Are mutations usually deleterious? A perspective on the fitness effects of mutation accumulation

Abstract

All adaptive alleles in existence today began as mutations, but a common view in ecology, evolution, and genetics is that non-neutral mutations are much more likely to be deleterious than beneficial and will be removed by purifying selection. By dramatically limiting the effectiveness of selection in experimental mutation accumulation lines, multiple studies have shown that new mutations cause a detectable reduction in mean fitness. However, a number of exceptions to this pattern have now been observed in multiple species, including in highly replicated, intensive analyses. We briefly review these cases and discuss possible explanations for the inconsistent fitness outcomes of mutation accumulation experiments. We propose that variation in the outcomes of these studies is of interest and understanding the underlying causes of these diverse results will help shed light on fundamental questions about the evolutionary role of mutations.

Mutation bias alters the distribution of fitness effects of mutations

“…As discussed previously by us and by others, such high f b values are not as rare as generally believed, especially during mutation accumulation studies [11,35]. In a recent review, Bao and colleagues suggest that the widely variable outcomes of fitness decline in MA lines (an indicator of the proportion of deleterious vs. beneficial mutations) is not easily explained by organism, genetic background, or test environment, but may arise from complex interactions between these and/or other factors [35]. In our current study, we ruled out several mechanisms that could artificially inflate the observed f b values: selection bias during MA (we corrected our DFEs for such bias [15]), low ancestral fitness leading to high f b values [27,28,36] (we did not find a correlation between ancestral fitness and f b ), and the impact of specific strain backgrounds (we observe a general effect of Ts vs. Tv mutations on f b ).…”

Fitness effects of somatic mutations accumulating during vegetative growth

“…It is striking that high rates of beneficial mutation accumulation have been observed in at least some mutation accumulation studies in the autogamous plant Arabidopsis thaliana (Rutter et al 2012(Rutter et al , 2018(Rutter et al , 2010Shaw et al 2002), but not in outcrossing and partially-selfing species of Amsinckia (Schoen 2005). With a few exceptions (e.g., Baer et al 2005;Denver et al 2010), nearly all mutation accumulation studies on animals consistently show a prevalence of deleterious mutations (Baer et al 2007;Halligan and Keightley 2009; but see Bao et al 2022). Our results suggest that the adaptive potential of autogamous plants may be greater than previously thought, which may help explain the wider geographic ranges of selfing compared to closely-related outcrossing species (Grant and Kalisz 2020;Grossenbacher et al 2015).…”

Gene Birth in a Model of Non-genic Adaptation

“…Many studies report the abundance of deleterious mutations compared to beneficial mutations, but there is plenty of evidence to the contrary as well [56]. We do not have extensive empirical measurements of the DFE of non-genic loci, nevertheless, since these loci are not expected to be expressed at high levels, it makes intuitive sense to assume that most non-genic mutations should be nearly neutral.…”