From: (JohnM) Sender: (Yaneer Bar-Yam) To: complex-science Date: Thu, 17 Jul 2008 11:28:55 -0400 Message-ID: X-Original-Return-Path: Received: from smtp110.sbc.mail.re2.yahoo.com ([68.142.229.95] verified) by necsi.org (CommuniGate Pro SMTP 4.0.6) with SMTP id 22129309 for complex-science@necsi.org; Thu, 10 Jul 2008 12:15:06 -0400 Received: (qmail 81833 invoked from network); 10 Jul 2008 16:15:05 -0000 DomainKey-Signature: a=rsa-sha1; q=dns; c=nofws; s=s1024; d=prodigy.net; h=Received:X-YMail-OSG:X-Yahoo-Newman-Property:Message-ID:Reply-To:From:To:References:Subject:Date:MIME-Version:Content-Type:X-Priority:X-MSMail-Priority:X-Mailer:X-MimeOLE; b=jFrASKnM3qPBFACMxD6gmpLhRyyBkKI58nhuFGHSlirpkSzgbJrt+US1IRWjUFEJgNyFtTqlYxl/MYYqmRYKW6DEyueikuL0bwA3veD5vZuoKQTlRzxGwHOpYz5fPlCKpD/0jTmBzaiC9OgKmg8LvwAKxVOPaVPLef/ruTLLzxA= ; Received: from unknown (HELO JohnCompaq) (jamikes@prodigy.net@12.75.196.209 with login) by smtp110.sbc.mail.re2.yahoo.com with SMTP; 10 Jul 2008 16:14:57 -0000 X-YMail-OSG: VkAnhucVM1m1lj_nsPElRkRLop5e6XNkJvuFq539K3MHYgWA6lz6rXxhqH_W.YoEC4bCKHPjpExRTkfWJVrKYRmTJc6GFUNDJSGYQPXuh9uKzafDmDDvNhQqwHYCYmgHRh_AMP8m7TMaHuvxB69KB6RM X-Yahoo-Newman-Property: ymail-3 X-Original-Message-ID: <006701c8e2a8$13dbe3a0$d1c44b0c@JohnCompaq> Reply-To: "JohnM" X-Original-To: References: Subject: Re: What is a gene? A dynamic & triadic definition of a gene X-Original-Date: Thu, 10 Jul 2008 11:59:49 -0400 MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_NextPart_000_003B_01C8E284.7494D310" X-Priority: 3 X-MSMail-Priority: Normal X-Mailer: Microsoft Outlook Express 6.00.2900.3138 X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_003B_01C8E284.7494D310 Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable 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). =20 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?=20 2. If there is 'mechanically' stored energy in the (unassigned?) DNA = stretches, is such energy capable of being put to use from DEAD tissue? = (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 -----=20 From: sji=20 To: complex-science@necsi.org=20 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=20 "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 ------=_NextPart_000_003B_01C8E284.7494D310 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable
Sung,
your post is commendable, an advanced treatise to extend the = narrowness of=20 the limited model-view even in the 'more advanced' version of the = obsolete views=20 (definitions).
 
As usual: I have 2 questions.
 
1. Isn't there a chance for a 'reversed' Prigogine effect: to=20 'assipate'(!!) factors INTO the process from the ambience, maybe at = least=20 not not yet recognised, or even discovered?
 
2. If there is 'mechanically' stored energy in the=20 (unassigned?) DNA stretches, is such energy capable of being put to = use from DEAD tissue? (I think of some answers: "dead" may mean = that it=20 lost such capability together with other transformations, the other is = the fact=20 that transplantations are feasible. I may be lay-wrong.)
 
Respects
 
John M
----- Original Message -----
From:=20 sji
Sent: Wednesday, July 09, 2008 = 11:54=20 PM
Subject: What is a gene? A = dynamic &=20 triadic definition of a gene

(Yaneer, if it is not too late, please replace my = previous post=20 with this
one.  Thanks.  Sung)

The most widely = accepted=20 definition of a gene during the past four decades
has been a = stretch of DNA=20 that codes for a protein. Although this simple
definition of a gene = served=20 well for the 20th-century molecular biology
and genetics, the new = data that=20 have been emerging since the mid-1990's
(when DNA microarrays were=20 invented) have made the protein-centered
definition of a gene = obsolete=20 [1,2,3]. A new definition proposed by
Gerstein and his coworkers at = Yale=20 now includes as a gene those DNA
regions that code for RNA as well=20 [2]:

     "A gene is a union of genomic = sequences=20 encoding a
      coherent set of = potentially=20 overlapping functional
     =20 = products."          &nb= sp;           &nbs= p;            = ;       =20 . . . . . (1)

The important phrase here is "functional = products", by=20 which the authors
mean proteins and RNA molecules that are = biologically=20 active.

The new definition of a gene given in (1) was motivated = by the=20 recent
unexpected finding [1,3] that a large portion of the human = genome=20 (about
30% of the DNA mass), although not coding for any proteins,=20 nevertheless
code for RNA molecules whose functions have not yet = all been=20 characterized.

There are two aspects to the definition of a = gene given=20 in (1) that I
believe require revisions:

  i)  It = is too=20 static, being based solely on gene "products", i.e.,
proteins and = RNA,=20 which are "equilibrium structures".  According to
Prigogine=20 (917-2003)[4], there are two fundamental classes of
structures in = nature --=20 equilibrium (e.g., rocks, chairs, DNA double
helix, nucleotide or = amino=20 acid sequences) and dissipative structures
(e.g., the flame of a = candle,=20 all sorts of gradients, action potentials,
gene expression = profiles). One=20 convenient way to distinguish dissipative
structures from = equilibrium=20 structures is to remember that, when energy
input is stopped, the = former=20 disappears but the latter remains.
For example, when a computer is = turned=20 off, the primary memory (a
dissipative structure) in CPU disappears = but the=20 secondary memory (an
equilibrium structure) in the hard disk=20 remains.

  ii) It excludes those DNA regions that regulate = gene=20 expression (called
promoters, enhancers, silencers, etc.) without = producing=20 any proteins or
RNA. In other words, Gerstein et al's definition of = a gene=20 excludes
"dissipative structures" which would include all = regulatory=20 processes in
the living cell. This is what Gerstein et al state=20 [2]:

   "Although regulatory regions are important = for=20 gene
    expression, we suggest that they should not = be
    considered in deciding whether multiple=20 products
    belong to the same gene. . . .=20 "      . . . . . . . . . . .  = (2)

To=20 remedy these perceived shortcomings, I suggest that the concept=20 of
"dissipative structures" [4] be incorporated into the definition = of a=20 gene
itself. One way to do this is as = follows:

    "A=20 gene is a DISSIPATIVE STRUCTURE that embodies = (or
    =20 stores) not only genetic information (in the form of=20 a
     nucleotide sequence of DNA regions) but = also=20 mechanical
     energy (in the form of = conformationally=20 strained DNA
     regions) generated from = chemical=20 reactions catalyzed
     by=20 enzymes."           = . . . .=20 . . . . . . . . . . . . . . . (3)

The fact that active regions = of DNA=20 carry mechanical energy, for example,
in the form of DNA = supercoils, has=20 been well established [5].  Such
mechanical energy stored in = DNA has=20 been variously referred to as
conformons [6] and "Stress-Induced = Duplex=20 Destabilizations" or SIDDS [5].

The definition of a gene given = in (3)=20 is tantamount to postulating that a
gene is a molecular machine = composed of=20 DNA segments and associated
proteins that stores mechanical energy=20 generated from chemical reactions
and uses this energy to = transcribe its=20 sequence information into RNA
molecules whenever and wherever = needed in the=20 cell for a right duration of
time.

The definition of a gene = given by=20 (1) can be made compatible with the
definition given by (3) if we = make the=20 following two postulates:

      "The = whole DNA=20 carries three kinds of genes -- = p-genes
     =20 coding for proteins, r-genes coding for RNA,=20 and
      d-genes coding for DNA = molecules." =20 . . . . . . (4)

The existence of d-genes is self-evident, since = DNA=20 serves as the template
for its own replication and this ability of = DNA is=20 heritable from one cell
generation to the=20 next.

      "DNA carries not only=20 genetic/sequence information = but
       also=20 the mechanical energy (called conformons or=20 SIDDS)
       to power gene=20 expression.       . . . . . . . . . . . = . .=20 .  (5)

In other words, by combining the dissipative = structure=20 concept of
Prigogine [4] and the conformon concept introduced in = molecular=20 biology
more than three decades ago (reviewed in [6]), a new = definition of=20 a gene
can be
formulated in two parts as=20 follows:

    i) "DNA carries three kinds of = genes, each=20 coding
       for proteins (p-genes), = RNA=20 molecules (r-genes),
       and DNA = molecules=20 (d-genes)." . . . . . . . . . . . . . . . .(6)

   ii) = "DNA=20 stores mechanical energy in the form=20 of
        conformons or SIDDS = that=20 powers the
        = spatiotemporally=20 organized motions of = chromatins
       =20 in order to express p-, r- and d-genes=20 in
        response to the = signals=20 received from the
       =20 = cytosol."          &nbs= p;            = ;      =20 . . . . . . . . . . . (7)

Statement (6) can be regarded as a = definition=20 of terms that are compatible
with facts, and what is original in = the=20 proposed 'triadic' definition of a
gene is contained in Statement = (7) in=20 the concept of conformons [6] or
SIDDS [5]. Conformons are defined = as the=20 sequence-specific conformational
strains of biopolymers that carry = 'ordered=20 energy' to power goal-directed
molecular motions [6].  The = first=20 direct experimental evidence for
conformons in DNA was provided by = DNA=20 supercoils [5] and for conformons in
proteins by the = single-molecule=20 measurements of myosin motions along actin
filament [7]. Also, = Statement=20 (6) deals with the informational aspects of
a gene, while Statement = (7) is=20 concerned primarily with the energetic
aspect of a gene, consistent = with=20 the information-energy complementarity
principle believed to = underlie all=20 self-orgnaizng processes in nature [8].

With all the=20 = best.

Sung

___________________________________________
S= ungchul=20 Ji, Ph.D.
Department of Pharmacology and Toxicology
Rutgers=20 University
Piscataway, N.J., = 08855


References:
  =20 [1] Pearson, H. (20056). Genetics: What is a gene? Nature=20 441:398-401.
   [2] Gerstein, M. B. et al. (2007). What = is a=20 gene, post-ENCODE? History
and updated definition. Genome Research=20 17:669-681.
   [3] Greally, J. M. (2007). Genomics: = Encyclopedia=20 of human DNA. Nature
447: 782-783.
   [4] Prigogine, = I.=20 (1977).  Dissipative Structures and Biological = Order.
 Adv. Biol.=20 Med. Phys. 16:99-113.
   [5] Benham, C. J. (1996). Duplex = Destabilization in Supercoiled DNA is
Predicted to Occur at = Specific=20 Transcriptional Regulatory Regions.  J.
Mol. Biol.=20 255:425-434.
   [6] Ji, S. (2000).  Free energy and=20 information content of Conformons
in proteins and DNA. BioSystems = 54:=20 107-130.
   [7] Ishijima, A., Kojima, H., Higuchi, H., = Harada,=20 Y., Funatsu, T. and
Yanagida, T. (1998).  Simultaneous = measurement of=20 chemical and
mechanical reaction.  Cell = 70:161-171.
  =20 [8] Ji, S. (2002). The Bhopalator: An Information/Energy Dual Model = of
the=20 Living Cell (II). Fundamenta Informaticae 49(1-3),=20 = 147-165.


--------------------------------------------------For=20 information about this discussion group visit
http://necsi.org/discuss/d= iscuss.html ------=_NextPart_000_003B_01C8E284.7494D310--