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The Mechanics Of Heredity - Factors In Behavior

chromosomes genes pair gene example process cell genetic cells traits

A concept of the mechanical basis of heredity is necessary for an understanding of the rest of this chapter. The student is referred to a standard textbook for important details, but a brief resume follows.

Each mature human spermatozoan and ovum contains 23 structurally distinct chromosomes. Each chromosome consists of hundreds of genes - the functionally distinct regions which constitute the building blocks or basic units of heredity. The union of sperm and egg (zygote) at fertilization results in a new cell with a total of 46 chromosomes. These are arranged in 23 pairs of matched or homologous chromosomes, one member of each pair from the mother and the other from the father. The linear arrangement or order of genetic regions in two corresponding chromosomes is believed to be identical with a few exceptions, for example, the pair of chromosomes determining the sex of the individual. Thus, the corresponding genes of a chromosome pair (alleles) are of similar chemical composition and subserve similar functions. They may not be identical, however, since they are derived from different parents.

As the cells of the body multiply from fertilization until death, genes have the property of producing exact replicas of themselves out of raw material presented to them within the cells. After this process is complete and all the genes along all the chromosomes have been replicated, the cell divides, forming two new cells each of which again has 23 pairs of chromosomes and its complements of genes (mitosis).

There is one exception to this process, however. These are the cells which, through differentiation, are to become the sperm or ova of the new individual. These must contain only one set of chromosomes for the process of fertilization and mixture of maternal and paternal chromosomes to continue in succeeding generations. This is accomplished by a failure of replications of the chromosomes before cell division takes place, thus reducing the number of chromosomes from 46 to 23 again (meiosis). In this process there is equal probability that chromosomes originally derived from the father or the mother will fall into a given daughter cell. This process is called segregation. Thus the egg or sperm cell contains some chromosomes derived from the father and some from the mother, generally distributed in a random fashion. However, there is another process which adds to the randomness of the shuffling of the hereditary cards. Before the chromosomes of the maturing germ cell separate, a process called crossing-over may occur. A break occurs at corresponding points in two homologous chromosomes and, in crisscross fashion, corresponding segments of a pair of chromosomes exchange places. In this way shuffling occurs among the genes themselves as well as among intact chromosome units. It is this shuffling of the genetic material through segregation and recombination which accounts for the enormous differences among the offspring of given parents and for biologic variation in the species in general.

Some hereditary defects can be understood in terms of the shuffling of a single gene pair in the maturation of germ cells. For example, certain kinds of muscular dystrophy are believed to be the result of a change (mutation) in a single gene of an allele pair. Every descendant receiving the defective gene will develop dystrophy traits. Traits of this type are said to be Mendelian dominant. In other instances it is necessary for both alleles of a pair to contain the defective gene. Such traits are called Mendelian recessive traits. An example of this is phenylpyruvic oligophrenia, a type of mental deficiency associated with metabolic abnormalities. In many diseases, however, the situation is more complex. More than one allele pair may be involved, and there may be interaction with other genetic as well as environmental factors. Thus the appearance or nonappearance of the defect may be complexly determined. Pairs of genes sub-serving different traits which are located close together on the same chromosome will have greater than average chance of being transmitted together. In other words, certain traits tend to be linked to one another. An example of this phenomenon are traits or defects whose genes are located on the chromosomes associated with the determination of sex. The blood disease hemophilia is an example of a sex-linked condition.

Chemically, genes are thought to be complex macromolecules of desoxyribonucleic acid (DNA). Pauling and Delbruck (13) have proposed a two-stage mechanism by which genes duplicate themselves. Gene A serves as the template for the synthesis of a complementary molecule A-1. This in turn serves as the template for the manufacture of its complementary molecule, which is identical with A.

Probably by a related mechanism genes serve also as templates for the synthesis of ribonucleic acid molecules (RNA), which in turn are the templates for the synthesis of amino acids in the cytoplasm. The latter are the building blocks of all proteins. Thus genes exert their influence by their effect on biochemical reactions.

In recent years the notion has been advanced that a one-to-one relationship exists between genes and enzymes; that is, for every gene there corresponds a specific enzyme and hence a specific chemical reaction under its control. In this way a specific gene abnormality may lead to a specific enzymatic defect. The metabolic abnormality which results may be of no great consequence to the physiology of the organism. On the other hand, it may lead to serious disease. An example of this is sickle cell anemia which is believed to be due to a single abnormal gene. The abnormal enzyme that results produces an abnormal hemoglobin molecule which is presumed to account for the abnormal shape of the red cells and the anemia which results. Such diseases have been called molecular, indicating that they have at their root a specific genetic, and hence enzymatic, abnormality. Another example is the disease phenylpyruvic oligophrenia mentioned previously. Here both genes of the allele pair must be defective, leading eventually to the absence of the enzyme normally present which converts the amino acid, phenylalanine, into tyrosine. As a result, the phenylalanine is metabolized to phenylpyruvic acid, which is excreted in the urine. The mental deficiency is related to these metabolic abnormalities.

The vast majority of times, the genes produce identical replicas of themselves. At infrequent intervals, however, changes occur in the chemical structure of genes in the process of duplication. These are mutations. They occur rarely but with increasing frequency when the cells are exposed to certain kinds of chemical or physical stimulation, e.g., radiation. Again the vast majority of slight mutations are probably trivial and of no importance to the organism. However, they may lead to enzymatic and hence structural and physiologic changes. Thus we have another way in which the genetic mechanism can go awry and lead to disease and abnormality. An example of this is epiloia (tuberous sclerosis), a rare disease in which there is mental deficiency, epilepsy, and multiple benign tumors of the brain, kidney, and other tissues. It is believed that about one case in four is due to a mutation, the remainder being the direct inheritance of a dominant gene (7).

In the above examples of genetically determined mental defect there are gross structural and biochemical changes which can be identified. It is likely, however, that more subtle structural and biochemical variations occur with greater frequency in the population as the result of the constant reshuffling of genes and constant mutations. Since all human behavior and psychologic functioning have their ultimate basis in the body, it is possible that a great variety of disorders of behavior and abnormal mental states have their basis, in part, in genetic variation. Indeed, evidence has been growing for the role of genetic factors in a great variety of psychologic and behavioral disturbances. By their nature, however, the development and manifestations of psychologic disturbances are greatly influenced by environmental factors which make more difficult the identification of their hereditary components.

The question of the operation in man of hereditary mechanisms other than the chromosomal system of the nucleus has recently been raised. Cytoplasmic inheritance has been observed to occur in one-celled organisms, e.g., paramecia. However, an extra-chromosomal cytoplasmic system has not been directly observed in higher animals and it is unlikely that such a system, if it exists, compares in importance with the chromosomal inheritance in the nucleus (12, 19).

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