Fitness decline under osmotic stress inCaenorhabditis eleganspopulations subjected to spontaneous mutation accumulation at varying population sizes

Abstract

The consequences of mutations for population fitness depends on their individual selection coefficients and the effective population size. An earlier study of Caenorhabditis elegans spontaneous mutation accumulation lines evolved for 409 generations at three population sizes found that N = 1 populations declined significantly in fitness whereas the fitness of larger populations (N = 5, 50) was indistinguishable from the ancestral control under benign conditions. To test if larger MA populations harbor a load of cryptic deleterious mutations that are obscured under benign laboratory conditions, we measured fitness under osmotic stress via exposure to hypersaline conditions. The fitness of N = 1 lines exhibited a further decline under osmotic stress compared to benign conditions. However, the fitness of larger populations remained indistinguishable from that of the ancestral control. The average effects of deleterious mutations in N = 1 lines were estimated to be 22% for productivity and 14% for survivorship, exceeding values previously detected under benign conditions. Our results suggest that fitness decline is due to large effect mutations that are rapidly removed via selection even in small populations, with implications for conservation practices. Genetic stochasticity may not be as potent and immediate a threat to the persistence of small populations as other demographic and environmental stochastic factors.

Mutational Landscape of Spontaneous Base Substitutions and Small Indels in Experimental Caenorhabditis elegans Populations of Differing Size

“…We sequenced the genomes of 86 C. elegans MA lines and their N2 ancestor from a long-term MA experiment with differing population sizes (Katju et al 2015(Katju et al , 2018Konrad et al 2017Konrad et al , 2018. The MA phase of the experiment lasted for 409 generations and comprised three population-size treatments, wherein a new worm generation was established with N = 1, 10, or 100 hermaphrodite worms (Supplemental Material, Figure S1A).…”

“…A new generation was established every 4 days. The N = 1, 10, and 100 population-size treatments corresponded to effective population sizes (N e ) of 1, 5, and 50, respectively (Katju et al 2015(Katju et al , 2018. The worms were cultured using standard techniques with maintenance at 20°on NGM agar in (i) 60 3 15 mm Petri dishes seeded with 250 ml suspension of Escherichia coli strain OP50 in YT media (N = 1 and N = 10 lines) or (ii) 90 3 15 mm Petri dishes seeded with 750 ml suspension of E. coli strain OP50 in YT media (N = 100 lines).…”

“…Of the 199 substitutions detected in the exons, 195 were verified by RNA-Seq data. The four variants that could not be validated by RNA-Seq were associated with line 1T, which went extinct at MA generation 309 (Katju et al 2015(Katju et al , 2018. RNA for line 1T was extracted from an earlier stock cryopreserved at MA generation 305.…”

“…This experimental design permits a simultaneous investigation of the effects of spontaneous mutation and selection on genetic variation, as well as indirect inferences of the fitness consequences of different classes of mutations. Here, we employ the same set of spontaneous C. elegans MA lines comprising three population-size treatments (Katju et al 2015(Katju et al , 2018Konrad et al 2017Konrad et al , 2018, and leverage this experimental framework with high-throughput sequencing to identify de novo nuclear base substitutions and small insertion/deletions (indels) on a genome-wide scale since the divergence of the MA lines from their common ancestor. With the completion of this study, we are able to: (i) offer a comprehensive view of the spontaneous mutation process in C. elegans, across both the organellar and nuclear genomes, and all major classes of mutations (base substitutions, small indels, and copynumber variations); (ii) compare our spontaneous mutation rates for nuclear SNPs to previously generated rates that employed older sequencing technologies; (iii) provide one of the first direct, genome-wide estimates of the spontaneous small indel rate for a nematode; and (iv) investigate selective constraints that may impinge on nuclear base substitutions and small indels.…”

Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans

“…We employed a spontaneous MA experiment design comprising three population size treatments in Caenorhabditis elegans (12)(13)(14). MA lines, all descended from a single N2 hermaphrodite ancestor, were bottlenecked each generation at N = 1, 10, or 100 hermaphrodites (SI Appendix, Fig.…”