Frank H. Shaw

A COMPREHENSIVE MODEL OF MUTATIONS AFFECTING FITNESS AND INFERENCES FOR ARABIDOPSIS THALIANA

Abstract As the ultimate source of genetic variation, spontaneous mutation is essential to evolutionary change. Theoretical studies over several decades have revealed the dependence of evolutionary consequences of mutation on specific mutational properties, including genomic mutation rates, U, and the effects of newly arising mutations on individual fitness, s. The recent resurgence of empirical effort to infer these properties for diverse organisms has not achieved consensus. Estimates, which have been obtained by methods that assume mutations are unidirectional in their effects on fitness, are imprecise. Both because a general approach must allow for occurrence of fitness‐enhancing mutations, even if these are rare, and because recent evidence demands it, we present a new method for inferring mutational parameters. For the distribution of mutational effects, we retain Keightleys assumption of the gamma distribution, to take advantage of the flexibility of its shape. Because the conventional gamma is one sided, restricting it to unidirectional effects, we include an additional parameter, ρ, as an amount it is displaced from zero. Estimation is accomplished by Markov chain Monte Carlo maximum likelihood. Through a limited set of simulations, we verify the accuracy of this approach. We apply it to analyze data on two reproductive fitness components from a 17‐generation mutation‐accumulation study of a Columbia accession of Arabidopsis thaliana in which 40 lines sampled in three generations were assayed simultaneously. For these traits, U∼0.1–0.2, with distributions of mutational effects broadly spanning zero, such that roughly half the mutations reduce reproductive fitness. One evolutionary consequence of these results is lower extinction risks of small populations of A thaliana than expected from the process of mutational meltdown. A comprehensive view of the evolutionary consequences of mutation will depend on quantitatively accounting for fitness‐enhancing, as well as fitness‐reducing, mutations.

Joint Effects of Inbreeding and Local Adaptation on the Evolution of Genetic Load after Fragmentation

Disruption of gene flow among demes after landscape fragmentation can facilitate local adaptation but increase the effect of genetic drift and inbreeding. The joint effects of these conflicting forces on the mean fitness of individuals in a population are unknown. Through simulations, we explored the effect of increased isolation on the evolution of genetic load over the short and long term when fitness depends in part on local adaptation. We ignored genetic effects on demography. We modeled complex genomes, where a subset of the loci were under divergent selection in different localities. When a fraction of the loci were under heterogeneous selection, isolation increased mean fitness in larger demes made up of hundreds of individuals because of improved local adaptation. In smaller demes of tens of individuals, increased isolation improved local adaptation very little and reduced overall fitness. Short-term improvement of mean fitness after fragmentation may not be indicative of the long-term evolution of fitness. Whatever the deme size and potential for local adaptation, migration of one or two individuals per generation minimized the genetic load in general. The slow dynamics of mean fitness following fragmentation suggests that conservation measures should be implemented before the consequences of isolation on the genetic load become of concern.

Migration load in plants: role of pollen and seed dispersal in heterogeneous landscapes

Evolution of local adaptation depends critically on the level of gene flow, which, in plants, can be due to either pollen or seed dispersal. Using analytical predictions and individual‐centred simulations, we investigate the specific influence of seed and pollen dispersal on local adaptation in plant populations growing in patchy heterogeneous landscapes. We study the evolution of a polygenic trait subject to stabilizing selection within populations, but divergent selection between populations. Deviations from linkage equilibrium and Hardy–Weinberg equilibrium make different contributions to genotypic variance depending on the dispersal mode. Local genotypic variance, differentiation between populations and genetic load vary with the rate of gene flow but are similar for seed and pollen dispersal, unless the landscape is very heterogeneous. In this case, genetic load is higher in the case of pollen dispersal, which appears to be due to differences in the distribution of genotypic values before selection.

Rapid Independent Trait Evolution despite a Strong Pleiotropic Genetic Correlation

Genetic correlations are the most commonly studied of all potential constraints on adaptive evolution. We present a comprehensive test of constraints caused by genetic correlation, comparing empirical results to predictions from theory. The additive genetic correlation between the filament and the corolla tube in wild radish flowers is very high in magnitude, is estimated with good precision (), and is caused by pleiotropy. Thus, evolutionary changes in the relative lengths of these two traits should be constrained. Still, artificial selection produced rapid evolution of these traits in opposite directions, so that in one replicate relative to controls, the difference between them increased by six standard deviations in only nine generations. This would result in a 54% increase in relative fitness on the basis of a previous estimate of natural selection in this population, and it would produce the phenotypes found in the most extreme species in the family Brassicaceae in less than 100 generations. These responses were within theoretical expectations and were much slower than if the genetic correlation was zero; thus, there was evidence for constraint. These results, coupled with comparable results from other species, show that evolution can be rapid despite the constraints caused by genetic correlations.

Adaptive Differentiation of Quantitative Traits in the Globally Distributed Weed, Wild Radish (Raphanus raphanistrum)

Weedy species with wide geographical distributions may face strong selection to adapt to new environments, which can lead to adaptive genetic differentiation among populations. However, genetic drift, particularly due to founder effects, will also commonly result in differentiation in colonizing species. To test whether selection has contributed to trait divergence, we compared differentiation at eight microsatellite loci (measured as FST) to differentiation of quantitative floral and phenological traits (measured as QST) of wild radish (Raphanus raphanistrum) across populations from three continents. We sampled eight populations: seven naturalized populations and one from its native range. By comparing estimates of QST and FST, we found that petal size was the only floral trait that may have diverged more than expected due to drift alone, but inflorescence height, flowering time, and rosette formation have greatly diverged between the native and nonnative populations. Our results suggest the loss of a rosette and the evolution of early flowering time may have been the key adaptations enabling wild radish to become a major agricultural weed. Floral adaptation to different pollinators does not seem to have been as necessary for the success of wild radish in new environments.

Fitness of Arabidopsis thaliana mutation accumulation lines whose spontaneous mutations are known

Despite the fundamental importance of mutation to the evolutionary process, we have little knowledge of the direct consequences of specific spontaneous mutations to the fitness of the organism. Combining results of whole‐genome sequencing with repeated field assays of survival and reproduction, we quantify the combined effects on fitness of spontaneous mutations identified in Arabidopsis thaliana. We demonstrate that the effects are beneficial, deleterious, or neutral depending on the environmental context. Some lines, bearing mutations disrupting known loci, differ strongly in fitness from the founder or premutation genotype. Those effects vary across environments, for example, a line with a major deletion spanning a transcription factor gene expressed lower fitness than the founder under most conditions but exceeded the founders fitness in one environment. The large contribution of genotype by environment interaction (G × E) to mutation effects on fitness implies spatial and/or temporal variation in selection on new mutations and could contribute to the maintenance of standing genetic variation.

SPONTANEOUS MUTATION PARAMETERS FOR ARABIDOPSIS THALIANA MEASURED IN THE WILD

Mutations are the ultimate source of genetic diversity and their contributions to evolutionary process depend critically on their rate and their effects on traits, notably fitness. Mutation rate and mutation effect can be measured simultaneously through the use of mutation accumulation lines, and previous mutation accumulation studies measuring these parameters have been performed in laboratory conditions. However, estimation of mutation parameters for fitness in wild populations requires assays in environments where mutations are exposed to natural selection and natural environmental variation. Here we quantify mutation parameters in both the wild and greenhouse environments using 100 25th generation Arabidopsis thaliana mutation accumulation lines. We found significantly greater mutational variance and a higher mutation rate for fitness under field conditions relative to greenhouse conditions. However, our field estimates were low when scaled to natural environmental variation. Many of the mutation accumulation lines have increased fitness, counter to the expectation that nearly all mutations decrease fitness. A high mutation rate and a low mutational contribution to phenotypic variation may explain observed levels of natural genetic variation. Our findings indicate that mutation parameters are not fixed, but are variables whose values may reflect the specific environment in which mutations are tested.

POPULATION STRUCTURE OF MORPHOLOGICAL TRAITS IN CLARKIA DUDLEYANA. II. CONSTANCY OF WITHIN-POPULATION GENETIC VARIANCE

Recent quantitative genetic studies have attempted to infer long‐term selection responsible for differences in observed phenotypes. These analyses are greatly simplified by the assumption that the within‐population genetic variance remains constant through time and over space, or for the multivariate case, that the matrix of additive genetic variances and covariances (G matrix) is constant. We examined differences in G matrices and the association of these differences with differences in multivariate means (Mahalanobis D2) among 11 populations of the California endemic annual plant, Clarkia dudleyana. Based on nine continuous morphological traits, the relationship between Mahalanobis D2 and a distance measure summarizing differences in G matrices reflected no concomitant change in (co)variances with changes in means. Based on both broad‐ and narrow‐sense analyses, we found little evidence that G matrices differed between populations. These results suggest that both the additive and nonadditive (co)variances for traits have remained relatively constant despite changes in means.

WHAT FRACTION OF MUTATIONS REDUCES FITNESS? A REPLY TO KEIGHTLEY AND LYNCH

Reiterating arguments supporting the view that the ‘‘vast majority of mutations are deleterious,’’ Keightley and Lynch (2003) take issue with several aspects of the analysis and interpretation of a recent mutation-accumulation (M-A) experiment with Arabidopsis thaliana (Shaw et al. 2002). In hopes of eliminating misunderstanding, we here address their criticisms of this work. We begin, however, by considering prior evidence about two aspects of the distribution of mutational effects: the average effect on fitness of new mutations and the fraction of mutations that reduce fitness. Whereas the evolutionary implications of both aspects of distribution of mutational effects are profound, we note that evidence about the latter aspect is far weaker than that concerning the former. Direct evidence concerning directional tendency of effects of spontaneous mutations on fitness comes primarily from M-A studies, in which lines bearing mutations accumulated over numerous generations in the (near) absence of selection are grown contemporaneously with a control that is genetically similar to the founder from which the M-A lines were originally established. In such studies, the mean of fitness (in practice, a component of fitness), taken over all M-A lines, compared to the mean for the control provides evidence of directional tendency of the aggregate effects of new mutations, that is, the average of their effects. The best known M-A studies, those of Mukai (1964; Mukai et al. 1972) with Drosophila melanogaster, showed considerable reduction in fitness of late—generation M-A lines. Reexamination of these studies has called this evidence into question, in particular the validity of the control (Keightley 1996; Garcia-Dorado 1997; but see also Fry 2001). Accordingly, several more recent studies have focused on organisms for which it is possible to retain individuals in a quasi-inert state during the period of M-A, and later revive them for assays of fitness in experiments together with the advanced generation M-A lines. In studies of this kind, conclusive evidence of an overall tendency of mutations to reduce fitness, by the criterion that the mean of a fitness component averaged over M-A lines (mm-a) is significantly less than the control mean (m0) (i.e., mm-a , m0), has been obtained for fitness traits of several model organisms. These include Escherichia coli (population growth rate, Kibota and Lynch 1996), the nematode, Caenorhabditis elegans (productivity, survival to maturity, and generation rate, Vassilieva et al. 2000), Arabidopsis thaliana (number of seeds per fruit, Schultz et al. 1999), DNA repair-

Is Inbreeding Depression Lower in Maladapted Populations? A Quantitative Genetics Model

Despite abundant empirical evidence that inbreeding depression varies with both the environment and the genotypic context, theoretical predictions about such effects are still rare. Using a quantitative genetics model, we predict amounts of inbreeding depression for fitness emerging from Gaussian stabilizing selection on some phenotypic trait, on which, for simplicity, genetic effects are strictly additive. Given the strength of stabilizing selection, inbreeding depression then varies simply with the genetic variance for the trait under selection and the distance between the mean breeding value and the optimal phenotype. This allows us to relate the expected inbreeding depression to the degree of maladaptation of the population to its environment. We confront analytical predictions with simulations, in well-adapted populations at equilibrium, as well as in maladapted populations undergoing either a transient environmental shift, or gene swamping in heterogeneous habitats. We predict minimal inbreeding depression in situations of extreme maladaptation. Our model provides a new basis for interpreting experiments that measure inbreeding depression for the same set of genotypes in different environments, by demonstrating that the history of adaptation, in addition to environmental harshness per se, may account for differences in inbreeding depression.