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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.
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).
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?)
I agree with Sung's critique on (2).
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.
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.
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.
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).
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.
John Mikes
----- Original Mesage -----
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 < 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.
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