Alternatively, we can ask how evolution within a population affects the mutation rate. This can be done by postulating a locus that affects the mutation rate of other genes. This locus might, for example, encode a DNA repair enzyme. For simplicity, let us assume that alleles at this locus do not differ in their direct effect on the fitness of their bearers – they do not directly affect survival or reproduction. They have only an indirect effect via mutations they allow or prevent. Such a locus is often called a MODIFIER of mutation, and the action of natural selection on such a locus is termed SECOND-ORDER SELECTION. Models of second-order selection on modifier loci are the most useful devices for understanding the evolution of genetic systems.