From: (JohnM) Sender: (Yaneer Bar-Yam) To: complex-science Date: Wed, 06 Aug 2008 00:02:06 -0400 Message-ID: X-Original-Return-Path: Received: from smtp112.sbc.mail.re2.yahoo.com ([68.142.229.93] verified) by necsi.org (CommuniGate Pro SMTP 4.0.6) with SMTP id 22249822 for complex-science@necsi.org; Fri, 18 Jul 2008 15:51:07 -0400 Received: (qmail 47060 invoked from network); 18 Jul 2008 19:50:57 -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=jGDdJLKZEzqeo6ArTMqikg4S8PqJOoPBxDWzMkOxopyn4li5hln9mpb7d7Rsa87wkhLby7Yub7a2LpUmYH5N5yoeVHiVkdsP2tbNvp/nLlyqa7kFBERjmRvU3BSVbxbzJNjkG5NLMPYSZrtZiCd0AY/rJRdhD/hCzw6WnMWHQG4= ; Received: from unknown (HELO JohnCompaq) (jamikes@prodigy.net@12.75.199.73 with login) by smtp112.sbc.mail.re2.yahoo.com with SMTP; 18 Jul 2008 19:50:47 -0000 X-YMail-OSG: rSGlwscVM1nwQCUsuyq7fwDqnDlft0wd8bMa69clBZYQyspQxeyXExz8YSah84F1u.BdxVBNweiCidQW5tGglmH2IkCLRJl.pm8Q3Xc6LMzpbslPk0vThsderJfM.vsuTlU1JMnqJxRVqHKXnOIxlLMB X-Yahoo-Newman-Property: ymail-3 X-Original-Message-ID: <001a01c8e90f$8d60ed20$49c74b0c@JohnCompaq> Reply-To: "JohnM" X-Original-To: References: Subject: Re: What is a gene? A dynamic & triadic definition of a gene X-Original-Date: Fri, 18 Jul 2008 15:50:23 -0400 MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_NextPart_000_0017_01C8E8ED.FD1E1740" 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_0017_01C8E8ED.FD1E1740 Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Dear Thanasis - and mainly: Dear Sung. (A very professional addition to the topic by Sungchul Ji) Although it is somewhat unclear how to think about "LIFE", we have a = 'scientific' mechanism and 'identify' details within that.=20 In the picture - accepted in today's conventional biological sciences - = the DNA/RNA helical representation is instrumental. In such there are = those segments identified we call 'genes' (if this sentence is not too = primitive). As said they store energy (??), have multiple and connective = roles in building structures for the life process and are 'dissipative' = in Prigogine's terms. (I proposed the 'assipative' to be added, as the = input from that outside ambience inwards, just as the dissipative is = into it outwards).=20 Identifying in Gerstein et al's words (1) seems pretty meaningless by = itself and I go along with Sung's improvements (sort of). I find = "functional products" very unidentifying. (Does it include the synthesis = and process control of tooth enamel?)=20 I agree with Sung's critique on (2).=20 In Sung's (3) I would prefer - thinking of the post-Prigogine views of = total interconnection and interrelations - the word "relational" for the = one directional "dissipative". It is also poorly identifying, but allows = for later discoveries to be filled in.=20 I have my ignorance-based second thoughts in modeling 'memory' (any) = after the mechanical storage formats of our present and very primitive = computers. Also the tissue-conformational materialized memory theories = are suspect: they have a material-rigidity what the human memory lacks = and have to be 'recalled' (located) first before they can be 'recalled' = in an appropriate coding.=20 To (4)- (6 - 7): and who knows how many more - I mentioned the enamel = coding, may add other inorganicals (bone structuring etc. as i-gene?) = with all the complexity of a 'body building factory'. Our functional = inventory is by far not complete.=20 I want to express my appreciation for Sung's additions - in the right = direction - only propose to leave the way open for further discoveries = in that field - which is a pretty new one and IMO not necessarily with = the right connotations as of today, if we think in nature's totally = interconnected complexity, presently in its toddler level's views (if it = went that far at all).=20 I am not a professor, I can be (and am) vague, can propose halfway ready = ideas and leave the refutation or completion to those who understand the = domain better.=20 John Mikes ----- Original Mesage -----=20 From: Thanasis Argiriou=20 To: complex-science@necsi.org=20 Sent: Thursday, July 17, 2008 11:28 AM Subject: Re: What is a gene? A dynamic & triadic definition of a gene 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 ------=_NextPart_000_0017_01C8E8ED.FD1E1740 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable
Dear Thanasis - and mainly: Dear Sung.
(A very professional addition to the topic by Sungchul Ji)
 
Although it is somewhat unclear how to think about = "LIFE", we=20 have a 'scientific' mechanism and 'identify' details within that. =
In the picture - accepted in today's conventional biological = sciences - the=20 DNA/RNA helical representation is instrumental. In such there are those = segments=20 identified we call 'genes' (if this sentence is not too primitive). As = said they=20 store energy (??), have multiple and connective roles in building = structures for=20 the life process and are 'dissipative' in Prigogine's terms. (I proposed = the=20 'assipative' to be added, as the input from that outside ambience = inwards, just=20 as the dissipative is into it outwards).
 
Identifying in Gerstein et al's words (1) seems = pretty=20 meaningless by itself and I go along with Sung's improvements (sort of). = I find=20 "functional products" very unidentifying. (Does it include the synthesis = and=20 process control of tooth enamel?)
 
I agree with Sung's critique on (2).
In Sung's (3) I would prefer - thinking of the post-Prigogine views = of=20 total interconnection and interrelations - the word "relational" for the = one=20 directional "dissipative". It is also poorly identifying, but allows for = later=20 discoveries to be filled in.
 
I have my ignorance-based second thoughts in modeling 'memory' =  (any)=20 after the mechanical storage formats of our present and very = primitive=20 computers. Also the tissue-conformational materialized memory = theories are=20 suspect: they have a material-rigidity what the human memory lacks and = have to=20 be 'recalled' (located) first before they can be 'recalled' in an = appropriate=20 coding.
 
To (4)- (6 - 7): and who knows how many more - I mentioned the = enamel=20 coding, may add other inorganicals (bone structuring etc. = as i-gene?)=20 with all the complexity of a 'body building factory'. Our functional = inventory=20 is by far not complete.
 
I want to express my appreciation for Sung's = additions - in=20 the right direction - only propose to leave the way open for further = discoveries=20 in that field - which is a pretty new one and IMO not necessarily with = the right=20 connotations as of today, if we think in nature's totally =  interconnected=20 complexity, presently in its toddler level's views (if it went that far = at all).=20
 
I am not a professor, I can be (and am) vague, can = propose=20 halfway ready ideas and leave the refutation or completion to those who=20 understand the domain better.
 
John Mikes
 
 
----- Original Mesage -----
From:=20 Thanasis Argiriou
Sent: Thursday, July 17, 2008 = 11:28=20 AM
Subject: Re: What is a gene? A = dynamic=20 & triadic definition of a gene

Thanks for the info, though the question for me still remains = open,
 
Thanasis

2008/7/10 <complex-science@necsi.org&g= t;:
(Yaneer,=20 if it is not too late, please replace my previous post with = this
one.=20  Thanks.  Sung)

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

    "A gene is a union of genomic sequences = encoding=20 a
     coherent set of potentially overlapping=20 functional
     products."       =  =20                   =    =20             . . . . . (1)

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

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

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

 i)  It is too static, being based = solely on=20 gene "products", i.e.,
proteins and RNA, which are "equilibrium=20 structures".  According to
Prigogine (917-2003)[4], there = are two=20 fundamental classes of
structures in nature -- equilibrium (e.g., = rocks,=20 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=20 way to distinguish dissipative
structures from equilibrium = structures is=20 to remember that, when energy
input is stopped, the former = disappears but=20 the latter remains.
For example, when a computer is turned off, = the=20 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 any proteins or
RNA. In other words, Gerstein et al's=20 definition of a gene excludes
"dissipative structures" which = would=20 include all regulatory processes in
the living cell. This is what = Gerstein et al state [2]:

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

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

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

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

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

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

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

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

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

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

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

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

Statement (6) can be regarded = as a=20 definition of terms that are compatible
with facts, and what is = original=20 in the proposed 'triadic' definition of a
gene is contained in = Statement=20 (7) in the concept of conformons [6] or
SIDDS [5]. Conformons are = defined=20 as the sequence-specific conformational
strains of biopolymers = that carry=20 'ordered energy' to power goal-directed
molecular motions [6]. =  The=20 first direct experimental evidence for
conformons in DNA was = provided by=20 DNA 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)=20 is concerned primarily with the energetic
aspect of a gene, = consistent=20 with the information-energy complementarity
principle believed to = underlie all 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:
  [1]=20 Pearson, H. (20056). Genetics: What is a gene? Nature = 441:398-401.
 =20 [2] Gerstein, M. B. et al. (2007). What is a gene, post-ENCODE?=20 History
and updated definition. Genome Research = 17:669-681.
  [3]=20 Greally, J. M. (2007). Genomics: Encyclopedia of human DNA. = Nature
447:=20 782-783.
  [4] Prigogine, I. (1977).  Dissipative = Structures=20 and Biological Order.
 Adv. Biol. Med. Phys. = 16:99-113.
 =20 [5] Benham, C. J. (1996). Duplex Destabilization in Supercoiled DNA=20 is
Predicted to Occur at Specific Transcriptional Regulatory = Regions.=20  J.
Mol. Biol. 255:425-434.
  [6] Ji, S. (2000). =  Free=20 energy and information content of Conformons
in proteins and DNA. = BioSystems 54: 107-130.
  [7] Ishijima, A., Kojima, H., = Higuchi, H.,=20 Harada, Y., Funatsu, T. and
Yanagida, T. (1998). =  Simultaneous=20 measurement of chemical and
mechanical reaction.  Cell=20 70:161-171.
  [8] Ji, S. (2002). The Bhopalator: An=20 Information/Energy Dual Model of
the Living Cell (II). Fundamenta = Informaticae 49(1-3),=20 = 147-165.


--------------------------------------------------For=20 information about this discussion group visit
http://necsi.org/discuss/discuss.html

------=_NextPart_000_0017_01C8E8ED.FD1E1740--