Partial protection from cyclical selection generates a high level of polymorphism at multiple non-neutral sites

Temporally varying selection is known to maintain genetic polymorphism under certain restricted conditions. However, if part of a population can escape from selective pressure, a condition called the "storage effect" is produced, which greatly promotes balanced polymorphism. We investigate whether seasonally fluctuating selection can maintain polymorphism at multiple loci, if cyclically fluctuating selection is not acting on a subpopulation called a "refuge." A phenotype with a seasonally oscillating optimum is determined by alleles at multiple sites, across which the effects of mutations on phenotype are distributed randomly. This model resulted in long-term polymorphism at multiple sites, during which allele frequencies oscillate heavily, greatly increasing the level of nonneutral polymorphism. The level of polymorphism at linked neutral sites was either higher or lower than expected for unlinked neutral loci. Overall, these results suggest that for a protein-coding sequence, the nonsynonymous-to-synonymous ratio of polymorphism may exceed one. In addition, under randomly perturbed environmental oscillation, different sets of sites may take turns harboring long-term polymorphism, thus making trans-species polymorphism (which has been predicted as a classical signature of balancing selection) less likely.