  A model of mutation rate evolution for multiple loci under arbitrary
selection is analyzed. Results are obtained using techniques from Karlin (1982)
that overcome the weak selection constraints needed for tractability in prior
studies of multilocus event models. A multivariate form of the reduction
principle is found: reduction results at individual loci combine topologically
to produce a surface of mutation rate alterations that are neutral for a new
modifier allele. New mutation rates survive if and only if they fall below this
surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994)
for a multilocus recombination modifier. Increases in mutation rates at some
loci may evolve if compensated for by decreases at other loci. The strength of
selection on the modifier scales in proportion to the number of germline cell
divisions, and increases with the number of loci affected. Loci that do not
make a difference to marginal fitnesses at equilibrium are not subject to the
reduction principle, and under fine tuning of mutation rates would be expected
to have higher mutation rates than loci in mutation-selection balance. Other
results include the nonexistence of 'viability analogous, Hardy-Weinberg'
modifier polymorphisms under multiplicative mutation, and the sufficiency of
average transmission rates to encapsulate the effect of modifier polymorphisms
on the transmission of loci under selection. A conjecture is offered regarding
situations, like recombination in the presence of mutation, that exhibit
departures from the reduction principle. Constraints for tractability are:
tight linkage of all loci, initial fixation at the modifier locus, and mutation
distributions comprising transition probabilities of reversible Markov chains.
