Junk DNA and Central Dogma formally abandoned in HoloGenomics

[June 20, 2008; connecting the dots after more than 50 years of blocking progress of understanding genome function]

Principle of Recursive Genome Function Supersedes Dogmas; By Andras Pellionisz, Online Ahead of Print; (Scientific Visionary Vindicated)

[The Principle of Recursion comprised in a single color Fig. (Not in the paper; see Supplementary Information)]

[Free Full Text of Journal Article, with clickable references, plus Supplementary Information is available]

A Eureka Moment concerning the fractal character of neurons led in turn to a novel picture of genomics where protein structures act back recursively upon their DNA code -- in outright contradiction to prevailing orthodoxy. A household name in neuroscience for his tensor network theory, Dr. András Pellionisz has recently had another far-reaching discovery borne out. This insight has now received striking confirmation in stunning results from the new field of epigenetics -- promising a whole raft of novel medical diagnoses and therapies.

Sunnyvale, Calif. (PRWEB) July 16, 2008 -- A landmark article on "The Principle of Recursive Genome Function" (received December 7, accepted December 18, 2007) by András J. Pellionisz appears online in Springer's e-Journal Cerebellum.

The paper marks the first anniversary of an historic event--the release of pilot results for ENCODE, the Encyclopedia of DNA Elements project. Building on the results of the Human Genome Project, the ENCODE effort revealed a far more complex DNA coding sequence than was ever previously imagined. "There's a lot more going on than we thought," said Collins, who was director of the National Human Genome Research Institute (NHGRI). Dr. Collins issued a mandate a year ago "the scientific community will need to rethink some long-held views".

A happy few did not need to rethink either the "central dogma of molecular biology" (Crick, 1956) or the misnomer of "junk" DNA (Ohno 1972), since they never believed them in the first place. The dictum claiming that a flow of information from proteins back to DNA "never happens" or the idea that 98.7% of the human genome should be disregarded as junk was never very believable.

As a direct response to Dr. Collins' call, the principle of recursive genome function (PRGF) in one stroke sweeps away two dogmas which prevailed for over 50 years concerning the function of the double helix.

Recursive genome function is a process whereby proteins iteratively access information packets of DNA to build hierarchies of more complex protein structures. Such recursive development is illustrated in the fractal growth of cerebellar Purkinje neuron:

[See all Figs. plus color versions here]

Starting from a primary information packet, a Y-shaped, fractal protein template is constructed by a "forward growth" process - in accord with the traditional picture - via transcription of DNA to RNA (where, in turn, RNA builds nucleic acids up into structural protein). In the course of constructing the Y-shaped template, the primary gene is turned on. Thus, the most primitive part of the process retains Watson's simplified scheme. The principle does not contradict the 'DNA makes RNA makes proteins' picture, but rather goes beyond it - dispensing with both the hitherto forbidden feedback mechanism as well as the entire notion of junk DNA.

On the contrary, the genetically crucial process known as methylation demonstrates just such a "backward" flow. In a stunning reversal of long-held views, it now appears that environmental influences can act directly on the genetic code. Moreover, methylation of DNA is not merely epigenetic, but HoloGenomic.

Dr. Alexandre Akoulitchev, Oxford University, UK (not involved in the study) says: "The PRGF of Pellionisz is helping not only his recursive algorithmic approach to the genome (FractoGene), but puts the various meanings of 'epigenetics' into the perspective of clearly defined novel axioms. The PostModern Age of Genomics (starting with his PostGenetics.org), synthesizes inconsistent interpretations and haphazard notions of "epigenetics" into a solid scientific foundation of HoloGenomics."

Leroy Hood (2003) and finally Richard Dawkins (2008) have suggested that genomics is now a branch of information science. With modern genomics becoming postmodern genome informatics, a natural question arises: What axioms will take the place of outmoded assumptions?

The traditional axioms could not put to a dignified rest because, as the wisdom has it, "data never kill theories, only better theory can kill less tenable theories."

The principle of recursive genome function addresses this fundamental, decisive role. The time has come to go public, after more than a decade of clandestine work - not even asking for support.

András Pellionisz is a biophysicist, formerly of New York University. Since heading up HelixoMetry in Silicon Valley, he has been busy assembling a portfolio in anticipation of the time when the imposing dogmas and their bulwarks would give way. A widely published author, Pellionisz remained largely silent for 15 years to spare him a collision with the powers that were.

His pioneering work in biological neural networks, aired in over a hundred publications, won him both NIH support and recognition by way of the Alexander von Humboldt Prize for Senior Distinguished American Scientists.

When Pellionisz also made a bold step and published his research on the fractal geometry of cellular development based on a recursive DNA paths (1989), his next NIH application was overlooked by his peers and the establishment maintained a double lock on genomics. Their ideology was: Don't look back on DNA, since recursion can "never happen" and even if you would, "there is only junk."

As a scientist with his first degree in engineering, he developed a neural net application for NASA, using the parallel computers of the time (so-called Transputers).

By 2005 fundamental problems with underlying axioms of genomics became too obvious. Meanwhile, millions, if not hundreds of millions were dying of junk DNA diseases while 98.7% of the human DNA was officially still considered untouchable.

Together with his fellow pioneers, Dr. Pellionisz launched the trial balloon of International PostGenetics Society. Indeed, almost a year ahead of disclosing the official conclusions of ENCODE that "junk" DNA is anything but, the IPGS became the first organization to officially abandon the misnomer at its European Inaugural in 2006. At that meeting, Pellionisz pioneered the approach of diagnosis (leading to therapy and eventual cure) of junk DNA diseases caused by fractal defects in genomic regulatory sequences.

In late 2006 a manuscript attempting to close the chapter on junk DNA was co-authored by 20 Founders of IPGS. Those suffering from "junk DNA diseases" probably wish that the manuscript was given the benefit of a peer-review.

Instead, the mounting pressure caused publication of ENCODE results 3 months earlier than planned. Thirty major papers shredded long-held views and printed staggering statements such as "the concept of genes is a myth." A deafening silence ensued.

Rather than heeding advice of Dr. Collins of "re-thinking long-held beliefs" research went "genome-wide" for more data, as next-generation sequencing made the entire genome of many species (including humans) available with rapidly melting price tag.

Application of brute force to turn out more data instead of revising axioms created its own problems, however. A dreaded DNA data deluge looms large. Without a combination of algorithmic reduction as well as building the proper computing architecture, the brute force approach of full genome sequencing and genome-wide analysis have already hit a compute- and data-wall.

The old bottleneck was "get info" (sequencing to obtain data). The new bottleneck is "use info" (understanding what sequenced data mean). The promise inherent in the Principle is that an algorithmic reduction delivers us an understanding of physiological and therefore pathological genome function in a new light. This clears the road for rapid advancement beyond a long-overdue breakthrough. In HoloGenomics, all, including non-genic conditions can now be focused upon. This is the direct response to consumers, including those who are not even patients. For those impatient enough to prevent some undesirable conditions, the principle opens an opportunity.

Ohno's "paradigm-shift" paper (indeed, a very short abstract) is difficult to obtain, and thus most people who argue about "Junk DNA" actually never read it. Therefore, please find it reproduced in full. Thomas Kuhn, in his classical treatise of "The Structure of Scientific Revolutions" could never touch on this subject, since Dr. Kuhn passed away in 1969, while the "Junk DNA" symposium abstract originated from 1972. Once one actually reads Ohno's paper, it is self-evident that a) he produced (a false) argument that the number of possible genes in the human DNA is extremely limited (thus, by necessity, much of the DNA must be meaningless "junk"), and b) he "explained" (also mistakenly) that the junk DNA litters our genome as a result of failed remnants of earlier times. During the generation (35 years) from 1972 to the death of the dogma with ENCODE (June 14, 2007) there was much degeneration of the pristine (but false) dogma to various misinterpretations, e.g. allowing for the ever increasing fact that functional, indeed, more important elements were found in the vast seas of intergenic regions than the mere function of "genes".

However, as Dr. Kuhn explains in his classic book (p. 159) the reversal of the dogma had a long way to go - and indeed there will always be "a few elderly hold-outs" sticking with the dead body of obsolete dogma. (For instance, in some countries that are set back with rigid and unproductive R&D structure, old tenured professors, morons rather, like "Larry", don't have to fear pressure to keep up with the progress of science, and their "education" of the young with obsolete dogma apparently goes on forever, unpunished - to the extent that even their daughter calls her father "stupid").

Denunciation of Ohno's false argument started immediately after the pronounciation by Ohno, in the "Discussion" by Boyer: "... It thus seems to me that the permissible number of structural loci is - as yet - a somewhat suspect way to arrive at figures of 1% structural utility to 99% junk".

"At the start of a new candidate for paradigm [i.e. that much of the regulatory DNA is not "Junk"] may have few supporters, and on occasions the supporter's motives may be suspect. Nevertheless, if they are competent, they will improve it, explore its possibilities, and show what it would be like to belong to the community guided by it. And as that goes on, if strength of the persuasive argument in its favor will increase. More scientists will then be converted, and the exploration of the new paradigm will go on. Gradually the number of experiments, instruments, articles, and books based upon the paradigm will multiply. Still more men, convinced of the new view's fruitfulness, will adopt the new mode of practicing normal science, until only a few elderly hold-outs remain. ... the man who continues to resist after his whole profession has been converted has ipso facto ceased to be a scientist."

[...The late] Dr. Susumu Ohno, writing in the Brookhaven Symposium on Biology in 1972 in the article "So Much ‘Junk DNA' in our Genome" is credited with originating the term. But his paper was focused "mainly on the fossilized genes, called pseudo genes, that are strewn like tombstones throughout our DNA. But as the term caught on in the 1980’s, its meaning was extended to "all non-coding sequences, the vast stretches of DNA that are not genes and do not produce proteins" (about 95% of the genome) [98.7% of human DNA - AJP]

[Francis Crick in 1954 (passed away in 2004 - his false "Central Dogma" ruled for over half a Century) - AJP]

[Francis Crick' 1956 original; unpublished but recognized by him; as well as Crick admitted in writing that at the time of declaring that protein to DNA and protein to RNA "never" happens "I did not appear to understand the correct use of the word dogma" (admission is in Crick's autobiography "What Mad Pursuit", 1988)]

This "Junk DNA" site represents the past, since upon retirement of Francis Collins from NIH (July 31, 2008) he admitted on video that "nobody talks about 'Junk DNA' anymore". Thus, the "Junk DNA" website represents an arduous struggle OF THE PAST HALF A CENTURY.

Eric Lander, Head of Broad Institute and member of the Presidents' Science Advisor Team, is also on record with their finding of over 1,600 long intergenic regions to play certainly "not junky" function.

The FUTURE is in "HoloGenomics" - after the "Principle of Recursive Genome Function" broke through the interlocking stalemate and enabled the "Holistic approach of integrating Genomics with Epigenomics in Informatics".

Those interested in the future, see HoloGenomics. Those looking back, see the "Table of Contents" linking to original articles and commented on the twists and turns of the struggle. - AJP

By: Leslie Pray, Ph.D. © 2008 Nature Education
Scitable
Nature Education
Citation: Pray, L. Transposons, or jumping genes: Not junk DNA? Nature Education 1(1), (2008)

Update: On February 25, 2009, the YouTube shown below was uploaded - introducing the next, "Genome Based Generation" that will make "Genome Based Economy" happen. After 3 or so weeks, the cameo was viewed 37,000 times, which shows a universal appeal and acceptance.

Most significantly, the two obsolete axioms of Genomics (as we used to know it), "The Central Dogma of Molecular Biology" (Crick, 1956) and the "Junk DNA" scientific misunderstanding (Ohno, 1972) are swept aside. An era is gone (minus a handful of morons).

The 21st Century "Genome Based Generation" throws old papers away at their 7th second of the cameo, when the first script appears. Proteins recursing to the DNA to regulate genome function used to be, for half a Century something that "never happens" (Crick, 1956; "The Central Dogma of Molecular Biology"). A paper on June 14, 2008 and a Google Tech YouTube on October 30, 2008 blew not one, but two "obsolete axioms" away. The above script takes it for granted that from a DNA > RNA > Proteins there is a recursion to DNA "regulatin' genes". Bye-bye, "Central Dogma"...

After only 1:20 (less than one and a half minutes...) the "Junk DNA" myth is destroyed by the pop-cult: "On that non-coding region" (formerly, "Junk") "you might get to regulate a gene". Bye-bye "Junk DNA".

An entirely new generation appeared, throwing away the old books - and making the "Genome Based Economy" happen...

Genome regulation is obviously the key. Regulation is impossible without a "feedback", which was forbidden by the Central Dogma - and even if there were those who suspected the "validity" of a Dogma, were strongly discouraged to look in what was scientifically argued (based on invalid premises) that the non-coding regions were "Junk". With the two show-stoppers removed, now there is The Principle of Recursive Genome Function. And that is the easy part. FractoGene laid down what kind of recursion is an algorithmic (software enabling) approach: a fractal, iterative recursion, to govern development of fractal organelles, organs and organisms by fractal DNA. With the full human personal genome becoming available with an affordable price tag, soon we'll search out fast enough, by means of Personal Genome Computers, what fractal defects (statistically significantly associated by health-conditions) might be found, how via epigenomic channels they could be mitigated, thus adverse conditions prevented or delayed, ultimately cured for patients, would-be patients (partners in prevention), than how personalized drugs, food-additives, foods, cosmetics, chemicals, materials and environments (etc) could be best matched to our genome.

It will take not only Silicon Valley, but a global economy, creating new jobs, new industries - and a healthier and happier new generation.