We tested the ability of six quantitative genetic models to explain the evolution of phenotypic means using an extensive database compiled by Gingerich. Our approach differs from past efforts in that we use explicit models of evolutionary process, with parameters estimated from contemporary populations, to analyze a large sample of divergence data on many different timescales. We show that one quantitative genetic model yields a good fit to data on phenotypic divergence across timescales ranging from a few generations to 10 million generations. The key feature of this model is a fitness optimum that moves within fixed limits. Conversely, a model of neutral evolution, models with a stationary optimum that undergoes Brownian or white noise motion, a model with a moving optimum, and a peak shift model all fail to account for the data on most or all timescales. We discuss our results within the framework of Simpson's concept of adaptive landscapes and zones. Our analysis suggests that the underlying process causing phenotypic stasis is adaptation to an optimum that moves within an adaptive zone with stable boundaries. We discuss the implication of our results for comparative studies and phylogeny inference based on phenotypic characters.

The consequences of mutation for population-genetic and evolutionary processes depend on the rate and, especially, the frequency distribution of mutational effects on fitness. We sought to approximate the form of the distribution of mutational effects by conducting divergence experiments in which lines of a DNA repair-deficient strain of Caenorhabditis elegans, msh-2, were maintained at a range of population sizes. Assays of these lines conducted in parallel with the ancestral control suggest that the mutational variance is dominated by contributions from highly detrimental mutations. This was evidenced by the ability of all but the smallest population-size treatments to maintain relatively high levels of mean fitness even under the 100-fold increase in mutational pressure caused by knocking out the msh-2 gene. However, we show that the mean fitness decline experienced by larger populations is actually greater than expected on the basis of our estimates of mutational parameters, which could be consistent with the existence of a common class of mutations with small individual effects. Further, comparison of the total mutation rate estimated from direct sequencing of DNA to that detected from phenotypic analyses implies the existence of a large class of evolutionarily relevant mutations with no measurable effect on laboratory fitness.T HE rate at which mutations arise and the effects that cited and applied in many evolutionary and populationgenetic models. However, while some recent studies they exert on fitness are central to our understanding of a multitude of evolutionary processes. populaal. 2001;Shaw et al. 2002). The studies reporting low tions or those experiencing reduced natural selection mutation rates and large average effects include a long-(e.g., Barton and Turelli 1989; Charlesworth and term mutation-accumulation experiment conducted Charlesworth 1998; Kondrashov 1998; Lynch et al.with the "wild-type" Bristol N2 strain of the nematode 1999; Lynch and O'Hely 2001).Caenorhabditis elegans (Vassilieva and Lynch 1999; VasSubstantial effort has been devoted to determining silieva et al. 2000). Results from this study imply that the contributions of the mutation rate and the average the genomic deleterious mutation rate is perhaps as mutational effect to genetic variance, beginning with much as 20 times lower and the average mutational the landmark mutation-accumulation (MA) experieffect twice as high as that previously measured for D. ments conducted with Drosophila melanogaster by Mukai melanogaster. If this is a common pattern, deleterious (1964) and Mukai et al. (1972). A high polygenic mutamutation may prove insufficient to explain the diversity tion rate of one per individual per generation and a of evolutionary patterns in which it is currently implilow average mutational effect of Ͻ3% were suggested cated, as well as posing less of a threat to population by these studies, indicating that conditions necessary viability. for the accumulation of mutations via genetic drift in However, the ult...

The pattern of mutational covariance among traits plays a central, but largely untested, role in many theories in evolutionary genetics. Here we estimate the pattern of phenotypic, environmental, and mutational correlations for a set of life-history, behavioral, and morphological traits using 67 self-fertilizing lines of Caenorhabditis elegans, each having independently experienced an average of 370 generations of spontaneous mutation accumulation. Bivariate relationships of mutational effects indicate the existence of extensive pleiotropy. We find that mutations may tend to produce manifold effects on suites of functionally related traits; however, our data do not support the idea of completely parcelated pleiotropy, in which functional units are separately affected by mutations. Positive net phenotypic and mutational correlations are common for life-history traits, with environmental correlations being comparatively smaller and of the same sign for most pairs of traits. Observed mutational correlations are shown to be higher than those produced by the chance accumulation of nonpleiotropic mutations in the same lines.

Abstract. Deleterious mutation accumulation has been implicated in many biological phenomena and as a potentially significant threat to human health and the persistence of small populations. The vast majority of mutations with effects on fitness are known to be deleterious in a given environment, and their accumulation results in mean population fitness decline. However, whether populations are capable of recovering from negative effects of prolonged genetic bottlenecks via beneficial or compensatory mutation accumulation has not previously been tested. To address this question, long-term mutation-accumulation lines of the nematode Caenorhabditis elegans, previously propagated as single individuals each generation, were maintained in large population sizes under competitive conditions. Fitness assays of these lines and comparison to parallel mutation-accumulation lines and the ancestral control show that, while the process of fitness restoration was incomplete for some lines, full recovery of mean fitness was achieved in fewer than 80 generations. Several lines of evidence indicate that this fitness restoration was at least partially driven by compensatory mutation accumulation rather than a result of a generic form of laboratory adaptation. This surprising result has broad implications for the influence of the mutational process on many issues in evolutionary and conservation biology.

The hermaphroditic nematode Caenorhabditis elegans has been one of the primary model systems in biology since the 1970s, but only within the last two decades has this nematode also become a useful model for experimental evolution. Here, we outline the goals and major foci of experimental evolution with C. elegans and related species, such as C. briggsae and C. remanei, by discussing the principles of experimental design, and highlighting the strengths and limitations of Caenorhabditis as model systems. We then review three exemplars of Caenorhabditis experimental evolution studies, underlining representative evolution experiments that have addressed the: (1) maintenance of genetic variation; (2) role of natural selection during transitions from outcrossing to selfing, as well as the maintenance of mixed breeding modes during evolution; and (3) evolution of phenotypic plasticity and its role in adaptation to variable environments, including host–pathogen coevolution. We conclude by suggesting some future directions for which experimental evolution with Caenorhabditis would be particularly informative.