gene(redirected from dhfr gene)
Also found in: Dictionary, Thesaurus, Medical.
gene,the structural unit of inheritance in living organisms. A gene is, in essence, a segment of DNA that has a particular purpose, i.e., that codes for (contains the chemical information necessary for the creation of) a specific enzyme or other protein. The strands of DNA on which the genes occur are organized into chromosomeschromosome
, structural carrier of hereditary characteristics, found in the nucleus of every cell and so named for its readiness to absorb dyes. The term chromosome
..... Click the link for more information. . The nucleus of each eukaryotic (nucleated) cell has a complete set of chromosomes and therefore a complete set of genes. Each gene provides a blueprint for the synthesis (via RNA) of enzymes and other proteins and specifies when these substances are to be made (see nucleic acidnucleic acid,
any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis.
..... Click the link for more information. ). Genes govern both the structure and metabolic functions of the cells, and thus of the entire organism and, when located in reproductive cells, they pass their information to the next generation.
Chemically, each gene consists of a specific sequence of DNA building blocks called nucleotides. Each nucleotide is composed of three subunits: a nitrogen-containing compound, a sugar, and phosphoric acid. Genes may vary in their precise makeup from person to person, including, for example, one nucleotide in a certain location in some people but another nucleotide in that location in others. Geometrically, the gene is a double helix formed by the nucleotides. Gene loci are often interspersed with segments of DNA that do not code for proteins; these segments are termed "junk DNA." When junk DNA occurs within a gene, the coding portions are called exons and the noncoding (junk) portions are called introns. Junk DNA makes up 97% of the DNA in the human genome, and, despite its name, is necessary for the proper functioning of the genes.
Each chromosome of each species has a definite number and arrangement of genes. Alteration of the number or arrangement of the genes can result in mutationmutation,
in biology, a sudden, random change in a gene, or unit of hereditary material, that can alter an inheritable characteristic. Most mutations are not beneficial, since any change in the delicate balance of an organism having a high level of adaptation to its environment
..... Click the link for more information. . When the mutation occurs in the germ cells (egg or sperm), the change can be transmitted to the next generation. Mutations that affect somatic cells can result in certain cancerscancer,
in medicine, common term for neoplasms, or tumors, that are malignant. Like benign tumors, malignant tumors do not respond to body mechanisms that limit cell growth.
..... Click the link for more information. .
The scientific study of inheritance is geneticsgenetics,
scientific study of the mechanism of heredity. While Gregor Mendel first presented his findings on the statistical laws governing the transmission of certain traits from generation to generation in 1856, it was not until the discovery and detailed study of the
..... Click the link for more information. . The genetic makeup of an organism with reference to its set of genetic traits is called its genotype. The interaction of the environment and the genotype produces the observable attributes of the organism, or its phenotype. The sum total of the genes contained in an organism's full set of chromosomes is termed the genome. Scientists are working toward identifying the location and function of each gene in the human genome (see Human Genome ProjectHuman Genome Project,
international scientific effort to map all of the genes on the 23 pairs of human chromosomes and, to sequence the 3.1 billion DNA base pairs that make up the chromosomes (see nucleic acid).
..... Click the link for more information. ). The decoding of the first free-living organism (a bacterium, Hemophilus influenzae) was completed in 1995 by J. Craig Venter and Hamilton Smith.
See also gene therapygene therapy,
the use of genes and the techniques of genetic engineering in the treatment of a genetic disorder or chronic disease. There are many techniques of gene therapy, all of them still in experimental stages.
..... Click the link for more information. ; genetic engineeringgenetic engineering,
the use of various methods to manipulate the DNA (genetic material) of cells to change hereditary traits or produce biological products. The techniques include the use of hybridomas (hybrids of rapidly multiplying cancer cells and of cells that make a
..... Click the link for more information. .
The basic unit in inheritance. There is no general agreement as to the exact usage of the term, since several criteria that have been used for its definition have been shown not to be equivalent.
The facts of mendelian inheritance indicate the presence of discrete hereditary units that replicate at each cell division, producing remarkably exact copies of themselves, and that in some highly specific way determine the characteristics of the individuals that bear them. The evidence also shows that each of these units may at times mutate to give a new equally stable unit (called an allele), which has more or less similar but not identical effects on the characters of its bearers. These hereditary units are the genes, and the criteria for the recognition that certain genes are alleles have been that they (1) arise from one another by a single mutation, (2) have similar effects on the characters of the organism, and (3) occupy the same locus in the chromosome. It has long been known that there were a few cases where these criteria did not give consistent results, but these were explained by special hypotheses in the individual cases. However, such cases have been found to be so numerous that they appear to be the rule rather than the exception. See Allele, Gene action, Mendelism, Mutation, Recombination (genetics)
The term gene, or cistron, may be used to indicate a unit of function. The term is used to designate an area in a chromosome made up of subunits present in an unbroken unit to give their characteristic effect. See Chromosome
Every gene consists of a linear sequence of bases in a nucleic acid molecule. Genes are specified by the sequence of bases in DNA in prokaryotic, archaeal, and eukaryotic cells, and in DNA or ribonucleic acid (RNA) in prokaryotic or eukaryotic viruses. The ultimate expressions of gene function are the formation of structural and regulatory RNA molecules and proteins. These macromolecules carry out the biochemical reactions and provide the structural elements that make up cells. See Deoxyribonucleic acid (DNA), Nucleic acid, Ribonucleic acid (RNA), Virus
One goal of molecular biology is to understand the function, expression, and regulation of a gene in terms of its DNA or RNA sequence. The genetic information in genes that encode proteins is first transcribed from one strand of DNA into a complementary messenger RNA (mRNA) molecule by the action of the RNA polymerase enzyme. Many kinds of eukaryotic and a limited number of prokaryotic mRNA molecules are further processed by splicing, which removes intervening sequences called introns. In some eukaryotic mRNA molecules, certain bases are also changed posttranscriptionally by a process called RNA editing. The genetic code in the resulting mRNA molecules is translated into proteins with specific amino acid sequences by the action of the translation apparatus, consisting of transfer RNA (tRNA) molecules, ribosomes, and many other proteins. The genetic code in an mRNA molecule is the correspondence of three contiguous (triplet) bases, called a codon, to the common amino acids and translation stop signals; the bases are adenine (A), uracil (U), guanine (G), and cytosine (C). There are 61 codons that specify the 20 common amino acids, and 3 codons that lead to translation stopping. See Genetic code, Intron
In many cases, the genes that mediate a specific cellular or viral function can be isolated. The recombinant DNA methods used to isolate a gene vary widely depending on the experimental system, and genes from RNA genomes must be converted into a corresponding DNA molecule by biochemical manipulation using the enzyme reverse transcriptase. The isolation of the gene is referred to as cloning, and allows large quantities of DNA corresponding to a gene of interest to be isolated and manipulated.
After the gene is isolated, the sequence of the nucleotide bases can be determined. The goal of the large-scale Human Genome Project is to sequence all the genes of several model organisms and humans. The sequence of the region containing the gene can reveal numerous features. If a gene is thought to encode a protein molecule, the genetic code can be applied to the sequence of bases determined from the cloned DNA. The application of the genetic code is done automatically by computer programs, which can identify the sequence of contiguous amino acids of the protein molecule encoded by the gene. If the function of a gene is unknown, comparisons of its nucleic acid or predicted amino acid sequence with the contents of huge international databases can often identify genes or proteins with analogous or related functions. These databases contain all the known sequences from many prokaryotic, archaeal, and eukaryotic organisms. Putative regulatory and transcript-processing sites can also be identified by computer. These putative sites, called consensus sequences, have been shown to play roles in the regulation and expression of groups of prokaryotic, archaeal, or eukaryotic genes. However, computer predictions are just a guide and not a substitute for analyzing expression and regulation by direct experimentation. See Genetic engineering, Human Genome Project, Molecular biology
elementary unit of heredity representing a piece of a molecule of deoxyribonucleic acid, or DNA (in some viruses, ribonucleic acid, or RNA). Each gene determines the structure of one of the proteins of a living cell, thereby participating in the formation of a character or trait of the organism. The aggregate of genes, the genotype, carries genetic information about all the species and individual characteristics of the organism. It was demonstrated that in all the organisms on earth (including bacteria and viruses) heredity is coded in the sequence of nucleotides of the genes. In the higher (eucaryotic) organisms, genes are part of special nucleopro-tein structures, the chromosomes. The main function of genes—programming the synthesis of enzymic and other proteins, carried out with the participation of cellular RNA (messenger RNA, ribosomal RNA, and transfer RNA)— is determined by their chemical structure (sequence of oxyribonucleotides—the elementary units of DNA). Change in the structure of a gene (mutation) disrupts certain biochemical processes in the cells, resulting in an intensification, weakening, or loss of previously existing reactions or characters.
The first proof of the actual existence of genes was obtained by the founder of genetics G. Mendel in 1865 while he was studying plant hybrids whose original forms differed in one, two, or three characters. Mendel concluded that every character must be determined by hereditary factors transmitted from parents to offspring with the gametes and that these factors are not divided in crosses but are transmitted as a whole and independently of one another. New combinations of hereditary factors and the characters determined by them may result from a cross. The frequency with which each combination appears can be predicted if one knows the hereditary behavior of the parents’ characters. This enabled Mendel to work out statistically probable quantitative laws describing the various combinations of hereditary factors in crosses.
The term “gene” was introduced by the Danish biologist W. Johannsen in 1909. In the last quarter of the 19th century it was conjectured that chromosomes play a major role in the transmission of hereditary factors, and in 1902-03 the American cytologist W. Sutton and the German scientist T. Boveri presented cytological proof that the Mendelian laws for the transmission and segregation of characters may be explained by the recombination of maternal and paternal chromosomes in crosses. The American geneticist T. H. Morgan began to elaborate the chromosomal theory of heredity in 1911. He showed that genes are situated on chromosomes and that the genes concentrated on a single chromosome are transmitted all together from parents to offspring, forming a single interlinked group. The number of interlinked groups is constant for any normal organism and is equal to the haploid number of chromosomes in its gametes. After it was demonstrated that in a crossing-over homologous chromosomes exchange pieces—blocks of genes—with each other, the different degrees of linkage between different genes became clear. Using the crossing-over phenomenon, Morgan and his co-workers began to analyze the intrachromosomal location of the genes and found that they are arranged in a linear fashion and that each gene occupies a definite place in the corresponding chromosome. By comparing the frequency and aftereffect of a crossing-over between different pairs, one can compile genetic maps of chromosomes that indicate precisely the relative position of the genes as well as the approximate distance between them. Such maps have been constructed for a number of animals (for example, Drosophila, housemice, chickens), plants (for example, corn and tomatoes), bacteria, and viruses. By simultaneously studying anomalous segregation of characters in the offspring and by studying cytologi-cally the structure of chromosomes in cells, one can compare structural abnormalities of individual chromosomes with changes in the characters of a given individual and find the position in the chromosome of the gene responsible for a particular character.
In the first quarter of the 20th century, the gene was described as an elementary, indivisible unit of heredity controlling the development of a single character, transmitted in toto in a crossing-over and capable of changing. Continued research (by such Soviet scientists as A. S. Serebrovskii, N. P. Dubinin, and I. I. Agol, 1929; N. P. Dubinin, N. N. Sokolov, and G. D. Tiniakov, 1934) revealed the complex structure and divisibility of the gene. In 1957 the American geneticist S. Benzer demonstrated in phage T4 the complex structure of the gene and its divisibility; he proposed the names cistron for a unit of function responsible for the structure of a single polypeptide chain, muton for a unit of mutation, and recon for a unit of recombination. There are many mutons and recons in a single functional unit (cistron).
By the 1950’s it was proven that DNA is the material foundation of genes in chromosomes. The English scientist F. Crick and the American scientist J. Watson (1953) elucidated the structure of DNA and advanced a hypothesis (later completely confirmed) about the mechanism of action of the gene. DNA consists of two complementary polynucleotide chains whose framework is formed by sugar and phosphate groups; one of four nitrogenous bases is linked to each sugar group. The chains are connected by hydrogen bonds arising between the bases. Hydrogen bonds can be formed only between strictly determined complementary bases: between adenine and thymine (AT pair) and guanine and cytosine (GT pair). This principle of pairing of bases explained how genetic information is transmitted exactly from parents to offspring, on the one hand, and from DNA to proteins, on the other.
Thus, gene replication is responsible for the preservation and unaltered transmission to offspring of the structure of the portion of DNA included in a given gene (autocatalytic function or property of autosynthesis). The capacity to assign the order of nucleotides in molecules of messenger RNA—the heterocatalytic function or property of heterosynthesis— determines the order in which the amino acids alternate in the proteins being synthesized. The messenger RNA molecule is synthesized in accordance with the rules of complementarity on the portion of DNA corresponding to the gene. When the messenger RNA attaches to ribosomes, it supplies the information needed for the correct arrangement of the amino acids in the protein chain under construction. The length of the gene is related to the length of the polypeptide chain being constructed under its control. A gene consists on the average of 1,000 to 1,500 nucleotides (0.0003-0.0005 mm). The American investigators S. Brenner and his co-workers (1964) and C. Yanofsky and his co-workers (1965) demonstrated that there is a strict correspondence (the so-called gene-protein colinearity) between the structure of the gene (alternation of nucleotides in DNA) and structure of the protein or, more precisely, polypeptide (alternation of amino acids in it).
A gene can change as a result of mutation, which can be defined in general as a disruption of the existing sequence of nucleotides in DNA. This change may be caused by the replacement of one pair of nucleotides by another pair (transversion and transition), loss of nucleotides (deletion), doubling (duplication), or shifting of a segment (translocation). There appear as a result new alleles that may be dominant or recessive or may manifest partial dominance. Spontaneous mutation of genes determines the genetic, or hereditary, variability of organisms and serves as material for evolution.
An important advance in genetics, one with great practical significance, was the discovery of induced mutagenesis, that is, artificial induction of mutation by radiation (the Soviet biologists G. A. Nadson and G. S. Filippov, 1925; the American geneticist H. Muller, 1927) and chemical agents (the Soviet geneticists V. V. Sakharov, 1933; M. E. Lobashev, 1934; S. M. Gershenzon, 1939; I. A. Rapoport, 1943; the Englishmen C. Auerbach and J. H. Robson, 1944). Mutations can be caused by a variety of substances (such as alkylating compounds, nitrous acid, hydroxy lamines, hydrazines, dyes of the acridine series, analogs of bases, and peroxides). Every gene mutates on the average in 1 out of 100,000 to 1,000,000 individuals in a single generation. The use of chemical and radiation mutagens sharply increases the frequency of mutations so that new mutations in a particular gene may appear in 1 out of 100 to 1,000 individuals per generation. Certain mutations are lethal, that is, they destroy the viability of the organism. For example, in cases where a protein loses its activity because of gene mutation, the individual ceases to develop.
In 1961 the French geneticists F. Jacob and J. Monod concluded that two groups of genes exist: structural genes, which are responsible for the synthesis of specific (enzymic) proteins, and regulatory genes, which control the activity of structural genes. The mechanism by which gene activity is regulated has been best studied in bacteria. Regulatory genes, or gene regulators, were shown to program the synthesis of special substances of a protein nature, the repressors. In 1968 the American investigators M. Ptashne, W. Gilbert, and B. Müller-Hill isolated in pure form the repressors of phage ? and the lactose operon of Escherichia coli. A small region of DNA, the operator, is situated at the very beginning of a series of structural genes. It is not a gene because an operator does not carry information about the structure of any protein or RNA. An operator is a region capable of specifically binding a protein-repressor as a result of which an entire series of structural genes can be temporarily blocked or inactivated. Still another element of the system regulating gene activity has been found—a promoter to which RNA-polymerase attaches. The structural genes of several enzymes that are linked by common biochemical reactions (enzymes of a single chain of consecutive reactions) are arranged next to each other in a chromosome. Such a block of structural genes and the operator and promoter, which control them and are next to them in the chromosome, form a single system, the operon. One molecule of messenger RNA can be “read” from one operon, whereupon the functions of the division of this messenger RNA into segments corresponding to the individual structural genes of the operon are performed during protein synthesis (in the course of translation). J. R. Beckwith and his co-workers (USA, 1969) isolated in pure form an individual gene of Escherichia coli, accurately determined its size, and photographed it in an electron microscope. H. Corana and his co-workers (USA, 1967-70) achieved the chemical synthesis of an individual gene.
The realization of the hereditary properties of a cell and of the organism is a very complex phenomenon. One gene can exert multiple action on the course of many reactions (pleiotropy); the interaction of genes (including genes found in different chromosomes) can alter the final expression of a character. Gene expression also depends on the external conditions that influence all the processes by which the genotype turns into the phenotype.
REFERENCESMolekuliarnia genetika, part 1. Moscow, 1964. (Translated from English.)
Bresler, S. E. Vvedenie v molekuliarnuiu biologiiu, 2nd ed. Moscow-Leningrad, 1966.
Lobashev, M. E. Genetika, 2nd ed. Leningrad, 1967.
Watson, J. D. Molekuliarnaia biologiia gena. Moscow, 1967. (Translated from English.)
Dubinin, N. P. Obshchaia genetika. Moscow, 1970.
Soifer, V. N. Ocherki istorii molekuliarnoi genetiki. Moscow, 1970.
N. P. DUBININ and V. N. SOIFER