Functional genetics

The idea that there are quantitative bonds between DNA and RNA and that the study of these bonds leads to heredity management has existed since the formation of modern ideas about the biological role of nucleic acids . It is reflected in the generally accepted scheme for the transfer of genetic information from DNA to RNA and protein and in the title of the global scientific problem - “study of the structure and function of the cell genome ”. Functional genetics makes it possible to experimentally study directly the “function” of the genome ( molecular biology studies the “structure”).

In the middle of the last century, many scientists tried to identify the relationship between DNA and RNA . For this purpose, the biochemical method of Schmidt and Tanghauser (1945) was widely used, which allows one to determine the ratio of RNA / DNA or DNA / RNA in cells isolated from animal tissues . The end result characterized the cell population . To overcome the limitations of the method, researchers turned to quantitative cytochemistry. The pioneers in its formation were cytologists , who traditionally use microscopes and various methods of staining cells. From the very beginning, it was clear that as the creation and implementation of quantitative cytochemistry methods, the science of the cell will acquire a new quality. Quantitative cytochemistry, by definition, is an interdisciplinary field in science. In the process of its formation, an entire industry arose to create special measuring instruments: measuring microscopes, flow fluorimeters and other means of automation of cytological studies. At the same time, new ones were created and known cytochemical methods were modified, and the sources of specific errors of the measurement method as a whole were also investigated. Similar works carried out at the Institute of Chemical Physics of the Academy of Sciences of the USSR in the period from 1966 to 1993 made it possible to establish several quantitative laws related to the main topic (1-6).

Cell populations homogeneous by morphological characteristics were studied. The content of DNA and RNA was determined in each cell. The results of their measurements in the form of dots were plotted on a graph where the DNA content is plotted along the abscissa axis, and the total RNA content is expressed along the ordinate axis, expressed in uniform weight units - ploidy units “c” (constant for the type of animal). The result is a certain two-dimensional distribution of points on a plane in the coordinates of DNA-RNA, similar to a starry sky . It has been observed that:

1. The boundaries of the two-dimensional distributions of cell populations homogeneous in morphological characteristics in the accepted coordinates correspond to the shape of simple geometric figures such as an ellipse and trapezoid . The sizes of the figures and their position on the graph are constant for cells of a certain type and do not depend on the type of animal.
2. The shape of the distribution of the measurement results of mixed cell populations on the graph corresponds to the sum of several simple geometric shapes .
3. In the study of cells in the proliferative dormant phase, the shape of the distribution of the cell population in the coordinates of DNA-RNA corresponds to a vertically located ellipse, the large diameter of which falls on 2c of DNA (for “normal”) or a multiple indicator if polyploid cells are examined. A small diameter indicates a method error.
4. If the population consists of proliferating (in the synthesis phase) cells, then its shape corresponds to the trapezoid . Its parallel sides are in 2s and 4s of DNA, and the inclined sides are located at different angles to the abscissa axis. It was noted that the upper boundary of the distribution almost coincides with the bisector of the coordinate angle. It accounts for the results of measurements of the least differentiated (according to morphological characteristics) cells. On the lower border are the results of measurements of the most differentiated cells (thymocytes and bone marrow cells were examined). It has also been observed that the average amount of RNA in cells increases monotonically with increasing DNA content.
5. The data presented in paragraphs 3 and 4 speak of two methods of “functioning” of the cell genome - one is carried out during the synthesis phase, the other - during the proliferative dormancy phase, as well as the existence of a direct relationship between the content of DNA (x) and RNA ( s) in normal proliferating cells. This dependence is described by the formula y = ax, where a is the coefficient. It has been suggested that this coefficient is a new variety of biological constants and, at the same time, a multifunctional indicator: the relative rate of RNA biosynthesis (v is the kinetic parameter), as well as an indicator of the proportion of the genome that "functions" in cells of a certain type and its unique quantitative passport.
6. The data presented in paragraph 4 and the assumptions of paragraph 5 made it possible to formulate a hypothesis according to which in a population of proliferating and differentiating cells - in thymocytes (the traditional model for studying the process of cell differentiation), there are several groups of cells with different RNA / DNA ratios. The hypothesis was confirmed. The number of such groups was established n = 6, the values ​​a1 = 1 were estimated; a2 = 0.82; a3 = 0.64; a4 = 0.44; a5 = 0.28 and a6 = 0.19 and the probability of transition of daughter cells formed during mitosis to the next stage of the process of cell differentiation (p ~ 0.75). So for the first time in world practice, the kinetic parameters of the process of cell differentiation were evaluated.

The methodology of functional genetics is common with biophysics . The only difference is that biophysics was created by physicists who came to biology with their knowledge and scientific values.

As a result, modern biophysics is interpreted as "physics of the living." Functional genetics does not use the knowledge of physicists, but the logic of their thinking. The goals and objectives of scientific research, as well as the selection of the necessary cellular models, are entirely dependent on biologists. Cytologists evaluate the morphology of cells, give them a certain biological meaning, and on this basis determine the tactics of subsequent scientific research. This is no longer “living physics”, but the biology of the future. The methodology of Functional Genetics is based on kinetics , as a science of the rates of various, including biological, processes (teachings of N.N. Semenov and N.M. Emanuel ). Its rules (the rules of mathematics ) form the features of a professional language, in which the first place is the requirement for the accuracy (uniqueness) of the terms and concepts used. This applies, in particular, to the word " cell ". The reigning methodology in modern biology is “ phenomenology ”, which is natural for the early stage of the development of science. Accordingly to this methodology, the word “cell” means a stationary, abstract, averaged “image” of a cell that matches its pattern or photograph from a biology textbook. The stationary “image” is opposed by the “kinetic image” (or “kinetic model of the cell”), which has the form of one or more lines on the DNA-RNA graph, which reflects the life path of a cell of a certain type. Such an “image” (or “model”) makes it possible to study “kinetics of intracellular biological processes” on fixed (dead) cells, and the term “biological processes” refers to any manifestations of its vital activity characterized by regular quantitative and qualitative features of the functioning of the genome. As before, the cell population remains the source of knowledge about the “cell”. Under previous conditions, scientists could not identify quantitative relationships between DNA and RNA, since they studied the total properties of cell populations that are always complex in composition. In ordinary populations, cells outside the synthesis phase (from 80 to 100%) predominate. They do not have an explicit connection between DNA and RNA - the RNA content varies depending on the activity of the cells, while the DNA content remains constant. Of particular scientific value is the study of the coefficient a (RNA / DNA) and the kinetic parameters of the process of cell differentiation. Their establishment and systematization open up fundamentally new opportunities in studying the mechanisms of genome functioning and solving a number of applied problems, including the management of heredity.

• Pereverzev B.L. “The amount of RNA in the life cycle of normal and tumor cells” - DAN USSR, 1978, Volume 241, No. 4, pp. 946-948.
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• Pereverzev B.L. “Quantitative cytochemistry of nucleic acids of normal and malignant cells” - Diss. Doctor of Science. Kiev, 1988.
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• Pereverzev B.L. “Two genetics. Functional genetics as the basis of future biology ”- Bulletin of the Siberian Branch of the Academy of Military Sciences, 2015, No. 31, p.188-194.