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Can Synergistic Epistasis Halt Mutation Accumulation? Results from Numerical Simulation by:1 (Source: Crossref)

    The process of deleterious mutation accumulation is influenced by numerous biological factors, including the way in which the accumulating mutations interact with one another. The phenomenon of negative mutation-to-mutation interactions is known as synergistic epistasis (SE). It is widely believed that SE should enhance selective elimination of mutations and thereby diminish the problem of genetic degeneration. We apply numerical simulation to test this commonly expressed assertion.

    We find that under biologically realistic conditions, synergistic epistasis exerts little to no discernible influence on mutation accumulation and genetic degeneration. When the synergistic effect is greatly exaggerated, mutation accumulation is not significantly affected, but genetic degeneration accelerates markedly. As the synergistic effect is exaggerated still more, degeneration becomes catastrophic and leads to rapid extinction. Even when conditions are optimized to enhance the SE effect, selection efficiency against deleterious mutation accumulation is not appreciably influenced.

    We also evaluated SE using parameters that result in extreme and artificially high selection efficiency (truncation selection and perfect genotypic fitness heritability). Even under these conditions, synergistic epistasis causes accelerated degeneration and only minor reductions in the rate of mutation accumulation.

    When we included the effect of linkage within chromosomal segments in our SE analyses, it made degeneration still worse and even interfered with mutation elimination. Our results therefore strongly suggest that commonly held perceptions concerning the role of synergistic epistasis in halting mutation accumulation are not correct.