The distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii inferred using frequency changes under experimental evolution

The distribution of fitness effects (DFE) for new mutations is fundamental for many aspects of population and quantitative genetics. In this study, we have inferred the DFE in the single-celled alga Chlamydomonas reinhardtii by estimating changes in the frequencies of 254 spontaneous mutations under experimental evolution and equating the frequency changes of linked mutations with their selection coefficients. We generated seven populations of recombinant haplotypes by crossing seven independently derived mutation accumulation lines carrying an average of 36 mutations in the haploid state to a mutation-free strain of the same genotype. We then allowed the populations to evolve under natural selection in the laboratory by serial transfer in liquid culture. We observed substantial and repeatable changes in the frequencies of many groups of linked mutations, and, surprisingly, as many mutations were observed to increase as decrease in frequency. Mutation frequencies were highly repeatable among replicates, suggesting that selection was the cause of the observed allele frequency changes. We developed a Bayesian Monte Carlo Markov Chain method to infer the DFE. This computes the likelihood of the observed distribution of changes of frequency, and obtains the posterior distribution of the selective effects of individual mutations, while assuming a two-sided gamma distribution of effects. We infer that the DFE is a highly leptokurtic distribution, and that approximately equal proportions of mutations have positive and negative effects on fitness. This result is consistent with what we have observed in previous work on a different C. reinhardtii strain, and suggests that a high fraction of new spontaneously arisen mutations are advantageous in a simple laboratory environment. Author summaryMutations are the ultimate source of genetic variation, form the raw material for evolution under natural selection, and generate a genetic load of harmful variants that are selectively removed from populations. Here, we have estimated the relative numbers of mutations with different sizes of effects on fitness in a laboratory strain of the model unicellular green alga Chlamydomonas reinhardtii. We estimated the fitness effects of mutations by measuring their frequency changes under experimental evolution in replicated populations where mutant allele frequencies started at 0.5 and where different genotypes might express different fitnesses. We developed a method to infer fitness effects based on changes of allele frequency; for example mutations that consistently decreased in frequency would be inferred to have a negative effect. While the majority of mutational effects were close to zero, we found that a high proportion of mutations increased in frequency under experimental evolution, implying that they had positive fitness effects in the laboratory environment. This is unexpected, because many mutations in natural populations have deleterious effects, and advantageous mutations appear to be rare.