes in epigenetic complexity or organismal complexity" happening today?

Livingstone Morford

gnomon said...

Thanks for the good questions. Macroevolution as in my definition occur abruptly once in a longtime (million of years). They also require ancestors that have not undergone extensive terminal differentiation. Most of today's species are terminally highly derived or differentiated. So, macroevolution would be extremely rare in today's Earth.

An example about terminal differentiation. You dont expect a die hard Darwinist to be the ancestor of a great advance in evolution theory. That ancestor could only be someone who is not committed in any way, ie, not terminally differentiated, not committed to any personal or social economic or idealogical agenda. He must be a disinterested truth seeker.

Society of Intelligent Design said...

So early in the history of life on earth, most life forms were not terminally differentiated, if I understand you correctly? And the more these life forms evolved, the more terminally differentiated they became? Please correct me if I misunderstand this aspect of the MGD hypothesis.
Also, what do you define as epigenetic or organismal complexity? Thank you very much for your time, Dr. Huang.

Livingstone Morford

gnomon said...

The MGD hypothesis is mostly concerned with interpreting the molecular record/pattern of evolution. It leaves some important questions open or to be resolved by a future more complete theory that covers a larger domain of reality, such why macroevolution of life forms only happens once and does not repeat itself? So your question does not strictly fall within the domain of the MGD hypothesis, and need not to be resolved now if all we want to do is to have a scientific interpretation of the molecular record or pattern of evolution. In fact resolving it now one way or the other would have little impact on the daily scientific research on the molecular pattern of evolution. There are numerous non mainstream evolution theories that offer various opinions on the big questions but they share one thing in common. They all have little to say on the small detailed factual observations that scientists study daily, which is why they can have little impact on scientific research, and why they cannot qualify as scientific. A scientific theory, especially a physics theory, is often about a pattern or relationship. The MGD is about a universal pattern between random noise in building blocks and the complexity of building plans, which is termed the First Axiom of Biology. It is the first evolution theory with a realistic chance to be true because it explains more facts than any other theory and does so in a contradiction free manner.

What caused gravity is of no concern if all we are practically interested in is to study the pattern of large moving objects, for which the axioms of Newton are perfect.

The definition of organismal complexity is often debated. I believe that my use of epigenetic complexity to mirror organismal complexity is close enough and intuitively sound and works for all practical concerns. Epigenetic complexity is defined by the total number of cell types and epigenetic molecules.

Society of Intelligent Design said...

Okay I just finished reading your "Inverse relationship between genetic diversity and epigenetic complexity." It is quite obvious to me that the MGD hypothesis is the only adequate explanation for the genetic equidistance phenomenon. I do however have yet another question. If a species reached its absolute maximum amount of genetic diversity, in all of its genes, would it be able to evolve more epigenetic complexity?

Livingstone Morford

gnomon said...

Yes. In fact, macroevolution of greater complexity often only happens after an ancestor species have evolved a level of genetic diversity close to the maximum genetic diversity. It only occurs after a long stasis period (hence the punc-equ phenomenon). The stasis period is usually long enough for MGD to be reached. Most species today have reached MGD. What this means is that all possible variations of a genome allowed within a MGD would have a chance to exist if only for a while during the stasis period. Macroevolution then only occurs if one of those genome variations happens to be suitable or compatible with a higher level of epigenetic complexity. This genome version would then got partially fixed by the greater epigenetic complexity. While the individual with this genome version may undergo an increase in epigenetic complexity which then further protects that genome version from mutating away into some other noncompatible version, her sister with a near identical genome may stay the same as the ancestor species in epigenetic complexity. With time, the sister would accumulate mutations that are more suited to the life of the ancestor species, thus making her descendants genetically distinct from the new and more complex species.

If a human being is interested in converting a species into a complex one assuming he has the technology to do so, his most reasonable method would be to first study the structure function relationship of a gene in order to know the properties of all the possible variants of a gene. He would let nature do this mutation testing experiment by simply observing the natural microevolution process of mutation, drift and adaptation. He would then select the individual with the variant most sutible for making a complex species. Thus he would almost certainly not start his creation of the new species until he has a chance to observe most of the variants of the ancestor species, which means that he will wait until the ancestor species has reached a certain level of genetic diversity, not necessarily have to be at the MGD but close. Since mother nature cannot possibly be less capable than a human being, her method cannot possibly be worse than the best method that humans can come up with.

Society of Intelligent Design said...

I have read the phrase "overlap" in some of your blog posts. Can you explain to me what exactly the "overlap" feature of molecular equidistance is? Thanks!

Livingstone Morford

gnomon said...

Glad that you asked since I have just written a short paragraph on the overlap feature for the introduction section of a new manuscript. It is intended for people who have not read my previous papers. Please let me know if you do not find it easily understandable.

Recent work shows that the genetic equidistance result has in fact another characteristic, the overlap feature, which has been completely overlooked for nearly half-a-century (Huang, 2010). A position where two or more species have each had a substitution event is termed an overlap position. If after speciation, two species randomly accumulate substitutions with similar rate as described by the neutral theory, then the chance for a substitution in one species to occur at the same overlap position where the other species also has a substitution should largely follow probability theory. Indeed, for microevolution of similar species such as within different strains of yeasts, the number of overlap positions is small and consistent with probability calculation based on the neutral theory. However, for macroevolution of distinct species of different biological complexity such as yeast versus drosophila or orangutan versus human, the number of overlap positions is much greater than that calculated from the neutral theory. Thus, the overlap feature is one of the best pieces of evidence for a clear distinction between macroevolution and microevolution, where macroevolution is mostly about major changes in organismal complexity whereas microevolution is not.

Ref.
Huang S (2010) The overlap feature of the genetic equidistance result, a fundamental biological phenomenon overlooked for nearly half of a century. Biological Theory 5: 40-52. http://www.mitpressjournals.org/doi/abs/10.1162/BIOT_a_00021

gnomon said...

The overlap feature of the genetic equidistance phenomenon is one of the best pieces of evidence for the MGD hypothesis and against the modern evolution theory (Huang, 2010). It is well established that most of the changeable positions in a gene in complex species are also changeable in a less complex species. When MGD has been reached during macroevolution, most of the changeable positions in any species have undergone substitutions, thus leading to a large number of overlap positions much greater than expected by chance. For microevolution of similar species over long evolutionary time so that MGD has also been reached, one also observe a large number of overlap positions much greater than expected by chance. In contrast, for microevolution of short evolutionary time scale prior to reaching MGD or for slow evolving genes, the number of overlap positions is small and consistent with calculation from probability theory.