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The functioning of genes (hereditary units) in determining the structural and functional characteristics of an individual, that is, its phenotype. Gene action is studied by two somewhat different, but complementary, approaches: (1) the analysis of changes which occur in the phenotype when a gene mutates, or is changed in dosage, or in position relative to other genes; this is frequently called the study of phenogenetics; and (2) the more direct approach, which attempts to determine the actual means by which genes exert their control over metabolism and the processes of development in multicellular, differentiated organisms. The more direct approach is best described as study of primary gene action, but includes study of the interaction of primary or secondary products of gene action. See Gene
All genes, with the exception of those in ribonucleic acid (RNA) viruses, are constituted of deoxyribonucleic acid (DNA), and the primary action of the great majority of them is to initiate a series of events leading directly or indirectly to the determination of the amino acid sequences of specific polypeptides. See Deoxyribonucleic acid (DNA), Protein, Virus
The base sequence of one of the chains of the DNA double helix constituting the gene is transcribed into an RNA molecule with a chain of complementary bases in the presence of RNA polymerases. This RNA molecule may then frequently become a messenger RNA (mRNA) by some alteration of the original transcript, or it may become a transfer RNA (tRNA) or a ribosomal RNA (rRNA). See Ribonucleic acid (RNA)
The primary action of a gene is transcription, but the expression of this action lies in the next step—translation—for many genes. The mRNAs are translated into polypeptides in what may be considered the culmination of the primary process of gene action. The proteins so formed may act as enzymes, structural units, regulators of various metabolic processes by interacting with other proteins and genes, and essential agents in guiding and directing the processes of development.
The actual effects of gene action are recognized for the most part by noting the effects of gene mutation on the phenotype, but in complex multicellular organisms the final phenotypic effect observed superficially may be far removed from the initial action of the gene itself, for example, a change in shape of the ear or a change in eye color. Studies of a wide variety of different genetic strains of organisms ranging over phages and bacteria, plants and animals, including humans, have shown that the mutations of some genes are reflected in the qualitative alteration of the proteins they code for. These kinds of genes are called structural genes. Frequently the protein changes resulting from their mutation are simple substitutions of a single amino acid in the chain by another. The cause for this substitution can be traced back to a change in the genetic code. If a codon in the DNA of a gene coding for a specific polypeptide is altered by a base, for example, AAA → CAA, this mutation will result in the substitution of valine for the phenylalanine originally present at the specific site in the polypeptide chain coded for by this codon. A protein so changed, even though it may involve only one amino acid residue out of more than 100, may have no noticeable effects on the phenotype, or it may have drastic effects. See Genetic code
If there is no noticeable effect of mutation on a protein's action in forming the phenotype, the mutant allele may be called a neutral allele. However, even a single amino acid substitution may cause a protein to be completely inactive and, if the protein is an enzyme, create a genetic metabolic block. Over 100 different inherited blocks are known in humans, including phenylketonuria. The mutant protein may also be active, but its activity is altered so that it is less active than the wild type, or more active, or only active at certain temperatures or pH, or may be inhibited by substances not inhibitory to the wild-type enzyme. The range of possible effects is considerable, and by no means are all recognized and cataloged.
Some genes code for RNA that is not translated. The obvious ones are those that code for tRNA and rRNA, but other RNAs are also transcribed that do not appear to be transcribed and may have a role in the regulation of the activity of other genes. Finally, some genes code for proteins that act as regulators of the processes of metabolism and development. As yet, little is known about this class of genes in the eukaryotes, but they have been studied intensively in bacteria and phages. Mutations of genes coding for regulators may have profound effects on the course of development and, if they do not cause early lethality, they may result in the birth of a malformed individual. See Bacterial genetics, Operon
Under certain conditions, an increase in the number of times a particular gene is present has a direct quantitative effect on one or more aspects of the phenotype. This effect is considered to be a manifestation of quantitative gene activity or gene dosage. It means that the gene does something, and that the higher the dose with which it is present, the greater the physiological or chemical end result. The best examples of this are found in the genetics of polyploid plants. In these plants, it is possible to increase the dosage of a particular allele from zero to four or more, when this is done, for example, with certain genes which control the production of the flower pigments of Dahlia, there is a demonstrable increase in the amount of pigment in the petals. See Polyploidy
An increase in the dose of an active allele of a gene does not always cause an increase in the manifestation of a particular aspect of the phenotype. It may have quite the opposite effect, and cause a decrease. Plants and animals are also subject to aneuploidy, in which not all of the chromosomes of the genome are increased in number proportionately. Instead, only one of the chromosomes of the diploid set may be increased or decreased in number. In humans these conditions usually lead to the early death of the embryo. If the fetus reaches term and is born, it is always abnormal. A relatively common occurrence in humans is trisomy-21, which leads to Down syndrome. See Down syndrome
Some heterozygous combinations of mutant alleles do not produce the phenotype expected from the phenotypes of the homozygotes. This is defined as a manifestation of allelic interaction. It is in contrast to those situations in which one allele is dominant over the other, so that the phenotype of the heterozygote is very similar or identical to that of the homozygous dominant. Also, it is different from those situations in which the two alleles show an additive effect, and the phenotype of the heterozygote is intermediate between those expected from the homozygotes. Diploid organisms heterozygous for two mutant alleles will produce two polypeptide species, one for each allele. The two proteins may interact and form hybrid multimers, which may be more or less active than the homomultimers formed by the polypeptides of each of the two genes alone. See Dominance
The final phenotype of an organism is the resultant of the action of all the active genes in its cell or cells. These genes may act independently in producing their respective primary products, but the primary products, and the products of their activity, that is, enzymes and other macromolecules, interact at the level of extragenic metabolism to give the final phenotype. Thus, there is really no one gene determining the shape of an organ, or even the production of a certain pigment. These end products are determined by many genes acting together through their respective immediate and then succeeding interrelated products. The manifestation of these interactions, as determined initially by the results from breeding experiments and in a few cases from biochemical analysis, is called gene interaction. This term does not necessarily imply that the genes themselves interact. In general, the term is applied to apparent interactions between genes. Examples include: complementary genes, in which nonallelic genes are so directly involved in the formation of the same end product, or phenotype, that the mutation of any one of them to an inactive state will result in no end product or type effect; epistasis, in which one gene masks the effects of other genes that may be present; and suppressor genes, which cause a wild-type or normal phenotype despite the presence of nonallelic mutant genes.
The environment must be considered in any analysis of gene action, if it is desired to arrive at an understanding of how genes act toward the production of the phenotype. Practically, this is best done by keeping the environment as constant as possible while making studies of gene action. However, much also can be learned by varying the environmental conditions and keeping the genotype as constant as possible. See Genetics
The environment of genes is a complex one. For convenience, two areas can be defined: (1) that immediately around the genes, the intracellular environment of the rest of the cell; and (2) the extracellular and extraorganismal environment. The intracellular environment can be changed by the mutation of other genes, which may then modify the action of a gene under study. Gene interaction is thus seen to be in part an aspect of the study of the internal environment of the cell. Extracellular environmental factors, such as light and heat, may also influence the action of genes greatly.
Changes in phenotype which occur against a constant genetic background are in reality responses to the environment by the extragenic part of the living system. The genes themselves are not changed, as can be readily demonstrated by changing the environment back to the original condition, or by breeding the individual and showing that the offspring inherit the original parental genotype. See Developmental genetics, Gene