title: Mutation accumulation in populations of varying size: the distribution of mutational effects for fitness correlates in Caenorhabditis elegans.
abstract: The consequences of mutation for population-genetic and evolutionary processes depend on the rate and, especially, the frequency distribution of mutational effects on fitness. We sought to approximate the form of the distribution of mutational effects by conducting divergence experiments in which lines of a DNA repair-deficient strain of Caenorhabditis elegans, msh-2, were maintained at a range of population sizes. Assays of these lines conducted in parallel with the ancestral control suggest that the mutational variance is dominated by contributions from highly detrimental mutations. This was evidenced by the ability of all but the smallest population-size treatments to maintain relatively high levels of mean fitness even under the 100-fold increase in mutational pressure caused by knocking out the msh-2 gene. However, we show that the mean fitness decline experienced by larger populations is actually greater than expected on the basis of our estimates of mutational parameters, which could be consistent with the existence of a common class of mutations with small individual effects. Further, comparison of the total mutation rate estimated from direct sequencing of DNA to that detected from phenotypic analyses implies the existence of a large class of evolutionarily relevant mutations with no measurable effect on laboratory fitness.
authors.affiliation: Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, Oregon 97403, USA. estessu@science.oregonstate.edu
authors.forename: Suzanne
authors.initials: S
authors.lastname: Estes
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Phillips
authors.forename: Dee R
authors.initials: DR
authors.lastname: Denver
authors.forename: W Kelley
authors.initials: WK
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004260:DNA Repair; D017238:Genes, Helminth; D014644:Genetic Variation; D005828:Genetics, Population; D051719:MutS DNA Mismatch-Binding Protein; D009154:Mutation; D011156:Population Density; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D029742:Caenorhabditis elegans Proteins; C450145:msh-2 protein, C elegans; D051719:MutS DNA Mismatch-Binding Protein