Journal of Theoretical Biology 359 (2014) 192198

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Journal of Theoretical Biology

journal homepage: www.elsevier.com/locate/yjtbi

Two faces of entropy and information in biological systems

Yuriy Mitrokhin
The Institute of Problems of Chemical Physics of the Russian Academy of Sciences (RAS), 142432 Moscow region, Chernogolovka, Russian Federation

H I G H L I G H T S

Thermodynamic and information entropy are considered as two forms of total entropic process in biosystems.
The origination of complexity cannot be compensated only by thermodynamic entropy.
When and where in the past the entropy has been produced that is a payment for biological organization at present?
The idea is discussed that the genetic information is an instrument of entropy disproportioning in time.
The Second Low realization today cannot be without taking into account the information entropy in past generations.

art ic l e i nf o

a b s t r a c t

Article history:
Received 14 February 2014
Received in revised form
30 May 2014
Accepted 12 June 2014
Available online 20 June 2014

The article attempts to overcome the well-known paradox of contradictions between the emerging
biological organization and entropy production in biological systems. It is assumed that quality,
speculative correlation between entropy and antientropy processes taking place both in the past and
today in the metabolic and genetic cellular systems may be perfectly authorized for adequate description
of the evolution of biological organization. So far as thermodynamic entropy itself cannot compensate
for the high degree of organization which exists in the cell, we discuss the mode of conjunction of
positive entropy events (mutations) in the genetic systems of the past generations and the formation of
organized structures of current cells. We argue that only the information which is generated in the
conditions of the information entropy production (mutations and other genome reorganization) in
genetic systems of the past generations provides the physical conjunction of entropy and antientropy
processes separated from each other in time generations. It is readily apparent from the requirements of
the Second law of thermodynamics.
& 2014 Elsevier Ltd. All rights reserved.

Keywords:
Information entropy
Generating of new information
Disproportionation of entropy
Unsteadiness in genetic systems
Compensation for antientropic processes

1. Introduction
Discussion about implementation of the Second law of thermodynamics in living systems has always been a collision of diverse
points of view, especially when discussing the role of information
processes in such fundamental biological phenomena as growth,
embryogenesis, ontogenesis and evolution. The fact that genetic
information is correlated with the entropy production was
expressed in the question: "what is the entropy (and energy)
payment for information" (Romanovskiy et al., 1984).
Blumenfeld (1977) wrote: "According to the thermodynamic
criteria any biological system is not more ordered than a piece of
rock the same weight". However, a few lines later he admitted
formalism of his approach: "Orderliness of living matter and the
information it contained have a sense".
Prigogine and his school developed thermodynamics of
open nonequilibrium systems and formulated idea about the

E-mail address: ymitrokhin@mail.ru

http://dx.doi.org/10.1016/j.jtbi.2014.06.018
0022-5193/& 2014 Elsevier Ltd. All rights reserved.

nonequilibrium stationary state which these systems tend to.

It is characterized as a state with minimal and constant speed of
entropy production in the system. At the same time the total
entropy change (dS) for such open systems consists of deSthe
inow (outow) of entropy due to the exchange of matter and
energy between the system and the environment and diSthe
entropy production within the system: dS deS diS.
It should be emphasized that the minimum entropy production
is valid in close to equilibrium conditions. The authors extend the
theory to growth and development, emphasizing that the processes in biological systems do not contradict the second law of
thermodynamics. Ontogenesis is considered as a transition from
the less probable state to the more probable (Nicolis and
Prigogine, 1990). The last assertion hardly is justied. The more
probable state is disorganization, not organization. Organization
requires the prescriptive information to temporarily and locally
outsmart the Second law of thermodynamics of progressive,
relentless disorganization.
Interestingly, Prigogine and his colleagues speak exclusively
about the thermodynamic entropy in their works and avoid

Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

discussion of rather evident for every biologist fact that both in a

cell and multicellular organism there is a permanent creation of
new structures, maintenance of organization. All the pathos of
their works focuses on the emergence of structures in non
equilibrium dissipative systems which prepared articially as a
rule. It all is true without any doubt, and, apparently, the
contribution of this principleorganization out of chaoswas
decisive at the very early stages of the prebiotic evolution. But it
is not enough for adequate description of the modern biological
systems in terms of physical laws. The put forward by Prigogine
argument that the outow of the entropy of the system into the
environment deS can compensate for the production of entropy
within the system (diS) seems very unconvincing for real cells.
Hardly the outow of heat and low-molecular components (2,
2, etc.) from the cell, giving a contribution to the positive
entropy balance, is sufcient, especially since this outow is not
related to the creation of complex macromolecular structures in
the cell. Nonequilibrium structures of biopolymers are not dissipative, as their maintenance does not require any export of
entropy and they are conservative structures (Ebeling et al., 2001).
In the same vein other attempts to explain the spontaneous
generation of the organization in living organisms through the
continuous entropy production which accompanies the ow of
free energy through the system are made. However, doubts
remain. So, Klimontovich (1997) in his work, devoted to the
entropy production in open multilevel systems, answers to the
questioncan we expect that self-organization is the only result of
biological evolutionnot, as inner aspiration for self-organization
is not inherent property of physical and biological systems. He
supposes that since the state of full chaos, i.e. thermodynamic
equilibrium has not been determined (and is not characteristic of)
biological systems, and provided the absence of denition of full
order, the systems can be described in terms of chaos norm or a
relative degree of chaos. The concept more adequately describes
the state of genetic systems which are characterized by an
acceptable ratio between determinism and randomness (freedom)
for combining functional elements of the systems. It is seen that
when interpreting specicity of living objects the author considers
only thermodynamic entropy as a main factor dening the direction of their evolving.
The complexity of the correct interpretation of the efciency of
the Second Law of thermodynamics in biological systems continues to be relevant and sometimes elusive for understanding of
the problem. This is reected in the concluding sentences of the
problem analysis which was made by Rubin (2004): "In the center
of attention here is the main paradox that the increase in the
orderliness of biological systems is accompanied with a spontaneous production of positive entropy". An important step in
comprehending a specic role of biological information, its content and consideration for correct interpretation of the Second low
of thermodynamics was made by Quastler (1964) who dened two
principle moments for its generation: 1random selection of one
of possible versions, and 2memorization of such selection . Later
on, an essential condition was added, which consisted in that new
information can be generated in the unsteady-state systems only
(Chernavsky, 2001).
Among the present concepts of the essence of biological
information, two principal viewpoints can be distinguished: in
terms of physical reductionism, information is not considered as
really existing substance (Wachtershauser, 1997; Boniolo, 2003).
The opponents state that the thesis of physicalists about a
spontaneous polymerization of information macromolecules in
initial chemical (pre-biotic) systems is incorrect, that genes and
proteins have never been generated spontaneously. They were
synthesized by molecular machines, which physically combine
monomers to polymeric chains in accordance with information

193

matrixes and codes. Thus, proteins and genes are molecular

artifacts (Barbieri, 2012). We suppose that this statement opposes
cause to effect and violates the principle of holism. A disputable is
attribution of information to the class of physical essences, though
the author states that specicity of biological sequences cannot be
measured quantitatively. Therefore, it is not clearis information a
phenomenon of life or that of human consciousness. In other
words, does this concept reect objective reality or not?
An interesting information concept was proposed by Battail
(2009) who considers it as one of the main essences of the
physical world, along with the matter and energy. However, unlike
them, the information exists only in the world of living beings
where it can be generated and multiplied (where it can proliferate)
and may at the same time be annihilated (lost). The author
introduces the notion of potential information to denote the
information which exists in the form of some immaterial essence
in nonliving world. I the living world, potential information turns
into symbolic one through materialization into the form of the
base sequence of genomes. At the next stage of its passage it looks
as structural information of functional macromolecules and structures of cell metabolism . I can agree with the notion of potential
information, not in the prebiological world but rather in the world
of ideas that exist in the person's head. It is no mere chance
physicists nd not place for information in the strict system of
physical laws. One of such attempts was made in the well-known
works by Haken (1988) in the new interdisciplinary led called
synergetics. Using several model systems the author found the
appearance of information from observing the effects of ordering
or even self-organization. When the known one-stage order
emerges from chaos in laser or any other model system, it
resembles crystallization at a moment of attaining required
temperature rather than the appearance of organization.
The existence of special intangible essence in biological objects
was comprehended by Schredinger (1944) when 10 years prior to
the discovery of DNA structure he attributed mutation effects
transfer through generations with the effect of a certain nonphysical law .
Barbiery justly supposes that now genetic information should
be considered as new observable physical entity, which is present
in living objects along with other fundamental physical entities.
However, a more precise denition should be given. Information
and human consciousness as a derivative of information processes
in neuron networks appear as new non-physical realities emerging
parallel to the germination of life and becoming of human being.
They acquire sense only in the process of information transfer and
reception by a receiver, subsequent re-coding and generation of a
biological function or thought. The value of potential information
equals zero similarly to rest mass of elementary particles. We
suggest the following denition of the sense of information
for natural biological systems, namely, certain observed essence
consisting in a sequence of monomers of genetic macromolecules,
which provided carriers transfer to molecular recoding devices,
unambiguously realizes one of multiple possible sequences of elements when building functional molecules of another nature in a
genetic system. Probability of such event out of an organized biological system is close to zero even in the presence of messenger.
Thus, information is nonphysical essence, which arises inside a
pre-biological physico-chemical system at a stage of life origin,
evolves from generation to generation and is present in living
systems as long as they are such.
These denitions are have been made to show that information
is not coming to the system from without. It comes into existence,
becomes a reality in a primary physical-chemical system when the
succession of the following events spontaneously encloses to a
cycle: minimal polynucleotideprimary recoding devicepolypeptide showing presumably polymerase activityreplication of

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Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

parent polynucleotide (Eigen and Schuster, 1979; Eigen, 2000).

Essentially, all events of the primary information cycle and its
metabolic maintenance are possible in minimal volume limited by
a lipid membrane. Then the system can be reproduced due to
division and evolve by the Darwinian mechanism. Therefore,
it cannot be considered as a pure software as Chaitin, 2012 which
denes life as evolving software. The system evolves as a single
whole including all the above cycle elements. Any spontaneous
random changes in the primary nucleotide sequence are accompanied by changes followed in elements of the organized system
and, hence, are materials for selection.
Abel (2009) has recently justied the notion of "Prescriptive
information" (PI) whose main essence is prescription (instruction)
of the method of particular functions appearance in biological
systems. PI is an absolutely necessary working element contained
in the genome structure which ensures creation and support of
deterministic relations in the physical and chemical chaos of the
cell. The prescribed selection of the amine acid sequence in the
forming molecule of the enzyme or other functional agent determines the choice of the passageway of any metabolic chain (Abel
and Trevors, 2005; 2006). The idea of two forms of information
descriptive and prescriptive, as well as the idea about two forms of
entropy thermodynamic and informational, developed in this
article, are not connected with each other by content but reect
the complicated nature (duality) of the considered basic essences
information and entropy.
I would like to show in the article that PI arises not out of
information entropy (nothing may arise out of entropy) but thanks
to its existence. Information entropy, being the internal property
of genetic systems, violates the existing stable condition; this
results in the appearance of modied sequences in genomes
whose carriers will become objects of selection. In cognitive
semiosis, the appearance of PI is considerably reduced and even
not mandatory. Another image of semantic information, "Descriptive information", dominates here, which is typical for information
system of symbols on the basis of neuronal network of the higher
animals and human. But this is a subject for a separate article.
If in addition to the thermodynamic entropy in every cell we
consider coming in evolutionary time scale mutation process,
a peculiar another face of entropy which accompanies the occurring in the genetic material processes, the result is known to be a
violation of genetic programs and, as a consequence, deterioration
of cellular and organismic functions. Thus, information entropy as
if has no relation to the emergence of complexity, orderliness and
progressive evolution of biological systems. But, as it is shown
below, exactly this kind of entropy is the one responsible.
Thus, a conclusion can be drawn on that an obvious contradiction between continuous generation of entropy in a metabolic
system on one hand and the emerging biological organization on
other hand does not vanish. Apparently that is going on because in
the total entropy balance does not provide for information entropy
a motive force for mutational process in genetic systems in
course of their reproduction and functioning in generations.
Namely an acceptable part of information chaos, which exists in
real genetic systems, allows a random search for new combinations of informational elements of genome, which can be selected
for a new step of evolution. In effect, only separate authors, for
instance (Rubin, 2004), paid attention to the existence of this
paradox but did not try to interpret the mutation process in
genetic systems as the process of information entropy production
that should be taken into consideration to evaluate the general
entropy balance in the evolving biosphere.
In this article we try to correlate (ideally, of course) all the
known positive entropic processes which have taken place both in
the past and today in the metabolic and genetic cell systems, and
antientropy processes which include both the processes of

formation (origination) of the new elements of biological organization and the process of retention of existing ones, i.e. selected
and forming a functioning biological system elements. At the same
time it is intended that this correlation is lawful only if there is a
direct causal physical link between these two opposite classes of
processes, even if the mapped events spaced in time and space.
Real basis for giving a comprehensive biological sense to such a
correlation is a well-established fact of conjugated positive
entropy of biochemical transformations of substances of food with
high content of free energy and thermodynamically impossible
without such conjugating processes of formation of various
macroergic equivalents, synthesis of complex organic molecules,
biopolymers etc.
We consider that continuous mutation process in genetic
systems during the evolution is the process of information entropy
production. The resulting unsteadiness in the genetic information
system is a necessary condition for the generation of new
information. Transfer of gene complexes to the next generation
that is supported by the selection and provides better information,
is that causal physical link between the positive entropy events in
the past generations and antientropy processes in their descendants. In fact, this speculative correlation between entropy and
antientropy processes is that attempt to overcome the paradox of
contradictions between the emerging biological organization and
the growth of entropy. The problem is complex and cannot be
described by a simple formula.

2. Entropic processes in the system of metabolism

Having once begun, biological systems reproduce themselves
continuously and evolve, carrying a rather large but limited set of
standard chemical reactions, many of which cannot proceed
spontaneously and need to be conjugated with spending of free
energy and require the presence of catalysts formed in the same
system. During the evolution of living systems this set of chemical
reactions has become more complicated, and, apparently, long
time ago it has reached some reasonable limit and the degree of
perfection that provided the evolution of organisms, speciation
and stable existence of species for long periods of time over
3.5  109 years.
It is considered that on the metabolic level of living systems
there are spontaneous processes of all the biochemical transformations in conditions of minimum entropy production in the
system and its simultaneous substantive growth in the environment. In the system of conjugated biochemical transformations,
the processes of thermodynamically prohibited reactions are
provided by the fact that the part of the free food energy
irreversibly lost on the production of heat (i.e. entropy member
of balance) decreases, and the saved energy is used for positive
work in the construct process, for example, in any biosynthesis
reactions etc. The total balance of entropy production should be
positive. It is a requirement for the process. Thus, the process of
conjugated transformations becomes thermodynamically allowed
(Galimov, 2001; Opritov, 1999). In fact, here we are dealing with
underproduced entropy. And in this sense, the part of the free food
energy which could be dispersed for heat production is used for
creating "the organization" in the cell, i.e. the organization is
partially paid for by the underproduction of entropy.
Making these speculative qualitative estimations of the entropy
production balance on physicochemical level, we should always
remember that the conclusion of the spontaneity of biochemical
processes is something largely apparent. Indeed, thermodynamic
constraints are overcome through the mechanism of conjugated
positive entropy and antientropy reactions (if they are regarded
separately). However kinetic limitations are so great that they

Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

would be the same insurmountable barriers, if it were not for the

intervention of higher-level organization of the cell, if the system
did not have enzymes and other sophisticated infrastructure.
As being terminal links of an information transfer chain from
genes to effectors of proteins in a cell, ferments and other protein
structure realize the function of "guidance", direction of biochemical reactions in the cell. The term induced processes was
proposed by Zotin in order to distinguish them from verily
spontaneous (Zotin and Zotina, 1993).
Thus, in relation to the events of the metabolic level, the
positive balance of entropy production that accompanies biochemical transformations is not the only condition of these
processes. It is a necessary but not sufcient condition. Rethinking
Schredinger (1944) thesis that the organization is supported
removing the "orderliness" from the environment, today we can
say that the organization of living systems, orderliness, its structures, system maintenance in the stationary, far from equilibrium
condition with minimal entropy production is provided at the
expense of realization of genetic information contained in DNA.
As discussed here, the positive balance of the thermodynamic
entropy should be considered only "accounting" of the process,
but not the driving force. The author of the book devoted to
information and the theory of evolution wittily said: Life does not
use negentropy for food like the cat which licks sour cream
(Yockey, 2005). Indeed, the degree of orderliness of substances
entering the cell from the environment is not too high. They are
more carriers of free energy which can be freed, become accessible
for a cell and be used for the processes of thermodynamically
prohibited reactions. Both for the thermodynamic and information
entropy the main content of the concept is the internal inherent in
the system aspiration to the chaotization, the disruption of the
structure, the dispersion of part of the free energy in the form of
heat, i.e. in fact, the direction to the balance, to the more probable
state. And if, contrary to this system inner desire but conjugated
with it, opposite events occur, such as the complex biosynthesis,
the storage of available free energy in ATP, the biosynthesis of
macromolecules and, nally, the emergence of new information,
then, apparently, this process needs some additional driving force,
and manufactured in the system entropy is the only evidence of
owing process spontaneity. The driving factor in this process is
the genetic information.

3. Entropy and the genetic information

Consider another level of organization of living systems
(namely multicellular organism) in terms similar to those that
we used at the description of physiochemical intracellular processes. Leaving aside the physiochemical transformations of matter and energy in every cell, try to qualitatively evaluate the
directivity of the actual processes in the cell which we now regard
as the emergence of a new biological system (the organism).
It seems quite clear that exclusively the processes of developing
system structure complication, improvement and increase of an
organization degree take place during the entire period of full
organism formation (embryonic period). Following the terminology proposed by Schredinger (1944), during this process there is
a growth of the level of orderliness of elements composing the
system and only an entropy decrease are observed that is not
accompanied with its any parallel growth in the related parts of
the system. It must be remembered that we are talking only about
the events on the cellular level (in this case we do not consider
what happens in every cell). So, the formation of a multicellular
organism seems to be not accompanied with the entropy increase
about which we spoke above describing the metabolic processes
in cells; the impression is that at this level there is not some

195

inherent in the system potential which determines the spontaneous course of the process.
This logical impasse will be overcome, if we apply macromolecular or genetic level of biological systems, especially since all
the events of this level occur within the described system. The
causal connection between the events of these two levels is not
in doubt. Remaining within the limits of the natural science in
describing the phenomena and processes, we must, as before, in
the case of the description of intracellular physico-chemical
transformations, nd the force that determines the direction of
the spontaneously owing embryogenesis.
Without delving into details of embryogenesis we will try to
highlight this biological phenomenon from the point of view of
the requirements of the second law of thermodynamics. Positive
thermodynamic entropy balance in each cell of a multicellular
organism is not associated directly with the emerging and
growing organization, orderliness of this higher level in the
hierarchy of a multicellular organism. Obviously, without the
cells possessing of some properties which are necessary for the
formation of a multicellular organism, the embryo will not occur
and the result is just a larger number of cells, although each of
them has an obligatory positive entropy production balance.
Apparently, it is actually not the thermodynamic entropy produced in the cells of the developing embryo. It does not
determine the direction of the events of the considered hierarchy's level of living systems. The acquisition of certain properties that gives to dividing cells the ability to remain connected to
each other is apparently relevant to the implementation of the
new genetic information which originated in the evolving eukaryotic cellsthe predecessors of multicellular organisms. Its generating processed in genetic systems of these cells which possess
acceptable degrees of volatility and the possibility of mistakes
when replicating the nucleotide sequences of genes (Chernavsky,
2001). It was the rst and may be the most decisive step on the
path of the multicellular origination. Each of these countless
steps was an act of a new information birth.
The second, not less important event in the germ cells of
primary multicellular organisms was, obviously, origination in the
genomes of these cells of absolutely new, specic genes whose
activity modulated features of the hereditary cells phenotype in
such a way that in a growing embryo the cells with different
functional specicity began to originate. There is no doubt that
this became possible when the original genome of zygote was
enriched with a considerable set of genes new genes which did
not exist in free-living eukaryotic cells. The formation of a wide
spectrum of phenotypically different cellular elements in the
developing embryo was (and is) based on the same initial genome.
Eukaryotic cells have acquired an extremely useful evolutionary
innovation which allows them rational and sustainable use of the
resources of their actually large genome converting certain genes
in silence state or returning them in active one. We discussed it
more elaborately in the work (Mitrokhin, 2013).
The process of new genetic information generating is directly
conjugated with the changes of entropy (both thermodynamic and
information) but, however, it should be recognized that there is a
fundamental difference between the thermodynamic entropy and
the information one in probabilities of occurrence of elementary
events which make sense of each entropy type. The growth of the
thermodynamic entropy results in processes of biochemical transformations which are accompanied with the dispersion of part of
the free energy of the participants (presented in the system or
entering into it). The probability of elementary acts is very high
because the reactions of this type come with the release of energy.
Part of this energy is retained and will be then implemented for
the processes of thermodynamically improbable events, such as
the synthesis of universal macroergic compounds.

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Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

On the contrary, information entropy which we want to

characterize as a source of subsequent, related changes is the
result of very improbable events, because these events (mutations)
occur in macromolecular, highly organized systems which have
largely deterministic character of consecutive reactions process.
This kind of entropy in no way affects the physical orderliness of
the nucleotide sequences (only the semantic!) and, therefore, does
not contribute to the change of thermodynamic entropy of the
system (they are something like immiscible substances). Information entropy contributes to the implementation of the ranges of
freedom which are possessed by the carrying genetic information
nucleotide sequence. Time of waiting for occurrence of the
elementary entropy events of this kind signicantly (many times)
exceeds the time of the occurrence of such events for the
thermodynamic entropythe other face of entropy as a physical
phenomenon. Owing to this modest contribution to the overall
entropy balance which is the driving force of biological systems
evolution it becomes possible to overcome determinism of strict
sequence of DNA replication events and the generating of new
information motives.
Produced in a cell thermodynamic entropy compensates for the
reproduction of the physical component of the genetic information
systemchemistry and physics of structures which transfer and
implement information, i.e. compensates for current events of the
metabolic level but not the events of the evolutionary process.
Now we need to understand how the system became what it is;
we need to understand how it was complicated, acquired new
properties and how it progressively evolved. The possibility of
mistakes in nucleotide sequences during their reproduction
should be considered as implementation of the immanent aspiration of the information system to state of chaos and information
distortion, i.e. as the information entropy growth. One important
feature of every occurring in the genetic system entropy event
should be noted: it is remained in memory, in contrast to the
elementary thermodynamic events or, for example, the breakdown of proteins and more complicated cellular structures. These
kinds of mutation lead to nothing. They are forgotten. As a general
rule, they are not transferred to the next generation.
The situation is quite different with the fate of DNA mutations.
As positive entropy events (i.e.causing chaos, disorganization) in
relation to the information content of DNA sequence, mutations
practically do not have an impact on thermodynamic entropy
balance of this system. From this point of view, they have zero
cost. As a rule, they do not change the amount of the Shannon
information which, in principle, can be measured in known units.
They change the quality of the information, its content. In this
connection the information entropy in genetic systems is an
analog Shennon's concept of entropy in articial communicative
systems (Shannon, 1948). But in this systems the new information
is not be originated. It is come down only. Of course, we should not
forget about the energy spending on this new information that is
paid with the constantly going thermodynamic entropy production in the cells. Genetic system remains in memory everything
that has overcome replicative and drafting mechanisms which
save the original information. The true cost of new acquisitions
will be detected only after the selection performs its function.
In this context, it is permissible to focus somewhat passive role of
natural selection in the evolution of the genetic system. Real, active
creativity occurs in the information system the physical structure of
which allows it to combine its elements in periods of instability and
remain in memory detected variants. Everything that has been
changed in the genome after overcoming cellular repair mechanisms and correction remains in memory. The selection performs a
simply passive function, so to speak; and it occurs at later stages.
It eliminates nonviable organisms (phenotypes) with their altered
gene complexes and leaves viable ones (Brooks, 2000).

Common sense dictates that the selection selects neither the

best genes (Dawkins, 2006) nor the most successful populations
and species (Shcherbakov, 2005a, 2005b) a successful combination of genes is selected as the information subsystem of the whole,
i.e. cells (in the world of unicellular) or the organism (in the world
of multicellular). On the other hand, a successful combination of
genes which ensured this successful phenotype is not retained in
sexual reproduction of new generations and is not selected, so to
speak. But the genes included in it are retained, i.e. selected for the
following generations.
This approach to the concept of selection is consistent with
the concept of holism according to which the inheritance is
implemented not only by the transmission of genes, but it is
provided by a certain integrity of the composing the system
elements (Shcherbakov, 2012).
Information entropy which accompanies acts of information
transfer to the new generations has regularly contributed its share
to the general entropy expenditures required for maintaining of
the nonequilibrium state and falls on the scale which has a
positive sign (i.e. towards the equilibrium state). These rare
uctuations transfer the system in an unsteadiness state only for
a short time and it is accompanied with the birth of a new
information motive. The information entropy which accompanies
this simple event can in no way inuence the general entropy
balance in a separate cell. But it is summed with the whole array of
similar events on an evolutionary time scale and assures us that
the Second law of thermodynamics is adhered to. The system's
return in a stable state allows maintained a signicant nonequilibrium state characterized by high level of organization.
The memorization mentioned above is not a birth of new
information yet. It will become the same only when it is sent,
i.e. it will be reproduced in the new generation and will be
implemented in the form of any particular cell function and the
survival of this generation descendants will not worse than that of
the ancestors, maybe even better. It is possible only in systems
with three obligatory properties: metabolism, self-reproduction
and mutability, i.e. in living systems. Eygen and Shuster dened
these properties as "prerequisites for feasibility" in capable of
selective self-organization systems (1979). The birth of "organization out of chaos",the formula of expression of the new class of
physical phenomena,is possible exactly in these systems. Apparently, this formula was implemented at the earliest stages of
the information emergence - at the origin of life. However, in
the process of the new information emergence there were equally
the events the meaning of which is determinism and steadiness.
And here in the rst place is a unique structure of DNA which
provides long-term retention of genetic information by chemical
stability of the structure and the ability to enzymatic matrix selfreproduction. However, there is a possibility of new sequences as a
result of random errors in replication.
In addition, here we can talk about the genetically provided
evolution of the genome; it begins to be implemented in the more
complex genomes which have new genes whose products form an
apparatus that enhances the genetic instability and provides
advanced combinatorics of genetic material and the origination
of new genes (Carroll, 2002). Amazingly, this enzymatic apparatus
is not an independent structure performing function of mutability
increase, although the existence of such special evolutionarily
supported apparatus is postulated in some works (Radman,
1999; Earl and Deem, 2004) that is hardly justied. Shcherbakov
(2005a, 2005b) rightly noted that selection of the mutagenesis
high rate seems absurd. The mentioned above apparatus is an
integral part of replicative complex of genome and at the same
time the mechanism of recombinational DNA repair (Paques and
Haber, 1999. Both of structural-functional features of the genome
originated in it and were supported by the selection as they

Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

performed conserving function; they provided memory and accuracy of the genome duplication in generations (Shcherbakov,
2005a, 2005b; Rice and Chippindale, 2001). The primary nucleotide sequence is strictly retained but larger elements of the
genome (genes, complexes genes, promoters and other elements)
are shufed. Impressive recent achievements of comparative
genomics prove this observation. Deep conservatism of nucleotide
sequences of genes contrasts with higher mobile gene composition of genomes and, to higher extent, evolution instability of
genome architecture, i.e. arrangement of genes in genome
(Koonin, 2009, 2012; Novichkov et al., 2009; Koonin and Wolf,
2010). It provides (especially in gametogenesis) with the origination of new, unexpected genetic combinations. This process goes
in parallel with the regular (evolutionarily more primitive),
ancient mutagenesis at the level of single nucleotide substitutions.
At the stage of selection there is no any creativity about which,
for example, Ayala, 2007. There is either "applause" or "stunned
silence". The creativity took place on the scene of life when
emerged in genetic information system new information realized
in an unexpected turn of events in the cell, in the modied
phenotype. If we see natural selection only as its nal stage, i.e.
elimination of nonviable forms, and at the same time we are aware
of the fact that this process does not require the functioning of any
mechanisms and is implemented on its own, then we lose sight of
the two rst and the most important stages of Darwin's natural
selection that he dened as the nature of the organism. In other
words, a creative role is played not by the last stage of the whole
selection process, but by its rst phase evolving information
systems.

4. Concluding remarks
We observe in a living cell several parallel conjugated processes
the driving force of which is accompanying these processes
entropy in two forms: thermodynamic entropy and information
one. The processes of metabolism providing the formation of
necessary substrates and macroergic equivalents proceed due to
spontaneous oxidation of food substances which possess the free
energy and are accompanied with the production of a considerable
degree of thermodynamic entropy. This type of entropy compensates for those conjugated antientropic processes (such as muscle
contraction, active transport of substances, the biosynthesis of all
polymers etc.) that cannot proceed spontaneously.
Basic events of the metabolic level are sequence of physicochemical transformations of small molecules and determine the
system's aspiration system for the most probable statethermodynamic equilibrium. However, it does not occur for the reason
that the system is open for matter and energy and contains an
internal source of informationgenetic system of cells which is a
macromolecular complex and requires the constant reproduction
of its structure for current information cell maintenance and for
transfer of information to the future generation.
Process of operations on genetic material includes two essentially different components. The elementary acts of polymerization
of the predecessor monomers which possess a considerable
reserve of free energy ow spontaneously and are accompanied
with the production of thermodynamic entropy. The resulting
molecular orderliness (i.e. the process of polymerization) is evidence of the decrease of the entropy balance member which
reects its production within the system. This rst component of
the genetic system elements reproduction provides the formation
of its physical and chemical structure.
The second aspectits informational content, its specic
sequence which provides the functional organization of the
system is inherited to the newly synthesized descendant

197

molecules without spending of additional energy and without

change of thermodynamic entropy. This becomes possible owing
to matrix mechanism of complementary DNA duplication. This is
true both for the cell cycle process and for the process of a
multicellular organism reproduction (embryogenesis).
The mentioned above positive balance of thermodynamic
entropy production which accompanies and compensates for
occurring in the cell negative entropic processes is typical for
the periods of steady state of the system. The cell with the most
possible precision duplicates genetic material and transfers it to
the next generation.
Thus, the driving force of the entire set of processes in the cell
and in the multicellular organism in selected periods (i.e. periods
of ontogenesis) is continuously generating in them thermodynamic entropy. However, this positive entropy balance describes
only the energy side of intracellular processes in their steadiness
periods. This is a necessary but not sufcient for the process of
progressive evolution condition. The information component is
equally important and has its source of those rare events in genetic
systems of individual cells that we call mutations. Basically, this is
a demonstration of another face of entropy as a physical phenomenon; it is inherent in the system aspiration to the chaotization, to
the disruption of largely deterministically determined elementary
events in the genetic system. In those rare cases when internal
uctuations overcome sustainable condition of the genetic system,
in the genome emergence of new information motives occurs.
They are tested by the selection on the viability and can be
transmitted in a series of generations. Transfer of new genetic
information supported by the selection in the mode of steady state
of the system is fully compensated with the production of the
thermodynamic entropy in the process of energy maintenance of
macromolecules synthesis. However, the origination of these new
information motives in the genome of the cells and the following
implementation of the new organizational structure which was
not until then is perceived by the observer as a violation of the
entropy balance (apparent) that is especially evident, for example,
during embryogenesis. At this moment we forget about the
information entropy which found itself in all periods of the life's
evolution in the form of random uctuations in generating these
information motives.
We would like to discuss the idea that in living systems there is
the phenomenon of disproportionation of entropy in time. It should
be understood as a kind of conjugation of positive entropy events
in the genetic material of cells of past generations with the
formation of highly organized structures in modern organisms;
and this conjugation can be considered a way of implementation
of the Second law of thermodynamics in uninterrupted living
systems with a very long lifetime. Of course, we are aware of the
fact that the information entropy which was produced in the
genomes of past generations in no way can be taken to the entropy
balance of current cell. This would contradict the principle of
obligatory physical conjugation between two processes going on
in the thermodynamically opposite directions. The proposed term
"disproportionation of entropy in time" is intended to emphasize
that genetic information physically transmitted in generations was
created and improved during the evolution in really existing
genetic information systems which experience continuous entropy
pressure transforming these systems into an unstable state.
Darwinian selection in this process performed and still performs
a passive function,it only eliminates the whole vast array of
failed (nonviable) phenotypes and the corresponding with them
combinations of genes emerging as a result of mutagenesis
(Brooks, 2000). Nothing like that occurs with the thermodynamic
entropy. It is simple and clear: the implementation of each event
(for example, the synthesis of peptide bond) is achieved owing
to conjugate ongoing process of hydrolysis of ATP and is

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Y. Mitrokhin / Journal of Theoretical Biology 359 (2014) 192198

accompanied with a release of energy and entropy production

which is sufcient for the synthesis of this peptide bond. The next
amino acid needs new entropic spending. But it is impossible to
make a new protein molecule only at the expense of current
thermodynamic spending without presentation of information.
Feeling of elusive sense of the phenomenon is reproduced in
question rst articulated by Schredinger (1944): "In accordance
with which such a well-known physical law a random, chaotic
event of molecular level occurred, perhaps, 109 years ago in some
place of genome of that time, today determines the specic
phenotypic attribute which has macroscopic form and in some
cases we can measure it quantitatively. We may assume that living
matter obeys a new type of physical law. Or we should call it nonphysical". These sentences written 10 years before the discovery of
the DNA structure and formulation of ideas about genetic information are striking for its vision.
Thermodynamic entropy produced in cells is not enough to
compensate for all the processes which accompany the growth
and development, denitely antientropic processes, the processes of creation of organized biological structures. It is clear that
this entropy is only a constant replenishment, "the electric current
to a moving train". Transfer of information is essentially a way of
relating entropy and antientropy processes which we mentioned
in the introduction; it with a logical inevitability arises from the
requirements of the Second law of thermodynamics in accordance
with which the organization created in the organisms must be
compensated with an excess with the respective amount of
positive entropy. Poplavskiy arrays a relationship between entropy
and information in the following line: "Thermodynamics of
information processes explores the transformation of entropy into
information, and the last oneinto negentropy" (Poplavskiy, 1981).
Summing up, we note again that the two faces of entropy
correspond with two fundamentally different periods of biological
systems existence. Production of the thermodynamic entropy in
the metabolic system provides maintenance of steady state and
reproduction of already existing information. This is evolution
towards the most probable state in periods of ontogenesis.
Production of the information entropy in the genetic system
accompanies the transformation of a system into an unstable state
and is a condition for the generation of new information. These
events correspond with the evolution of the system to a less
probable state which is formed from the unlikely events (mutations) in the genetic information system, and it becomes possible
only with the participation of selection in the process of phylogenesis and memorization of the selected sequence (information
motives). Modern organization of the evolving biological system is
mainly payable in the payments, in a variety of past evolution
moments, in the acts of the birth of new information xed by the
selection. At that time there was also entropy productioninformation entropy which broke "the order" in those moments. Its
disproportionation in time, its today's accounting weaken the
tension caused by the existence of a paradoxical contradictions
between the evident increase of orderliness of living systems and
the production of positive entropy.
References
Abel, D.L., Trevors, J.T., 2005. Three subsets of sequence complexity and their
relevance to biopolymeric information. Theor. Biol. Med. Model 2 (29), 116.
Abel, D.L., Trevors, J.T., 2006. Self-organization vs. self-ordering in life-origin
models. Phys. Life Rev. 3, 211228.
Abel, D.L., 2009. The biosemiosis of prescriptive information. Semiotica 174, 119.

Ayala, F.J., 2007. Darwin's greatest discovery: design without designer. Proc. Natl.
Acad. Sci. USA 104, 85678573.
Barbieri, M., 2012. What is information? Biosemiotics 5, 147152.
Battail, G., 2009. Living versus inanimate: the information border. Biosemiotics 2
(3), 321341.
Blumenfeld, L.A., 1977. Problemy biologicheskoy ziki [Problems of Biological
Physics]. Nauka, oscow (in Russian).
Boniolo, G., 2003. Biology without information. Hist. Phil. Life Sci. 25, 255273.
Brooks, D.R., 2000. The nature of the organism life has a life of its own. Ann N.Y.
Acad. Sci. 901, 257265.
Carroll, R.L., 2002. Evolution of the capacity to evolve. J. Evol. Biol. 15, 911921.
Chaitin, G., 2012. Proving Darvin. Making Biology Mathematical. Pantheon Books,
New York p. 56.
Chernavsky, D.S., 2001. Sinergetika i informatsiya [synergetics and information].
Nauka, Moscow (in Russian).
Dawkins, R., 2006. The selsh Gene, 30th Anniversary Edn.. Oxford University Press,
Oxford.
Earl, D.J., Deem, M.W., 2004. Evolvability is a selective trait. Proc. Natl. Acad. Sci.
USA 101, 1153111536.
Ebeling, V., Engel, A., Feistel, R., 2001. Fizika protsessov evolyutsii [Physics of
Evolutionary Processes]. Editorial URSS, Moscow (in Russian).
Eigen, M., 2000. Natural selection: a phase transition? Biophys. Chem. 85, 101123.
Eigen, M., Schuster, P., 1979. The hypercycle. A Principle of Natural selfOrganization. Springer-Verlag, Berlin, Heidelberg, New York.
Galimov, E.M., 2001. Fenomen Zhizni. Mezhdu Ravnovesiem i Nelineynostyu
[Phenomenon of Life. Between Equilibrium and Nonlinearity]. Editorial URSS,
Moscow (in Russian).
Haken, H., 1988. Information and Self Organization, (Springer, Berlin, Heidelberg,
New York).
Klimontovich, Y.L., 1997. A criterion of relative degree of chaos or order for open
systems. BioSystems 42, 85102.
Koonin, E.V., 2009. Evolution of genomes architecture. Int. J. Biochem. Cell Biol. 41,
298306.
Koonin, E.V., Wolf, Y.I., 2010. Constraints and plasticity in genome and moleculargenome evolution. Nat. Rev. Genet. 11, 487498.
Koonin, E.V., 2012. Logic of Chance. The Nature and Origin of Biological Evolution.
Pearson Education, Inc, FT Press, USA.
Mitrokhin, Yu.I., 2013. The function of basic information systems for a new level
advance in biological organization. [Biology Bulletin Reviews], Usp. Sovr. Biol.
133 (2), 209222 (in Russian).
Nicolis, G., Prigogine, I., 1990. Poznanie slozhnogo [Exploring Complexity]. Mir,
Moscow, pp. 7580 (in Russian).
Novichkov, P.S., Wolf, Y.I., Dubchak, I., Koonin, E.V., 2009. Trends in prokaryotic
evolution revealed by comparison of closely related bacterial and archaeal
genomes. J. Bacteriol. 191, 6573.
Opritov, V.A., 1999. Entropy of biosystems. Soros Educ. J. 6, 3338 (in Russian).
Paques, F., Haber, J.E., 1999. Multiple pathways of recombination induced by
double-strand breaks in S. cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349404.
Poplavskiy, R.P., 1981. Termodinamika informatsionnyih protsessov [Thermodynamics of Information Processes]. Nauka, Moscow (in Russian).
Quastler, H., 1964. The Emergence Of Biological Organization. Yale University Press,
New Haven, London.
Radman, M., 1999. Mutation: enzymes of evolutionary change. Nature 401,
866869.
Rice, W.R., Chippindale, A.K., 2001. Sexual recombination and the power of natural
selection. Science 294, 555559.
Romanovskiy, Y.N., Stepanova, N.V., Chernavskii, D.S., 1984. Matematicheskaya
biozika [Mathematical Biophysics]. Nauka, Moscow, pp. 264272 (in Russian).
Rubin, A.B., 2004. Biozika. 1: teoreticheskaya biozika [Biophysics.: Theoretical
Biophysics], vol. 1. Nauka, Moscow: MSU (in Russian).
Shannon, C., 1948. A mathematical theory of communication. Bell. Syst. Tech. J.
II 3, 379423.
Schredinger, E., 1944. What is Life?. Cambridge University Press, Cambridge, UK.
Shcherbakov, V.P., 2005a. Evolyutsiya kak soprotivlenie entropii [Evolution as a
resistance to the entropy]. Zhur. Obsch. Biol. [Biol. Bull. Rev.] 66 (3), 195211 (in
Russian).
Shcherbakov, V.P., 2005b. Evolyutsiya kak soprotivlenie entropii [Evolution as a
resistance to the entropy]. Zhur. Obsch. Biol. [Biol. Bull. Rev.] 66 (4), 300309 (in
Russian).
Shcherbakov, V.P., 2012. Stasis is an inevitable consequence of every successful
evolution. Biosemiotics 5, 227245.
Wachtershauser, G., 1997. The origin of life and its methodological challenge.
J. Theor. Biol. 187, 483494.
Yockey, H.P., 2005. Information Theory, Evolution and The Origin of Life, U K.
Cambridge University Press, Cambridge.
Zotin, A.I., Zotina, R.S., 1993. Fenomenologicheskaya teoriya razvitiya, rosta I
stareniya organizma [Phenomenological Theory of Development, Growth and
Aging of the Organism]. Nauka, Moscow (in Russian).