Increased transmission of mutations by low-condition females: evidence for condition-dependent DNA repair

Abstract

Evidence is mounting that mutation rates are sufficiently high for deleterious alleles to be a major evolutionary force affecting the evolution of sex, the maintenance of genetic variation, and many other evolutionary phenomena. Though point estimates of mutation rates are improving, we remain largely ignorant of the biological factors affecting these rates at the individual level. Of special importance is the possibility that mutation rates are condition-dependent with low-condition individuals experiencing more mutation. Theory predicts that such condition dependence would dramatically increase the rate at which populations adapt to new environments and the extent to which populations suffer from mutation load. Despite its importance, there has been little study of this phenomenon in multicellular organisms. Here, we examine whether DNA repair processes are condition-dependent in Drosophila melanogaster. In this species, damaged DNA in sperm can be repaired by maternal repair processes after fertilization. We exposed high- and low-condition females to sperm containing damaged DNA and then assessed the frequency of lethal mutations on paternally derived X chromosomes transmitted by these females. The rate of lethal mutations transmitted by low-condition females was 30% greater than that of high-condition females, indicating reduced repair capacity of low-condition females. A separate experiment provided no support for an alternative hypothesis based on sperm selection.

Figure 1. Crossing Design for Detection of Sex-Linked Recessive Lethal Mutations

In the parental cross, high- or low-condition females of genotype Basc/X were mated to wild-type males who had been mutagenized with MMS. From each mother, four to ten F₁ daughters were placed in individual vials to lay eggs. Each of these daughters carried a paternally inherited (mutagenized) X chromosome, denoted as X_i in grey. These females had been allowed to mate with their brothers, which means they could have mated to either X/Y or Basc/Y males though offspring arrays indicate that it was usually the former as depicted here. Regardless of the F₁ male, 25% of the F₂ offspring are expected to be X_i / Y (wild-type) males (shown in dashed box). However, if there is a recessive lethal (or near lethal) on X_i, then X_i / Y males will be absent or very rare. We attempted to classify each X_i as carrying a (near) lethal or as not doing so, depending on the likelihood of obtaining the observed frequency of X_i / Y males when the expected frequency was 25% (no lethal) relative to the likelihood when the expected frequency was 2.5% (near lethal). If there was not sufficient evidence from the distribution of F₂ progeny to classify an X_i in either of these two categories, then that X_i was excluded from further analysis. See Materials and Methods for details.