[
International Worm Meeting,
2015]
The rate and spectrum of spontaneous mutation vary at many hierarchical levels, from within individual genomes to among Domains of life. An interesting possibility, for which there is some evidence, is that the mutation rate varies inversely with fitness, such that individuals with low fitness have elevated mutation rates. To systematically investigate that possibility, we allowed mutations to accumulate for approximately 150 generations under relaxed selection in 10 sets of "second-order mutation accumulation" (MA) lines of the nematode C. elegans. Each set of second-order lines was derived from a different "first-order MA line" from a set of MA lines that had accumulated mutations for 250 generations. Of the 10 sets of second-order MA lines, five were derived from a first-order line with high fitness and five were derived from a first-order line with low fitness. Five replicate second-order MA lines from each set of first-order lines and the ten first-order progenitors were sequenced at ~25X genome-wide coverage using standard Illumina technology. The average base-substitution mutation rate does not differ between the High Fitness and Low Fitness treatment, but there is significantly greater variation in mutation rate among first-order lines within the Low Fitness treatment. Those results broadly recapitulate the results for relative fitness itself. In contrast, the High Fitness treatment had a higher rate of small indels. There is an overall deletion bias (3D:2I) which does not differ between the High and Low fitness treatments. Pooled over treatments, there is significant among-line variance in mutation rate, from which we conclude that the genomic mutation rate presents a substantial mutational target. Averaged over all lines, the transition/transversion ratio is 0.72, very close to the previously observed value for and considerably less than the standing Ts/Tv ratio in C. elegans. We observed that single-nucleotide mutations are twice as likely to be found in introns as in exons, and small indels are five-fold more likely to be found in introns as in exons. Those results indicate that a substantial fraction of mutations are removed by purifying selection even at very small effective population size. .