Having completed the sequencing of the human genome and model animals and plants, molecular biology is shifting to a new era of decoding the modulation mechanism of micromolecular activities' entire process, led by gene expression and signal regulation. At present, postgenome-era molecular biology is brewing theoretically and experimentally a new breakthrough. Its core is to break away from the original "gene-centered" or "genetic determinism" framework, and place the development of the postgenome on two new and important experimental understandings.
First, only the bionetworks form the cell-objective modulation basis of all life activities. The importance of bionetworks has been greatly enhanced, and bionetworks have become the new objects for theoretical and experimental research of molecular modulation mechanisms.
Second, the process of gene expressed to phenotype is regulated and influenced by both internal and external environmental factors. The concept "DNA sequence is the deterministic blueprint for development" has been changed, and how to integrate internal and external signals to regulate gene expression becomes the new core issue.
Molecular biology, biochemistry, structural biology, and other disciplines have achieved such great success that it is possible to carry out specialized analysis and experimentation on the detailed processes of an organism's structures, functions, and metabolic pathways. Facing the ever-increasing mountain of experimental data and information, many branches of contemporary life science¡ªwhich successively includes reductionist research on higher animals behavior, brain neural information coding, metabolic networks, and genetic modulation¡ªinvariably encounter a common question: what theory and methods can effectively integrate the vast amounts of data and information?
At present, among the new theories and methods of postgenome research, there are two brewing developmental directions that urgently require attention.
One is the new research framework of systematic biology. It is hoped that through systematic simulation and interference experimentation, we can globally and synthetically realize the computing and modeling of huge quantities of data to push the gene annotation up to the network and system level.
The other is the new theoretical innovation of "deep structure."
Based on the deep structure theory, the standard of effective integration of bioinformation is whether it can identify the relevant mutual combinations and matching relationships when various bioinformation is reflecting an organism's physio-ecologically variable goals.
The DSS books suggested that the greatest difficulty facing the development of contemporary life sciences is how to successfully extend the cell and molecular level experimental knowledge to the analysis of phenotypic variable processes, such as an organism's behavior, movement, and physiology. This problem has been encountered successively at all levels and in many fields of contemporary life science. That is essentially the so-called life-modulation mechanism.
DSS books summed up the experiences of previous studies of the life-modulation mechanism, and suggested that any level of functional research, when it had finished the substantive analysis of fragments, would surely go to the study of the modulation mechanism. But the analysis of modulation should not purely trace down the functional pathway process, because the secret of modulation was not hidden in the procedure, but was contained in the meaning of being designed into the procedure. That is to say, the essence of modulation research is not to investigate functional problems, but to explore the being's design of functions¡ªnamely the deep-structure problems.
In the traditional doctrine, genotype is the basic unit of biological adaptation, and the dispersing efficiency of the genotypes in relation to niches is the interpretation standard of biological adaptation. Phenotypic plasticity studies have provided different empirical evidence that a particular genotype in different environments can express different phenotypes. Phenotype uses its plasticity to respond to the changes in the environment. Evidence has shown that the genetic restriction to phenotype is not as simple and direct as originally imagined. Organisms maintain their optimality through the conversion of different phenotypes and different responses to environmental conditions. In other words, in the traditional doctrine, one genotype can only form a set of phenotype system; while the new deep-structure theory believes that a genotype can form multiple sets of phenotype system. This change in biological theory breaks away from the original "gene¨Cphenotype" theory, going toward the new "gene¨Cvitastate¨Cphenotype" theoretical direction.
The phenotypic plasticity studies and discoveries that individuals with the same genotype can, in their lifetime, actively make multiform responses (in the broad sense of physiological phenotype) to environmental signals provide a new perspective for understanding the postgenome.
The phenotypic plasticity studies also have important impacts on the traditional genetic determinism for an organism's development. Phenotypic plasticity study found that the process of gene expressed to phenotype is regulated and influenced by both internal and external environmental factors. This reveals the role played by concrete environmental changes in the complex physiological process of phenotypic regulation. Because of the plasticity research, developmental biology has moved beyond the traditional view that "DNA sequence is the deterministic blueprint for development," and understands the organism as a developmental system that continuously integrates both internal and external signals to regulate gene expression. At present, the study of developmental plasticity is leading developmental biology toward the specific processes of the bionetwork-centered molecular transmission mechanism and the regulation system.
The new deep-structure theory concludes that phenotypic plasticity and like research is essentially the study of "phenotypic optimality." That is the microphysiology-based eco-optimality comparative analysis of intraspecific phenotypic physiology.
The "phenotypic optimality" research might provide physiology-level possibilities for explaining adaptation. This is manifested in two new understandings: 1) Intraspecific ecological optimality of phenotypic physiology can be explained as: with the genotype's phenotypic physio-morphs, the organism respectively forms the efficiency advantage corresponding to the niche variables. 2) The physio-morph activities of functional operation can be interpreted as: the organism's component behavior is subjected to different modulation restrictions in different phenotypic physio-morphs. To sum up, the physiology of adaptation can be expressed as: the organism uses different restrictions to component behavior, formed holistically and with self-modulations, to create different phenotypic advantages that aim at different niche conditions.
The deep-structure theory suggested that experimental studies of phenotypic plasticity, by comparing the conversion of different phenotypes (especially at the microphysiological level) in response to specific environmental conditions, could discover the optimality of different strategies, and that these methods could be furthered to deep-structure experimental analytic theory and used as an analytic tool for solving the bionetwork and molecular modulation mechanism. Among them, the strategy comparison of phenotypic changes being transferred to deep-structure analysis can help in detecting the dividing line of molecular bionetwork, while the comparative analysis between ecology and physiology being transferred to deep-structure analysis can help solve the problem of how external factors and internal genes microphysiologically form the life-modulation mechanism. Deep-structure analysis finds a new path for the development of the postgenome experimental biology.
New theory suggested that life's functional process can be discovered by experimental methods, but life-modulation mechanisms cannot be revealed by purely functional experimental methods; rather, they need to associate with the comparative study of vitastates to reveal the life-modulation mechanism. By comparing the physio-morphs of physiological vitastates, we can discover and create the life-modulation mechanism's meaning system and realize reductionist study on biological meaning system. This principle and method was named as Molecular Network Deep Structure Study in the DSS¢ò..
The molecular deep-structure theory is that, during the molecular modulation process, the response relation among each fragmental molecular process implicates the upper-level holistic physio-ecological goals. Natural selection endows certain molecular behavior the coordinated start-up ability consistent with other molecular behaviors; and this start-up (namely "vitastate"), by its role in ecological decompression of the global organism, optimizes the organism's costs and benefits. Thus, if we understood the advantages and disadvantages of starting up certain vitastates when facing some ecological pressures, we might naturally realize which start-up vitastate the organism would modulate. Therefore, the essence of objective modulation is a deep-structure problem.
Therefore, the identification of the meaning of certain molecular functionality can only be realized through vitastates' comparative study. No matter what the meaning analysis of the functionality of molecular modulation is, it can go nowhere without the vitastates comparative study. The traditional "molecular path tracking" approach cannot identify that among the gone-through pathways: which one is early and which one is late, which is heavy and which is slight, which is pressing and which is otherwise, which is variant and which is similar. It also cannot distinguish the original creating relationship (namely the meaning relationship) between one molecular function's detailed process and that of another molecular function. Therefore, when tracking along the transferring molecular pathways, a series of problems may occur, such as various functions in their pathway details presenting cross, repeat, loop, bifurcation, complex, overlapping, and so on. Ultimately, the molecular path tracking might be trapped into trouble because of "information explosion."
So deep structure theory insists that experimental biology is facing a required revamping of its theories and methods from the cell's molecule, gene, regulatory factor, and bionetwork levels to explain an organism's high-level problems such as physiology, behavior, development, pathological mechanism, and so on. To detect the secret of the molecular life-modulation mechanism, the introduction of molecular deep-structure study has an important and directional significance.
One of the deep structural applied projects is the deep structure research of signal modulation mechanism of life in vivo at the molecular level£®