Molecular Genetics definition of Molecular Genetics in the …

a branch of genetics and molecular biology concerned with learning the material bases of heredity and variation in living things by investigating on the subcellular molecular level the processes of the transmission, materialization, and alteration of genetic information and the methods of storing that information.

Molecular genetics became an independent discipline in the 1940s as a result of the application of new physical and chemical methods to biology (X-ray diffraction analysis, chromatography, electrophoresis, high-speed centrifugation, electron microscopy, the use of radioactive isotopes). These methods made possible a deeper and more accurate study of the structures and functions of individual cell components and of the entire cell as a unified system. In addition, new ideas from chemistry, physics, mathematics, and cybernetics were introduced into biology. Molecular genetics to a large extent owes its rapid development to the transfer of the focus of genetic research from higher organisms (eucaryotes)the principal subjects of classical geneticsto lower organisms (procaryotes)bacteria, viruses, and many other microorganisms. The advantages of using simpler forms of life to solve genetic problems consist in the rapid succession of generations in these forms and the possibility of studying numerous individuals simultaneously; this leads to an increase in the resolving power and accuracy of genetic analysis. In addition, the relative simplicity of organization of bacteria, especially of viruses, facilitates elucidation of the molecular nature of genetic phenomena. The opinion sometimes expressed that molecular genetics and the genetics of microorganisms are one and the same is erroneous. Molecular genetics studies the molecular bases of genetic processes in both lower and higher organisms and does not include the specific genetics of procaryotes, which occupies a prominent place in the genetics of microorganisms.

During its short history, molecular genetics has made great strides, deepening and broadening our knowledge of the nature of heredity and variation; it has become the leading and most rapidly developing branch of genetics.

One of the main achievements of molecular genetics is the elucidation of the chemical nature of the gene. Classical genetics established that all hereditary potentials of organisms (their genetic information) are determined by discrete units of heredity called genes, which are located mainly in the chromosomes of the cell nucleus and in some organelles of the cytoplasm (plastids, mitochondria). However, the methods of classical genetics were unable to elucidate the chemical nature of the genes, which was noted as far back as 1928 by the outstanding Soviet biologist N. K. Koltsov, who substantiated the necessity of studying the mechanism of heredity on the molecular level. The first success in this area was achieved with the study of genetic transformation in bacteria. In 1944 the American scientist O. T. Avery and his associates discovered that hereditary characteristics of one type of pneumococcus could be transmitted to another, genetically different type by introducing into its cells the deoxyribonucleic acid (DNA) obtained from the first type. Subsequently, a similar genetic transformation by means of DNA was accomplished in other bacteria and recently in some multicellular organisms (flowering plants and insects).

Thus, it was shown that the genes consist of DNA. This conclusion was confirmed by experiments with DNA-containing viruses: it is sufficient to inject molecules of viral DNA into the cell of a susceptible host to cause the virus to reproduce; all the other components of the virus (proteins, lipides) lack infectious properties and are genetically inert. Similar experiments with viruses containing ribonucleic acid (RNA) instead of DNA have shown that the genes in these viruses consist of RNA. Clarification of the genetic roles of DNA and RNA served as a powerful stimulus to the study of nucleic acids by biochemical, physico-chemical, and X-ray diffraction methods.

In 1953 the American scientist J. Watson and the British scientist F. Crick proposed a model of the structure of DNA, hypothesizing that its gigantic molecules consist of a double helix made up of a pair of strands formed by nucleotides, arranged aperiodically but in a definite sequence. Each nucleotide of one strand is paired with an oppositely situated nucleotide of the other strand according to the rule of complementarity. Numerous experimental data have confirmed the Watson-Crick model. Somewhat later it was established that the molecules of various RNAs have an analogous structure but that they consist for the most part of a single polynucleotide strand. Later research, in which chemical and physicochemical methods were combined with precise genetic methods (for example, the use of various mutants and the phenomena of transduction and transformation) showed that different genes differ in the number of nucleotide pairs (from several dozens to 1,500 or more), as well as in the sequence of nucleotides, which is strictly determined for each gene and in which the genetic information is encoded. Genes consisting of RNAin viruses of the RNA-typehave a fundamentally similar structure.

Classical genetics regarded the gene as a discrete and indivisible unit of heredity. The works of A. S. Serebrovskii and his students in the 1930s, which first suggested the possibility of the divisibility of the gene, were of great significance in the reexamination of that concept. However, the resolving power of the methods of classical genetics was inadequate for the study of the fine structure of the gene. It was only with the development of molecular genetics in the 1950s and 1960s that it became possible to solve this problem. Through many studies, first conducted on bacteria and viruses and then on multicellular organisms, it became clear that the gene has a complex structure: it consists of tens or hundreds of sectionssiteswhich are capable of mutating and recombining independently. The limit of divisibility of a gene, and consequently the minimal size of a site, is one pair of nucleotides (in viruses containing one RNA strand, one nucleotide). Determination of the fine structure of genes has made possible a deeper insight into the mechanism of genetic recombination and the principles of the origin of gene mutations; it has also promoted elucidation of the mechanism of gene function.

Data on the chemical nature and fine structure of genes have made it possible to develop methods of isolating them. This was first done in 1969 by the American scientist J. Beckwith and his associates for one of the genes of Escherichia coli. Subsequently, the same was successfully accomplished in some higher organisms (amphibians). An even more significant achievement of molecular genetics was the first chemical synthesis of a gene (the one that encodes the alanine transfer RNA of yeasts), accomplished by H. Khorana in 1968. Studies of this kind are being conducted throughout the world. The latest biochemical methods, based on the phenomenon of reverse transcription( see below), have been successfully used for the extracellular synthesis of larger genes. Using these methods, S. Spiegelman, D. Baltimore, P. Leder, and their associates (USA) have made great progress in artificially synthesizing the genes that determine protein structure in hemoglobin molecules of rabbits and humans. Similar studies have recently been conducted elsewhere, including the USSR.

Thus, molecular genetics has already explained, in theory, how genetic information received by offspring from parents
is recorded and stored, although much work is still required to decipher the detailed content of that information for each individual gene.

Determination of the DNA structure has paved the way for experimental investigation of the biosynthesis of DNA molecules that is, their replication. The process of DNA replication is the basis for the transfer of genetic information from cell to cell and from generation to generationthat is, it determines the relative constancy of genes. Study of DNA replication has led to the important conclusion of the template nature of DNA biosynthesis: in order for biosynthesis to take place, the presence of a completed DNA molecule is necessary, upon which, as on a template, the new DNA molecules are synthesized. In this process, the double helix of DNA unwinds, and on each of its strands a new, complementary strand is synthesized; as a result, the daughter DNA molecules consist of one old and one new strand (semiconservative replication). The protein that induces unwinding of the double helix of DNA and the enzymes that carry out the biosynthesis of nucleotides and their linkage have been identified. Undoubtedly, there are mechanisms in the cell that regulate DNA synthesis. The means of such regulation are still largely unclear, but it is evident that regulation is largely determined by genetic factors.

Excerpt from:
Molecular Genetics definition of Molecular Genetics in the ...