Selection on a Subunit of the NURF Chromatin Remodeler Modifies Life History Traits in a Domesticated Strain of Caenorhabditis elegans

Abstract

Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual's resources to competing life functions. Although life-history traits evolve rapidly, little is known about the genetic and cellular mechanisms that control and couple these tradeoffs. Here, we find that two laboratory-adapted strains of C. elegans descended from a single common ancestor that lived in the 1950s have differences in a number of life-history traits, including reproductive timing, lifespan, dauer formation, growth rate, and offspring number. We identified a quantitative trait locus (QTL) of large effect that controls 24%-75% of the total trait variance in reproductive timing at various timepoints. Using CRISPR/Cas9-induced genome editing, we show this QTL is due in part to a 60 bp deletion in the 3' end of the nurf-1 gene, which is orthologous to the human gene encoding the BPTF component of the NURF chromatin remodeling complex. Besides reproduction, nurf-1 also regulates growth rate, lifespan, and dauer formation. The fitness consequences of this deletion are environment specific-it increases fitness in the growth conditions where it was fixed but decreases fitness in alternative laboratory growth conditions. We propose that chromatin remodeling, acting through nurf-1, is a pleiotropic regulator of life history trade-offs underlying the evolution of multiple traits across different species.

Fig 1. Laboratory adaptation of C. elegans strains has resulted in modified reproductive rate and timing.

a. History of the C. elegans strains N2 and LSJ2 following isolation from the wild (Bristol, England). LSJ2 was grown in liquid axenic culture whereas N2 was propagated on agar plates. b. Schematic of CX12311 genetic background containing ancestral alleles of npr-1 and glb-5 backcrossed from CB4856. CB4856 is a wild strain isolated from Hawaii. c. Schematic of egg-laying experiments performed in d and e. d. Averaged egg-laying rate of the CX12311, LSJ2, and daf-22 strains starting from the L4 stage. daf-22 encodes an enzyme necessary for synthesis of ascaroside pheromones. e. Total number of eggs laid per animal for the three strains from d. Error bars in d and e represent s.e.m.

Fig 2. QTL mapping of differences in LSJ2 and CX12311 reproductive rate and timing.

a. Schematic of egg-laying experiments performed on 94 recombinant inbred lines (RILs) generated between LSJ2 and CX12311. b. Histogram of the egg-laying rate measured from 94 RILs at five different time points. c. QTL mapping on data from B identified a major effect locus on the right arm of chromosome II at all five time points. Additional smaller effect QTL were identified for a subset of time points on chromosomes IV, V, and X. Stars identify QTL that reach genome-wide significance. d. Egg-laying rate of RILs partitioned by their genotype at the genetic variant with the peak LOD score (WBVar00601585) in the major effect QTL on the right arm of chromosome II. The effect of this variant was age dependent. Mean and s.e.m. plotted immediately to the right. Number in the upper right indicates percent of phenotypic variation explained by the QTL.

Fig 3. The major-effect QTL on II is partially explained by a 60 bp deletion in nurf-1.

a. QTL mapping at four time points plotted on the right arm of chromosome II. Bayesian significance interval is shown as a bar (S.I.). Genetic variants between LSJ2 and N2 plotted along the x-axis (color indicates their location; height of bar has no significance). The boundaries of an introgressed region created surrounding this QTL are shown below the x-axis (kyIR87). b. Egg-laying rate of N2, CX12311, NIL_nurf-1, ARL_nurf-1, and nurf-1(n4295). NIL_nurf-1 is an introgression of LSJ2 DNA near nurf-1 (kyIR87, see a) into CX12311. ARL_nurf-1 is the result of engineering the LSJ2 deletion in nurf-1 into the CX12311 background using CRISPR/Cas9. Two independent ARL_nurf-1 strains were constructed and data show the average of both strains. The nurf-1(n4295) strain was constructed in the N2 background. Black stars (top of triangle) indicate significant differences between N2 and nurf-1(n4295). Green stars (bottom left) indicate significant differences between CX12311 and NIL_nurf-1. Red stars (bottom right) indicate significant differences between CX12311 and ARL_nurf-1. Error bars represent S.E.M. c. Genomic region surrounding nurf-1 indicating the location of two canonical mutagenesis-derived alleles (n4293, n4295), N2-fixed SNP (WBVar00601361), and LSJ2-fixed 60 bp deletion (WBVar00601565), predicted mRNA and protein product, and predicted effect on protein sequence of the LSJ2 deletion. Isoforms that are predicted to be affected by the WBVar00601565 deletion are colored in light red.

Fig 4. nurf-1 regulates additional life-history traits.

a. Dauer formation of the N2, LSJ2, CX12311, ARL_nurf-1, and nurf-1(n4295), strains in response to crude pheromone or N2, LSJ2, and nurf-1(n4295) in response to synthesized pheromone components. y-axis indicates the percentage of animals that enter dauer in response to the pheromone concentrations listed on the x-axis averaged from at least fiver replicates. Stars indicate significant differences (p<0.05) from the N2 strain. b. Lifespan analysis of the N2, LSJ2, CX12311, ARL_nurf-1 and nurf-1(4295) animals. At least three independent replicates containing ~60 worms were used for this analysis. The LSJ2 and ARL_nurf-1 strain were both significantly different (p < 0.05) than CX12311. The nurf-1(4295) strain was not significantly different from the N2 strain. c. Micrograph comparing the size of N2 and nurf-1(n4295) animals. Embryos were isolated from each strain and allowed to hatch and grow on agar plates for 72 hours. d. Growth rate of N2, LSJ2, CX12311, ARL_nurf-1 and nurf-1(n4295) strains. y-axis shows the average area of each animal measured by videotracking normalized to the N2 strain. Three independent growth plates were analyzed each day and three replicates were performed on different days. Their size was measured 72–75 hours after isolation. Stars indicate significant differences (p<0.05).

Fig 5. The 60 bp deletion in nurf-1 is advantageous in liquid axenic media but disadvantageous on agar plates.

A diagram of the two competition conditions is shown above the graph. The ARL_nurf-1 strain (PTM88) was competed against CX12311. The fraction of ARL_nurf-1 animals in the population is shown on the y-axis. The equation for a linear regression fit is also shown on the graph. p value indicates significance of the temporal term by ANOVA. Error bars represent standard error.

Fig 6. Average length of a population of RILs partitioned by their genotype at nurf-1 (WBVar00601585) as measured by a COPAS BIOSORT in response to a variety of abiotic stressors.

Time of flight is correlated with average length of the animals. Water and DMSO are controls for solvents necessary to dissolve the various abiotics.