Causes of variability in estimates of mutational variance from mutation accumulation experiments

Abstract

ABSTRACTCharacteristics of the new phenotypic variation introduced via mutation have broad implications in evolutionary and medical genetics. Estimates of this mutational variance, VM, span two orders of magnitude, but factors contributing to this range remain poorly resolved. We applied meta-analyses to ∼200 estimates from 62 studies to assess how previously implicated factors affect the magnitude of VM. While estimates are available from a range of taxa, and quantitative trait types over a range of timescales, these factors are confounded with one another. We call for further directly comparable empirical data to resolve these influences on variability of VM. We also analysed data from Drosophila serrata lines, derived from a mutation accumulation experiment, observing substantial heterogeneity among replicated estimates of among-line variance for 11 morphological (wing) traits. Micro-environmental variation in mutational effects was implicated as causing variability in mutational variance for just two of 11 traits, suggesting estimation environment may contribute little to variability of published estimates. Varying the opportunity for evolutionary processes to increase within-line genetic variation did not affect among-line variance estimates, suggesting transient segregation of mutations is also an unlikely general explanation of variability in published estimates. We conclude that estimation error, expected to be relatively high due to the low differentiation among lines diverging solely through new mutation, is likely to contribute strongly to variability of estimates of mutational variance. Analyses of repeated measures of mutation accumulation lines can improve the precision of estimates, consequently expanding our understanding of the dynamics of mutations in natural populations.