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

Abstract

Characteristics of the new phenotypic variation introduced via mutation have broad implications in evolutionary and medical genetics. Standardised estimates of this mutational variance, VM, span two orders of magnitude, but the causes of this remain poorly resolved. We investigated estimate heterogeneity using two approaches. First, meta-analyses of ~150 estimates from 37 mutation accumulation (MA) studies did not support a difference among taxa (which differ in mutation rate) in standardised VM, but provided equivocal support for standardised VM to vary with trait type (life history versus morphology, predicted to differ in mutation rate). Notably, several experimental factors were confounded with taxon and trait, and further empirical data are required to resolve their influences. Second, we analysed morphological data from an experiment in Drosophila serrata to determine the potential for unintentional heterogeneity among environments in which phenotypes were measured (i.e., among laboratories or time points) or transient segregation of mutations within MA lines to affect standardised VM. Approximating the size of an average MA experiment, variability among repeated estimates of (accumulated) mutational variance was comparable to variation among published estimates of standardised VM for morphological traits. This heterogeneity was (partially) attributable to unintended environmental variation or within line segregation of mutations only for wing size, not wing shape traits. We conclude that sampling error contributed substantial variation within this experiment, and infer that it will also contribute substantially to differences among published estimates. We suggest a logistically permissive approach to improve the precision of estimates, and consequently our understanding of the dynamics of mutational variance of quantitative traits.