Late contribution to biol. info

Dear all,
As a member of the "Vienna group" around Wolfgang Hofkirchner at the Technical University,
 I want to mention some things concerning the notion of information in the context of molecular biology.

Epigenetic Networks: The Emergence of Cellular Information by Selforganization.

The enlightment of the structure of the DNA by James Watson and Francis Crick in 1953 lead to
 a consolidation of the reductionistic view of the gene as the basic central agent in biological information
 processing. The central Dogma of molecular biology formulated by F. Crick states that the information
 necessary for building up and maintaining life flows just in one direction, basically from the genotype
 (DNA) to the Proteins, which serve as structural and functional agents thus establishing a given Phenotype.

                 DNA > RNA > Proteine > Phenotype

Fig.1 Linear processing of genetic information within the dogma of molecular biology.

This few implements the following:
1) Information flows only in one direction that is from the genotype to the phenotype.
2) Environmental imbalances (within a non-lethal range) do not essentially affect the genotype.
3) Mutations altering a given genotype are only stochastic sensations.
4) A given phenotype can be understood by the knowledge of all its constituents and by the knowledge
 of the regulatory events how these constituents are build by translating the information encoded in the genes (DNA).

This DNA-focused view of mainstream molecular biology joins the notion of information exclusively to the
 genetic code. An enlargment of this DNA-focused view to a "theory of life" states that also complex behavior
 and lapse (e.g. Cancer) can solely be explained by the action of genes and their surrogates. This view does not
 consider the concerted action of multiple agents, when it is not possible to explain this actions in
 a linear-causal model.
This does not mean, that no linear interactions between elementsoccur in a cell, or that the scientists investigating
 such circumstances are on the wrong way, but I want to mention that such linear views are not sufficient to
explain biological information. So it is more the complex dynamic interaction of genes, proteins, metabolites
 and signals from the environment that serve to define and maintaine the behavior of a cell.
Therefore it is necessary to develop an "informationtheory of the cell" wich explains how a cell under given
 constrains develops special properties, which defines her function e.g. in a tissue, or enables the survival of
 a single (cellular) individual by adaptation to a given reality.
One approach to such a multilevel view of living entities emphasizes an additional, informational network
 within a cell, which integrates all the agents present to a highly organized informational state.
 This informational network is of epigenetic nature which emphasizes the fact that it exists besides and above
the allready well understood genetic network.

    _______________________________
    | | | |
DNA > RNA > Proteine > Epigenetic networks > Phenotype
                                                              |
                                                      Environment

Fig.2 Non-linear processing of cellular information mediated by epigenetic networks
. Flow of information occurs between all constituents. Also environmental parameters
contribute to the state of epigenetic networks.

The epigenetic networks, resemble the playground for selforganized phenomena, that give rise to
 an organisational control above the genome, generating and maintaining a specific developmental
 or terminal status of a cell.
(Epigenesis is a notion, allready used at the beginning of the 20th century by vitalistic biologists
 (Driesch, Roux) to explain gestalt-building processes during morphogenesis. They used epigenesis
 to designate a principle, similar to Aristotels entelechie, acting within every living entity.
This principle, so the vitalists generates form and gestalt.
A modern definition of epigenesis is given by Robin Holliday [1990, DNA methylation and
epigenetic inheritance. in: Phil. Trans. Royal Soc. Lond. B326: 329-338]:
"Classical genetics has revealed the mechanisms for the transmission of the genes from generation
 to generation, but the strategy of the genes in unfolding the developmental programme remains
 obscure. Epigenetics comprises the study of the mechanisms that impart temporal and spacial
 control on the activity of all those genes required for the development of a complex organism
 from the zygote to the adult. As such it establishes the basis for a level of organisational control
 above the genome; a level that is now well established in fact, but continues to evade decisive theoretical insight".

So there are two essential different informational systems in a cell:
(a) The processing of genetic information (as encoded by DNA) leads to the structural and functiona
l elements of a cell (linear processing by transcription, splicing, translation ...)
(b) The processing of epigenetic information (emerging as a cause of different parameters in a given
 compartment, such as certain proteins in defined quantities, metabolites and signals obtained
 from the environment) leads to the coordination of all agents and enables an integrated behavior of the cell.
Epigenetic networks generate self-organized patterns which constitute the cellular information
 (remind Benard-Cells, Belousov-Zhabotinsky-Reaktion or the life-cycle of Dictyostelium discoideum).
"Gene silencing", "Genomic imprinting", "Transposition" and "Paramutation" are today well known
epigenetic mechanisms, which alter the cellular information without altering the genetic information.
 But about the cause of epigenetic effects exists no consense in the scientific world, because there is
 still a lack of a theoretical base to explain epigenetic phenomena.
I try to understand them on the base of Selforganisation Theory in that way that non-linear
 events (e.g. small cause, big effect) provoke the emergence of coherent behavior of specific
 agents present, effecting the generation of a new informational state of the cell. In mathematical
 terms this means that e.g.the cells of a multicellular organism tend towards different attractors,
 which represents a defined physiological state cells and differentiate them into cells with diverse
 behavior, constituting different tissues, although all the cells contain the identical genetic information.

Best wishes
 Guenther
guenther ellersdorfer
institute of microbiology and genetics
department: microbiology and biotechnology
A-1030 Vienna
Dr. Bohrgasse 9
FON +43 1 79515 4122
FAX +43 1 7986 224
Received on Tue Apr 14 05:01:40 1998