| Artificial life (ALife) is one of new development directions after artificial intelligence (AI) appearing in the computer science. Construct and research of electronic cell (E-Cell) model based on ALife theory is one of the important research directions.People are apt to think that the most basal change of science will be the material is replaced by the information since the 21st century, is also transform process from the attention of system material composition to the attention of system information or function characteristic. Complex science is a burgeoning science discussed emergent characteristic between each interacted part, natural life system is a high complex self-adaptive system. Complex and advanced dynamic behavior and structure are emerged by simple and preliminary behavior and structure under the simple and partial rules. The life is the emergent characteristic, is a result that DNA molecules, protein molecules and the other innumerable kinds of molecules have been obeying chemistry theorem. Cellular automata model proposed by John Von Neumann has developed the research that certain life characteristics are realized with man-made media; Christopher G. Langton has further developed this idea and proposed the concept of ALife.ALife is a science which researches artificial systems having behavior characteristics of natural life system. It attempts to simulate and synthesize some basic life phenomena on the computer or other artificial media, such as self-duplication, evolution and so on, thus enables the people to deeply understand the known life phenomena. ALife and AI are similar, the difference is only that ALife simulates basic evolving biological mechanisms and life with the computer, but AI simulates the thinking process. Basic ideas of ALife research are: 1) Essence of life lies in the form, don't lie in the concrete material. Life is abstract, namely life characteristics does not exist in the single material, but exist in the material organization. ALife pays attention to grasp the generality of life, and shifts life to different carriers. 2) Emergent is prominent characteristic of life. In the complex status many relative simple units interact with each other; the life emerges many noticeable new overall characteristics. 3) Life isn't only similar to the computer; it is a kind of algorithm radically. Evolution process of life can be regarded as a process computation complexity growing unceasingly. 4) Research methods of ALife are the synthesized methods. ALife makes use of the method that combines simple part to produce the life behavior, namely researches the life with synthesized method, and attempts to synthesize the process and behaviors of the life on the computer or other media.Construct and research of E-Cell model is one of important research directions of ALife, is a brand-new method that using modern information technology for the research of the cells. E-Cell is also called virtual cell, it constructs a virtual cell system on the computer by the knowledge of the cells that people grasp and mathematical analysis of accumulated massive biological data, simulates and reappears internal and external structure, material composition and life activities of true cell, realizes digital simulation of biological reaction process, is used to explore and discover new rules of life activities of the cell.Development of E-Cell can be divided into three stages on the whole: 1) constitution stage, mainly includes the simulation of material composition and basic functions of the cell, establishment of knowledge database about dynamics behavioral characteristics of internal and external environment and material composition of the cell, establishment of surface for man-machine interaction or visualization and network design platform; 2) realization stage, mainly is that function behaviors of the cell are simulated, experimented, optimized and perfected; 3) application stage, E-Cell model having great ability of simulating true cells will be an indispensable and important tool in the medicine, biology, biochemistry project and so on practical application domains. At present international research is still at the first stage, namely constitution stage.E-Cell simulates the whole process of life activities of the cell on the computer, mainly simulates the growth, reproduction and death of the cell. It mainly includes the following several research directions: 1) modeling for composition, structure and function of the cell; 2) simulating the process of gene expression; 3) researching on intercellular communications and mechanisms of signal transmitting; 4) simulating and analyzing of cellular metabolism process; 5) forecasting of protein synthesis and structure; 6) researching on evolution mechanism. This thesis proposed E-Cell model, named Analog-Cell, has mainly realized the simulation of gene expression process, and has simulated and researched the main way of cell evolution - gene mutation.Many researchers have launched the research about E-Cell model, but they do only pay attention to certain aspect of the entire cell system, haven't achieved the whole level of simulation, therefore the research of E-Cell stays on simple computer model. At present there are three kinds of ripe E-Cell models: Japan constructs E-CELL model simulating energy metabolism and material transmitting through cell membrane of prokaryote; US constructs Virtual Cell model simulating transmitting of calcium ion stream of eukaryotic cell; US constructs CyberCell model simulating stimulation response of the cell for environment, material transmitting and genome change. But these E-Cell models all have a general insufficiency: although simulation result contains complete statistic of energy data, they are actually simple in graphical display, aren't favorable in observing life activities of the cell.This thesis proposed a new E-Cell model, named Analog-Cell, and has realized simulation of gene expression of eukaryote. Its advantage lies in containing the more ample image information of cell action, on the other hand lies in simulating one of the ways of cell evolution - gene mutation. In order to satisfy the researchers to observe life activities of the cell, summarize and discover biological phenomenon and rules of the cell, four aspects work followed are done:1) Constructing the first domestic E-Cell model - Analog-Cell.E-Cell has simulated life activities of the cell on the computer. Academic forecast get from the model should reflect accurately as far as possible the authenticity of biological system. Modeling idea of concurrent constraint has general function character of structure and function with living system. Analog-Cell is E-Cell model which regards eukaryote as research object, vividly simulates the process of gene expression that DNA sequence is transcribed into mRNA and mRNA is translated into polypeptide chain. This polypeptide chain is pre-protein of various enzymes or regulative factors. It will affect activities of the entire cell finally. We constructs stochastic model based on concurrent constraint in Analog-Cell, regards the number of existing various molecular in E-Cell system as system state list, its state transformation has really reflected life activities of the cell, such as reactions catalyzed by enzymes, the regulation of gene expression and so on. It simplifies the complex of cell biological mechanism.In order to make Analog-Cell simulate really the process of gene expression on molecular level, we chose some materials related with gene expression, such as DNA sequence, five kinds of nucleotides, mRNA, ribosome, tRNA, twenty kinds of amino acids, polypeptide chain and various regulative factors and so on. Simulated method of Analog-Cell is dividing materials that gene expression related into three kinds: substances, gene sequence and reaction rules. All molecules related with gene expression are defined substance in the cell. Gene sequence transmits genetic information to the protein through mRNA, thus decide structure and function of proteins which affect cell activities. Reaction rules are the core of the model that conform substances and gene sequence. They control reaction process through defining reaction process of gene expression and the state of substances.According to biological theory of gene expression, gene expression simulated by Analog-Cell is mainly composed of three processes: transcription, translation and degradation. Transcription is synthesis process of mRNA; Translation is synthesis process of polypeptide chain; Degradation is the process that mRNA is decomposed by exonuclease. The orderly accomplishing of transcription, translation and degradation is a complete process of gene expression. In order to reappear really life activity of gene expression in the cell, we propose the algorithms that simulate transcription and translation. Simulative results indicate that gene expression simulated by Analog-Cell conforms to biological theory, so its design is completely reasonable.2) Researching and simulating the main regulative mechanism of gene expression in Analog-Cell.The regulation of gene expression decides quantity, ingredient and function of proteome that genetic information of genome express, proteome affects life activities of the cell, thus decided biochemistry characteristics of the cell. Existing E-Cell models simulate few for the regulation of gene expression. Each step from gene to protein is controlled by regulation of certain degree, including transcription level (transcription initiation, transcription process, after transcription) and translation level. It is generally thought that transcription initiation is an important link in regulative mechanisms, is first-level regulation of gene expression, and decides what genes specific cell does express in the special time. Regulation after that is second-level regulation, is responsible to regulate the quantity of synthesized protein, and changes properties of the protein.In order to simulate gene expression really, E-Cell needs to realize basic regulative mechanisms. In the regulation of gene expression the function of various regulative factors and enzymes is main body of regulative mechanisms. We define some main regulative factors and enzymes in Analog-Cell, such as RNA polymeraseâ…¡which is responsible to transcribe genes of encoding proteins; initiation factors, named eIF-2 and eIF-3, which catalyzed pre-initiation complex to combine with mRNA in translation; elongation factor, named eEF-2, which catalyze movement of the ribosome to identify next codon; release factor, named eRF-1, which is responsible to identify terminational-codon; aminoacyl-tRNA synthetase which catalyzed the synthesis of tRNA and the corresponding amino acid; peptidyl transferase which catalyzed the synthesis of peptide bond between two amino acids and so on.We define reaction rules which conforms to the theory of reactions catalyzed by enzymes and proposed several regulative algorithms that realize regulative mechanisms, such as mRNA is a polymer consisting of four kinds of ribonucleotide under the catalysis of RNA polymeraseâ…¡; Polypeptide chain is a polymer consisting of twenty kinds of amino acids under the catalysis of various regulative factors; algorithm undoing helix of DNA double chain before transcription; algorithms realizing initiation and termination of translation and so on. Simulative results indicate that definition and design of these reaction rules and regulative algorithms are completely reasonable, provide the effective method to simulate really the process of gene expression.3) Researching and realizing the examination and identification of promoter in Analog-Cell.DNA is expressed which regards a gene as a unit. Eukaryote promoter is sequence which is influential to transcription initiation; it identifies the initiation position of each gene on DNA. It includes core promoter that controls whether gene is transcribed and upstream promoter element that enhances foundational speed of transcription initiation.We propose promoter identification algorithm based on the method of position weight matrix in Analog-Cell, so the model realizes examination and identification of TATA box and initiator sequence (Inr) of core promoter. According to this algorithm, if TATA box isn't examined in DNA sequence, this sequence cannot be expressed; if TATA box is examined, we need to determine transcription initiation position namely Inr and translation initiation position namely initiation codon AUG, thus DNA sequence is intercepted, simulative process of gene expression begins.4) Researching and simulating gene mutation on the molecular level. Genome evolution is accumulative result through sequence change of small scale aroused by mutation and rearrangement of large-scale aroused by recombination. The most mutations are point mutation that single nucleotide is replaced, other forms include insertion or deletion of one or several nucleotides. Mutation occurred on an essential gene of germ cell is very important for biological evolution. But probability of mutation occurring is very infrequent in the cell.Analog-Cell implements simulation on the molecular level, namely DNA is composed of many nucleotides, but is not composed of the genes. It provides condition for simulating gene mutation. Analog-Cell has simulated many kinds of gene mutations, such as point mutation, insertion and deletion. We simulate gene mutation and propose simulative algorithm toward to typical point mutation. It uses the method that a random number divided by a biggish integer to control probability of occurring mutation. It conforms to objective fact that gene mutation occurs infrequently in the biology.Through gene mutation simulated by Analog-Cell, which doesn't existed other E-Cell models, we can observe that the gene occurring mutation expresses to different polypeptide chain with the original, thus this polypeptide chain becomes different protein which affects life activities of the cell. It provides the possibility for researching on basic biological mechanisms of cell evolution.In conclusion, the achievements of this thesis have a certain theory significance and application importance for constructing and developing the E-Cell models. It provides the effective methods and the means for simulating life activities of the cell on the whole, summarizing and discovering the new biological phenomenons and the rules of the cell of the life activities.
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