THE IMPORTANCE OF MUTATION RATE GENES IN EVOLUTION

One of the problems of longest interest in genetics and evolution is the spontaneous appearance of gene changes, mutations. It is only within the past thirteen years that it has been clearly shown that the rate of spontaneous mutation depends in part at least upon the genotype of the individual and that certain individual genes are themselves capable of causing marked changes in this rate. (See particularly Demerec, 1927 a, b-; Neel, 1942; Mampell, 1943; Ives, 1945.) The mechanism by which mutagenic agents work-whether they be physical, chemical or genetic agent-s-is still essentially unknown. It is important, therefore, to report studies on any level showing the kinds and quantities of mutations produced by a given agent under specified conditions. It is particularly interesting to report such studies on a genetic agent derived directly from a natural population. Presumably this type of agent is a major source, possibly the major contributor, of new mutations in wild populations. Students of genetics generally recognize that such an agent may play a role of exceptional importance in organic evolution. The origin of the mutator under consideration and some preliminary studies on it have been presented in Ives (1945). Other studies have appeared in abstract form in Ives (1943,1947, 1949) and in Ives and Andrews (1946). The major aim of these studies andthe present report is' to show something of what the gene in question does genetically and to discuss the evolutionary significance of these observations. In two of the earlier studies on mutators the genes were lost within a year or two after their first discovery, for reasons not clearly demonstrated. It seemed more valuable, therefore, to attack the mutagenic properties of the present mutator at once rather than to determine the exact chromosome locus involved. As it turns out, since the gene's mutagenic properties are so complex and since only by its ability to raise the mutation rate is the gene phenotypically recognizable, it will be a task of considerable difficulty to determine even roughly its locus. However, since the gene is now successfully balanced with marked chromosomes, the problem of its exact locus is of minor importance. This mutator gene has been named high (hi). The studies completed so far with hi have been particularly designed to show what hi could contribute genetically to a given wild population of Drosophila melavnogaster, as regards gene mutations and chromosome rearrangements, under different controlled genetic and environmental conditions. Specifically, they have measured the rate and variety of second chromosome lethal mutations, of X-chromosome lethal and easily noticeable visible mutations, and of X-chromosome inversions when these are associated with sexlinked lethal or visible mutations. In some of these experiments hi was homozygous; in others, heterozygous. In some cases the mutations arose in sperm deposited by young males; in others, in sperm deposited by males aged up to four weeks. Taken together these studies show the following facts. First, hi affects the mutation rate of many genes, but not all of them with equal frequency. It increases the general mutation rate up to ten times the normal rate. Second, whether it acts as a dominant or a recessive appears to.