Direct inference of the distribution of fitness effects of spontaneous mutations inChlamydomonas reinhardtii

Abstract

Spontaneous mutations are the source of new genetic variation and are thus central to the evolutionary process. In molecular evolution and quantitative genetics, the nature of genetic variation depends critically on the distribution of fitness effects (DFE) of mutations. Spontaneous mutation accumulation (MA) experiments have been the principal approach for investigating the overall rate of occurrence and cumulative effect of mutations, but have not allowed the effects of individual mutations to be studied directly. Here, we crossed MA lines of the green alga Chlamydomonas reinhardtii with its unmutated ancestral strain to create haploid recombinant lines, each carrying an average of 50% of the accumulated mutations in a variety of combinations. With the aid of the genome sequences of the MA lines, we inferred the genotypes of the mutations, assayed their growth rate as a measure of fitness, and inferred the DFE using a novel Bayesian mixture model that allows the effects of individual mutations to be estimated. We infer that the DFE is highly leptokurtic (L-shaped), and that a high proportion of mutations increase fitness in the laboratory environment. The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution. Specifically, such a distribution predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size.

Fitness effects of mutation in natural populations of Arabidopsis thaliana reveal a complex influence of local adaptation

“…The distribution of French MA line fitness relative to their French founders in France and Swedish MA line fitness relative to their Swedish founders in Sweden indicates a high proportion of beneficial mutations when mutations arise in the environment where they would naturally be found, the home environment. Although our finding of frequent beneficial mutations in the field is surprising in light of evidence for predominantly deleterious mutations in many studies (e.g., Bataillon 2003;Keightley and Lynch 2003;Eyre-Walker and Keightley 2007), there are other reports of high frequencies of beneficial mutations (Silander et al 2007;Perfeito et al 2007, Perfeito et al 2014Hall et al 2008;Zhang et al 2011;Schaack et al 2013;Böndel et al 2019). Similar results of a high frequency of beneficial mutations were previously found for mutation accumulation lines from the A. thaliana Columbia accession (Shaw et al 2002;Rutter et al 2010;Roles et al 2016;Rutter et al 2018) and independently derived MA lines from the same founder (MacKenzie et al 2005).…”

“…2013; Böndel et al. 2019). Similar results of a high frequency of beneficial mutations were previously found for mutation accumulation lines from the A. thaliana Columbia accession (Shaw et al.…”