Mildly deleterious mutations (MDMs) with incomplete dominance, which decrease the viability of the progeny, apparently play a significant role in the evolution of sexual reproduction. In particular, they are thought to be eliminated in meiosis. The nature of MDM remains unclear. By studying the accumulated MDMs in Drosophila strains carrying various meiotic mutations (c(3)G17, mei-P22, mei-W68, mei-41, mei-218), we found that impair the formation of DNA breaks is more effective in accumulation of MDMs. The relationship between survival and generation number upon MDMs accumulation suggests that MDMs interaction corresponds to their synergistic epistasis. The viability in progeny after meiosis in heterozygotes with chromosome with accumulated MDMs and normal chromosome, and in heterozygotes with independently accumulated MDMs chromosomes was shown to be restored. Our results support the hypothesis that MDMs have epigenetic nature. It is proposed that: during the life cycle “mutant” variants of the formation of structural and functional loop domains appear in the chromosomes; these variants are normally corrected in meiosis; an abnormal loop alters the activity of many genes (~17), increasing (+) or decreasing (–) it. The hybrids with chromosomes carrying independently accumulated MDMs partially restore viability due to complementary interaction of + and – genes.