Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans

Abstract

BackgroundThe accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci.Methodology/Principal FindingsWe tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase.ConclusionsCompensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction.

Experimental Evolution withCaenorhabditisNematodes

“…Although rapid fitness recovery from mutationally degraded backgrounds can be achieved by selfing alone (Estes et al 2004; Morran et al 2010), these results strongly suggest that outcrossing increases effective recombination and allows the generation of more adaptive genotypes than does selfing.…”

MainstreamingCaenorhabditis elegansin experimental evolution

“…Alternatively, initially isogenic experimental populations can be stocked with new mutations by chemical mutagenesis [40][41][42][43] or with genetics, such as from a knockout of a mismatch repair gene [44,45]. RNAi knockdown of DNA repair genes provides an inducible means of introducing new mutations with an endogenous mutational spectrum [46].…”

SAPling: a Scan-Add-Print barcoding database system to label and track asexual organisms

“…This method is also applicable to parthenogenetic organisms, such as Daphnia (Hebert and Ward, 1972;Lynch et al, 1989), aphids (Wilson et al, 2003;Kanbe andAkimoto, 2009), certain lizards (Cuellar, 1981;Cuellar, 1984;Badaeva et al, 2008) and selffertilizing hermaphrodites, such as Caenorhabditis elegans (Keightley and Caballero, 1997;Morran et al, 2010). The only difference here is that such organisms can produce clutches of multiple offspring.…”