Population consequences of mutagenesis and antimutagenesis.

Abstract

Although the progress in basic understanding of mutagenesis and in techniques for precise measurement of mutation rates in test systems has been enormous, there has been very little progress in applying this information to estimates of germline mutation in humans, and even less in translating such estimates into quantitative assessments of the impact on future generations. This doesn't mean that new information about the mutation process, and antimutagens in particular, is not useful. Lowering the human mutation rate would be good, even if we can't say how good. Some simple population kinetics of a change of mutation are discussed, and it is shown that future environmental changes can be ignored if we assume that the impact of a disease on human welfare is changed by the environment in the same proportion as its effect on fitness. Since the human mutation rate appears to be much higher in males than in females, it would be especially important to find ways of reducing the male rate. The role of transposable elements in determining human spontaneous mutation rates is unknown, but unless data from experimental organisms are grossly misleading, this role may be substantial. It is sometimes argued that such responses as error-prone repair systems may be an evolutionary strategy to allow the population to try a larger repertoire of mutations in times of environmental change. They may also be a survival strategy. I suggest that, although such an evolutionary strategy may possibly be adopted in asexual organisms with a very high reproductive rate, it is very unlikely in Mendelian species with limited reproduction such as most higher animals. The amount of existing variability in a large population is so great relative to that which arises in a few generations by mutation that segregation and recombination of existing alleles would appear to be a better way of coping with changing environment. As the human age of reproduction has increased in the recent evolutionary past, it is possible that the compensatory adjustment of mutation rates has not been fast enough to keep up. Perhaps evolution of mutation rates is more determined by selection to reduce somatic mutation than by selection to reduce germinal mutation. Regardless of the answer to the question of the optimum mutation rate for long-time evolution, in my view, the optimum mutation rate from the standpoint of human welfare for the foreseeable future is zero.