----- Original Message -----

From: Sungchul Ji

To: complex-science@necsi.org

Sent: Wednesday, August 06, 2008 12:02 AM

Subject: Re: What is a gene? A dynamic & triadic definition of a gene

John,

Thanks for your comments.

> Sung,
> your post is commendable, an advanced treatise to extend the narrowness of
> the limited model-view even in the 'more advanced' version of the obsolete
> views (definitions).
>
> As usual: I have 2 questions.
>
> 1. Isn't there a chance for a 'reversed' Prigogine effect: to
> 'assipate'(!!) factors INTO the process from the ambience, maybe at least
> not not yet recognised, or even discovered?

Are you referring to the opposite of "dissipate"?  Perhaps plant leaves
can be said to "assipate" free energy through their photosynthesis.
Leaves are open systems, and they must receive more free energy from its
environment than dissipate free energy into its environment, so that they
can store free energy in the form of carbohydrates.

Since every term must have its antonym, "dissipate" must also, and
"assipate" sounds to me like a good candidate.

>
> 2. If there is 'mechanically' stored energy in the (unassigned?) DNA
> stretches, is such energy capable of being put to use from DEAD tissue?

DEAD or ALIVE do not apply to molecules in my opinion, because the
smallest living entity is the cell.  So a cell can be living or dead, but
the molecular compoents of a cell are neither alive nor dead, regardless
of whether or not they are a part of a living cell or dead cell.

There are experimental evidence that the mechanical energy stored in DNA
molecules play an important role in gene expression, especillay in
chromatin remodeling (i.e., the opening or closing of chromatin segments
to expose the appropriate DNA sequences for transcription or replication
as required by the need of the cell). There are many ATP-dependent
chromatin remodeling enzymes that have been discovered during the past
decade or so.  One article lists 49 of them [A. Traverse and T.
Owen-Hughes, "Nucleosome remodeling", in: Chromatin Strcutre amnd
Dynamics: State-of-the-Art (J. Zlatanova and S. H. Leuba, eds., Elsevier,
2004, pp. 421-465].


(I
> think of some answers: "dead" may mean that it lost such capability
> together with other transformations, the other is the fact that
> transplantations are feasible. I may be lay-wrong.)
>
> Respects
>
> John M
>   ----- Original Message -----
>   From: sji
>   To: complex-science@necsi.org
>   Sent: Wednesday, July 09, 2008 11:54 PM
>   Subject: What is a gene? A dynamic & triadic definition of a gene
>
>
>   (Yaneer, if it is not too late, please replace my previous post with
> this
>   one.  Thanks.  Sung)
>
>   The most widely accepted definition of a gene during the past four
> decades
>   has been a stretch of DNA that codes for a protein. Although this simple
>   definition of a gene served well for the 20th-century molecular biology
>   and genetics, the new data that have been emerging since the mid-1990's
>   (when DNA microarrays were invented) have made the protein-centered
>   definition of a gene obsolete [1,2,3]. A new definition proposed by
>   Gerstein and his coworkers at Yale now includes as a gene those DNA
>   regions that code for RNA as well [2]:
>
>        "A gene is a union of genomic sequences encoding a
>         coherent set of potentially overlapping functional
>         products."                                           . . . . . (1)
>
>   The important phrase here is "functional products", by which the authors
>   mean proteins and RNA molecules that are biologically active.
>
>   The new definition of a gene given in (1) was motivated by the recent
>   unexpected finding [1,3] that a large portion of the human genome (about
>   30% of the DNA mass), although not coding for any proteins, nevertheless
>   code for RNA molecules whose functions have not yet all been
> characterized.
>
>   There are two aspects to the definition of a gene given in (1) that I
>   believe require revisions:
>
>     i)  It is too static, being based solely on gene "products", i.e.,
>   proteins and RNA, which are "equilibrium structures".  According to
>   Prigogine (917-2003)[4], there are two fundamental classes of
>   structures in nature -- equilibrium (e.g., rocks, chairs, DNA double
>   helix, nucleotide or amino acid sequences) and dissipative structures
>   (e.g., the flame of a candle, all sorts of gradients, action potentials,
>   gene expression profiles). One convenient way to distinguish dissipative
>   structures from equilibrium structures is to remember that, when energy
>   input is stopped, the former disappears but the latter remains.
>   For example, when a computer is turned off, the primary memory (a
>   dissipative structure) in CPU disappears but the secondary memory (an
>   equilibrium structure) in the hard disk remains.
>
>     ii) It excludes those DNA regions that regulate gene expression
> (called
>   promoters, enhancers, silencers, etc.) without producing any proteins or
>   RNA. In other words, Gerstein et al's definition of a gene excludes
>   "dissipative structures" which would include all regulatory processes in
>   the living cell. This is what Gerstein et al state [2]:
>
>      "Although regulatory regions are important for gene
>       expression, we suggest that they should not be
>       considered in deciding whether multiple products
>       belong to the same gene. . . . "      . . . . . . . . . . .  (2)
>
>   To remedy these perceived shortcomings, I suggest that the concept of
>   "dissipative structures" [4] be incorporated into the definition of a
> gene
>   itself. One way to do this is as follows:
>
>       "A gene is a DISSIPATIVE STRUCTURE that embodies (or
>        stores) not only genetic information (in the form of a
>        nucleotide sequence of DNA regions) but also mechanical
>        energy (in the form of conformationally strained DNA
>        regions) generated from chemical reactions catalyzed
>        by enzymes."           . . . . . . . . . . . . . . . . . . . (3)
>
>   The fact that active regions of DNA carry mechanical energy, for
> example,
>   in the form of DNA supercoils, has been well established [5].  Such
>   mechanical energy stored in DNA has been variously referred to as
>   conformons [6] and "Stress-Induced Duplex Destabilizations" or SIDDS
> [5].
>
>   The definition of a gene given in (3) is tantamount to postulating that
> a
>   gene is a molecular machine composed of DNA segments and associated
>   proteins that stores mechanical energy generated from chemical reactions
>   and uses this energy to transcribe its sequence information into RNA
>   molecules whenever and wherever needed in the cell for a right duration
> of
>   time.
>
>   The definition of a gene given by (1) can be made compatible with the
>   definition given by (3) if we make the following two postulates:
>
>         "The whole DNA carries three kinds of genes -- p-genes
>         coding for proteins, r-genes coding for RNA, and
>         d-genes coding for DNA molecules."  . . . . . . (4)
>
>   The existence of d-genes is self-evident, since DNA serves as the
> template
>   for its own replication and this ability of DNA is heritable from one
> cell
>   generation to the next.
>
>         "DNA carries not only genetic/sequence information but
>          also the mechanical energy (called conformons or SIDDS)
>          to power gene expression.       . . . . . . . . . . . . . .  (5)
>
>   In other words, by combining the dissipative structure concept of
>   Prigogine [4] and the conformon concept introduced in molecular biology
>   more than three decades ago (reviewed in [6]), a new definition of a
> gene
>   can be
>   formulated in two parts as follows:
>
>       i) "DNA carries three kinds of genes, each coding
>          for proteins (p-genes), RNA molecules (r-genes),
>          and DNA molecules (d-genes)." . . . . . . . . . . . . . . . .(6)
>
>      ii) "DNA stores mechanical energy in the form of
>           conformons or SIDDS that powers the
>           spatiotemporally organized motions of chromatins
>           in order to express p-, r- and d-genes in
>           response to the signals received from the
>           cytosol."                              . . . . . . . . . . . (7)
>
>   Statement (6) can be regarded as a definition of terms that are
> compatible
>   with facts, and what is original in the proposed 'triadic' definition of
> a
>   gene is contained in Statement (7) in the concept of conformons [6] or
>   SIDDS [5]. Conformons are defined as the sequence-specific
> conformational
>   strains of biopolymers that carry 'ordered energy' to power
> goal-directed
>   molecular motions [6].  The first direct experimental evidence for
>   conformons in DNA was provided by DNA supercoils [5] and for conformons
> in
>   proteins by the single-molecule measurements of myosin motions along
> actin
>   filament [7]. Also, Statement (6) deals with the informational aspects
> of
>   a gene, while Statement (7) is concerned primarily with the energetic
>   aspect of a gene, consistent with the information-energy complementarity
>   principle believed to underlie all self-orgnaizng processes in nature
> [8].
>
>   With all the best.
>
>   Sung
>
>   ___________________________________________
>   Sungchul Ji, Ph.D.
>   Department of Pharmacology and Toxicology
>   Rutgers University
>   Piscataway, N.J., 08855
>
>
>   References:
>      [1] Pearson, H. (20056). Genetics: What is a gene? Nature
> 441:398-401.
>      [2] Gerstein, M. B. et al. (2007). What is a gene, post-ENCODE?
> History
>   and updated definition. Genome Research 17:669-681.
>      [3] Greally, J. M. (2007). Genomics: Encyclopedia of human DNA.
> Nature
>   447: 782-783.
>      [4] Prigogine, I. (1977).  Dissipative Structures and Biological
> Order.
>    Adv. Biol. Med. Phys. 16:99-113.
>      [5] Benham, C. J. (1996). Duplex Destabilization in Supercoiled DNA
> is
>   Predicted to Occur at Specific Transcriptional Regulatory Regions.  J.
>   Mol. Biol. 255:425-434.
>      [6] Ji, S. (2000).  Free energy and information content of Conformons
>   in proteins and DNA. BioSystems 54: 107-130.
>      [7] Ishijima, A., Kojima, H., Higuchi, H., Harada, Y., Funatsu, T.
> and
>   Yanagida, T. (1998).  Simultaneous measurement of chemical and
>   mechanical reaction.  Cell 70:161-171.
>      [8] Ji, S. (2002). The Bhopalator: An Information/Energy Dual Model
> of
>   the Living Cell (II). Fundamenta Informaticae 49(1-3), 147-165.
>
>
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