Transgenerational genomic instability as revealed by a somatic mutation assay using the medaka fish

Abstract

We previously established a somatic mutation assay of the medaka wl ( white leucophores) locus based on visual inspection, and showed that somatic mutations at paternally derived alleles frequently arise during the development of F 1 embryos fertilized by sperm/late spermatids that had been exposed to γ-rays. To further study such delayed mutations, we determined the frequency of mutant embryos obtained from three different crosses between irradiated males and non-irradiated females. When sperm and late spermatids were irradiated, the mutant frequency within non-irradiated maternally derived alleles was ∼3 times higher than in the control group. In the F 2 generation, however, no increase in mutant frequency was observed. Similarly, there was no significant increase in the F 1mutant frequency when stem spermatogonia were irradiated. These data suggest that irradiation of sperm and late spermatids can induce indirect mutations in F 1 somatic cells, supporting the idea that genomic instability arises during F 1 embryonic development. Moreover, such instability apparently arises most frequently when eggs are fertilized just after the sperm are irradiated.