On the potential for extinction by Muller's ratchet in Caenorhabditis elegans

Abstract

Background: The self-fertile hermaphrodite worm C. elegans is an important model organism for biology, yet little is known about the origin and persistence of the self-fertilizing mode of reproduction in this lineage. Recent work has demonstrated an extraordinary degree of selfing combined with a high deleterious mutation rate in contemporary populations. These observations raise the question as to whether the mutation load might rise to such a degree as to eventually threaten the species with extinction. The potential for such a process to occur would inform our understanding of the time since the origin of self-fertilization in C. elegans history.

Results: To address this issue, here we quantify the rate of fitness decline expected to occur via Muller's ratchet for a purely selfing population, using both analytical approximations and globally distributed individual-based simulations from the evolution@home system to compute the rate of deleterious mutation accumulation. Using the best available estimates for parameters of how C. elegans evolves, we conclude that pure selfing can persist for only short evolutionary intervals, and is expected to lead to extinction within thousands of years for a plausible portion of parameter space. Credible lower-bound estimates of nuclear mutation rates do not extend the expected time to extinction much beyond a million years.

Conclusion: Thus we conclude that either the extreme self-fertilization implied by current patterns of genetic variation in C. elegans arose relatively recently or that low levels of outcrossing and other factors are key to the persistence of C. elegans into the present day. We also discuss results for the mitochondrial genome and the implications for C. briggsae, a close relative that made the transition to selfing independently of C. elegans.

Figure 1

Predicted extinction times of C. elegans based on mutations in the nuclear genome. (A) Analytical results only. (B) Analytical and simulation results combined. The solid, black horizontal line denotes the estimated divergence time of C. elegans relative to its closest known outcrossing relatives (18 Myr), including upper and lower limits (grey lines; the upper limit of about 100 Myr from some older studies is marked separately). Extinction time estimates below this line indicate that extinction by Muller's ratchet is expected to have occurred, under a scenario of pure self-fertilization since divergence from known outcrossing sister taxa. The bar along the bottom labeled N_es = 1 indicates the boundary for selective neutrality of mutational effects (for the range of N_e given in Table 1). Thick colored lines represent the analytic predictions of the extinction time for different effective deleterious genomic mutation rates (U_sdm) for N_e = 10 000, T_gen = 60 d, and R_max = 280 offspring/generation. Thin dashed lines demarcate bounds of uncertainty for U_sdm = 0.5, based on upper and lower limits of N_e, T_gen and R_max (Table 1); variability in extinction time is similar for other U_sdm. Large symbols denote valid extinction time estimates from independent simulation runs with two or more observed clicks of Muller's ratchet. Small symbols denote lower limits for extinction times from simulations without observed clicks, assuming that the ratchet would have clicked just after stopping the simulation. This plot contains 36 393 simulations with a total of 19.9 years of computing time. The nearly vertical right portion of the extinction time curves represents the "wall of background selection", indicating that mutations with larger effects are eliminated deterministically.

Figure 2

Predicted extinction times of C. elegans based on mutations in the mitochondrial genome. (A) Analytical results only. (B) Analytical and simulation results combined. See Figure 1 legend for details. Lower genomic deleterious mutation rates are chosen to reflect estimates for the mitochondrial genome (Table 1). Thin dashed lines indicate the uncertainty of the extinction time estimates for U_sdm = 0.001 using the corresponding upper and lower limits of N_e, T_gen and R_max. This plot contains 38 644 simulations with a total of 21.4 years of computing time.

Figure 3

Predicted reduction in divergence rates at sites that are under selection in nuclear genes of C. elegans due to Muller's ratchet. The black dashed lines indicate the effects of variability in N_e (1000 – 100 000). The histogram shows observed K_A/K_S values between C. elegans and C. briggsae, suggesting that observed divergence is roughly compatible with most selection coefficients having effects between about 0.1 and 0.0001. The inferred rate of fixation of deleterious mutations relative to the rate for neutral mutations is computed by dividing 1/U_sdm by the predicted effective click time (parameters as in Figure 1).

Figure 4

A point estimate for the distribution of deleterious mutational effects on fitness in Caenorhabditis. This point estimate was computed from comparing diversity data from C. elegans and C. remanei assuming a lognormal DDME. The fraction of effectively dominant lethal mutations estimated from this distribution is biologically plausible and indicated by the spike at s = 1. The vertical line denotes the border to effective neutrality for C. elegans at N_es = 0.5. See Methods for details.