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.

Testis single-cell RNA-seq reveals the dynamics ofde novogene transcription and germline mutational bias inDrosophila

“…It is likely that some of these substitutions would result in inviable offspring and would never be observed in an adult population. Our result suggests that mutational load varies between different cell divisions, consistent with previous work that suggests a variable lesion rate between cell types (Gao et al, 2011, 2014). Mutational load is the net product of damage and repair, and further characterization of how lesions occur and accumulate in the germline is needed to better understand the evolutionary ramifications of this process (Moorjani et al, 2016).…”

Genetic inviability is a major driver of type III survivorship in experimental families of a highly fecund marine bivalve

“…Sun & D. Hedgecock, unpublished data), active transposable elements (see below), and the large number and potential clustering of mutations arising during premeiotic cell divisions (Klekowski & Godfrey ; Gao et al . , ). The importance of premeiotic cell divisions for mutation accumulation is illustrated by molecular evidence for male‐driven evolution in mammals and birds, in which males have three‐ to six‐fold higher mutation rates than females (Ellegren & Fridolfsson ; Nachman & Crowell ; Makova & Li ).…”

“…Classical, mutation-drift, equilibrium theory, however, may overestimate the lethal mutation rate necessary to support the observed mutational load, because marine populations may be far from demographic and genetic equilibria, owing to variability in recruitment (Hjort 1914;Fogarty et al 1991;Cushing 1996;Myers 2001;Houde 2008) and sweepstakes reproductive processes (Hedgecock & Pudovkin 2011), in which a relatively small fraction of the spawning population may be responsible for the bulk of recruitment. Some features of oyster population biology that could increase the load but not necessarily the rate of lethal mutations or that could increase the variance in or initial frequency of lethal mutations include sweepstakes reproductive success, low effective population size (N e~1 50; Hedgecock 1994, Li & Hedgecock 1998, active trans-posable elements (see below), and the large number and potential clustering of mutations arising during premeiotic cell divisions (Klekowski & Godfrey 1989;Gao et al 2011Gao et al , 2014. The importance of premeiotic cell divisions for mutation accumulation is illustrated by molecular evidence for male-driven evolution in mammals and birds, in which males have three-to six-fold higher mutation rates than females (Ellegren & Fridolfsson 1997;Nachman & Crowell 2000;Makova & Li 2002).…”

Parent of Origin, Mosaicism, and Recurrence Risk: Probabilistic Modeling Explains the Broken Symmetry of Transmission Genetics

“…This advance might extend the application of Galton-Watson models and sampling results to other contexts in biology, such as population genetics or the emergence of mutations in model organisms that can be experimentally assayed. 29 We also developed an interesting result concerning the analysis of stochastic proportions. We showed that sampling a rare particle updates the expected proportion of that rare particle to the value determined by the size-biased distribution of the proportion.…”