Pattern of mutation rates in the germline of Drosophila melanogaster males from a large-scale mutation screening experiment

Abstract

The sperm or eggs of sexual organisms go through a series of cell divisions from the fertilized egg; mutations can occur at each division. Mutations in the lineage of cells leading to the sperm or eggs are of particular importance because many such mutations may be shared by somatic tissues and also may be inherited, thus having a lasting consequence. For decades, little has been known about the pattern of the mutation rates along the germline development. Recently it was shown from a small portion of data that resulted from a large-scale mutation screening experiment that the rates of recessive lethal or nearly lethal mutations differ dramatically during the germline development of Drosophila melanogaster males. In this paper the full data set from the experiment and its analysis are reported by taking advantage of a recent methodologic advance. By analyzing the mutation patterns with different levels of recessive lethality, earlier published conclusions based on partial data are found to remain valid. Furthermore, it is found that for most nearly lethal mutations, the mutation rate at the first cell division is even greater than previous thought compared with those at other divisions. There is also some evidence that the mutation rate at the second division decreases rapidly but is still appreciably greater than those for the rest of the cleavage stage. The mutation rate at spermatogenesis is greater than late cleavage and stem-cell stages, but there is no evidence that rates are different among the five cell divisions of the spermatogenesis. We also found that a modestly biased sampling, leading to slightly more primordial germ cells after the eighth division than those reported in the literature, provides the best fit to the data. These findings provide conceptual and numerical basis for exploring the consequences of differential mutation rates during individual development.

Keywords: Drosophila melanogaster; cell coalescent; germline mutation rate; likelihood inference.

Figure 1

Population dynamics and an example of the genealogy of four sperm sampled at the time at which maximal 38th cell division has occurred (adapted from Fu 2013).

Figure 2

Distribution of family sizes in 9594 screened families.

Figure 3

Distribution of the percentage of z/z offspring among 271,794 lines in F₃.

Figure 4

Cross and results for family 140. a/b (e.g. 0/101) beside a line indicates the numbers of z/z and total offspring of the cross, respectively. Three crosses, between lines 19 and 30, between 12 and 24, and between lines 1 and 3 are individually significant (with * and *** representing, respectively, significance at 5 and 1% level). After adjusting for multiple tests, all three crosses are significant at the 50% significance level but only the cross between lines 1 and 3 remains significant at the 10% significance level.

Figure 5

Mean minimum percentage of z/z offspring among nontested lines in windows of 200 families.