From: (Thanasis Argiriou) Sender: (Yaneer Bar-Yam) To: complex-science Date: Thu, 17 Jul 2008 11:28:55 -0400 Message-ID: X-Original-Return-Path: Received: from an-out-0708.google.com ([209.85.132.248] verified) by necsi.org (CommuniGate Pro SMTP 4.0.6) with ESMTP id 22128736 for complex-science@necsi.org; Thu, 10 Jul 2008 02:01:22 -0400 Received: by an-out-0708.google.com with SMTP id d31so610868and.92 for ; Wed, 09 Jul 2008 23:01:21 -0700 (PDT) DKIM-Signature: v=1; a=rsa-sha256; c=relaxed/relaxed; d=gmail.com; s=gamma; h=domainkey-signature:received:received:message-id:date:from:to :subject:in-reply-to:mime-version:content-type:references; bh=uvCAhjXxZXP464l6iGsYfNVczN+9wtIfJl8KB4zGIPA=; b=ZKiDbNEaVDUmzjWSOGJOoF+BYs1rOyDcJ3VRwgrxQRWQXPcgKanzSBK+q9k2zjp9WG sNZNb+/gE3VDFSJq1YeTs+A5RwN1j7G9rWMEOTPXg/fnu4XstpfPLHvAGrT6yRB0KEjC xtq+Z7vtsJY9SHSFLLTSPauJcSWw69XaDM0wk= DomainKey-Signature: a=rsa-sha1; c=nofws; d=gmail.com; s=gamma; h=message-id:date:from:to:subject:in-reply-to:mime-version :content-type:references; b=DrNxl7TiEDCxyi0S6F/4pi+PhprtVvbMkpoUBqYBtegUi3xqJXVqHR2rosGC4W1LPH dfwSJdClxYshgN4q6cekEGQ22NgU6mbK969KY9STQb8fZB3tWuG5d2OE/1o0HdTlr+xz EAqel3EL/3H0m4so/jhbXUVWjYo4rhvBSw2Ms= Received: by 10.100.134.10 with SMTP id h10mr7263451and.80.1215669681446; Wed, 09 Jul 2008 23:01:21 -0700 (PDT) Received: by 10.100.33.2 with HTTP; Wed, 9 Jul 2008 23:01:21 -0700 (PDT) X-Original-Message-ID: <79285ab50807092301l7217aaf1wd40f343897f9d801@mail.gmail.com> X-Original-Date: Thu, 10 Jul 2008 09:01:21 +0300 X-Original-To: complex-science@necsi.org Subject: Re: What is a gene? A dynamic & triadic definition of a gene In-Reply-To: MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_Part_20101_17440614.1215669681432" References: ------=_Part_20101_17440614.1215669681432 Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline Thanks for the info, though the question for me still remains open, Thanasis 2008/7/10 : > (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. > > > -------------------------------------------------- > For information about this discussion group visit > http://necsi.org/discuss/discuss.html > ------=_Part_20101_17440614.1215669681432 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline
Thanks for the info, though the question for me still remains open,
 
Thanasis

2008/7/10 <complex-science@necsi.org>:
(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.


--------------------------------------------------
For information about this discussion group visit
http://necsi.org/discuss/discuss.html

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