Epigenetic Control Systems.

Advances in chemical genetics in the past few years have permitted the formulation of a consistent hypothesis concerning the chemical nature of the "primary" genetic material.1 This material is considered to consist of nucleic acid (usually deoxyribosenucleic acid) and to contain genetic information in a code of prescribed nucleotide sequences. The information is believed to be preserved during replication by a "semiconservative" reproductive mechanism, whereby each daughter strand retains a half of the parental molecule and reconstructs a complementary portion. Alterations in the genetic material are thought to come about in one of two major fashions. Mutations are the more or less random alterations in the code which result from chance substitutions in the nucleotide sequences or from gains or losses of nucleotides. Recombination also results in changes in the code, but these changes are achieved in a more orderly fashion; they require the physical association of different kinds of genetic material and are limited in their possibilities in any given instance by the nucleotide sequences in the parental materials. According to this hypothesis, the genetic material expresses its specificity through a decoding process, by which the information in the nucleotide sequences is eventually translated into, for example, amino acid sequences in proteins. This view of the nature of the genetic material, while certainly not established in detail, finds much support in experimental studies and gains great strength from its simplicity. It permits, moreover, a clearer conceptual distinction than has previouslybeen possible between two types of cellular control systems. On theone hand, the maintenance of a "library of specificities," both expressed and unexpressed, is accomplished by a template replicating mechanism. On the other hand, auxiliary mechanisms with different principles of operation are involved in determining which specificities are to be expressed in any particular cell. Even without specifying precisely how these other mechanisms operate, the distinction between mechanisms involving template replication and "other mechanisms" is reasonably clear, even though both are involved in determining cellular characteristics. Difficulties arise, however, when one attempts to determine whether observed differences in cellular properties are due to differences in the "primary genetic material" or to differences in other cellular constituents. Some of these difficulties can be made apparent by setting forth certain general propositions related to the supplementary regulatory systems for which evidence is now available. To simplify the discussion of these two types of systems, they will be referred to as "genetic systems" and "epigenetic systems." The term "epigenetic" is chosen to emphasize the reliance of these systems on the genetic systems and to underscore their significance in developmental processes.2 1. Cells with the Same Genetic Material May Manifest Different Phenotypes.Although this proposition cannot be directly demonstrated to be true, abundant circumstantial evidence for its validity is available. Certainly, microbial cells grown on different substrates or cells found in different tissues of a higher organism