The ecology and genetics of fitness in Chlamydomonas. XIII. Fitness of long-term sexual and asexual populations in benign environments

We measured the mean fitness of populations of Chlamydomonas reinhardtii maintained in the laboratory as obligately sexual or asexual populations for about 100 sexual cycles and about 1000 asexual generations. Sexuality (random gamete fusion followed by meiosis) is expected to reduce mutational load and increase mean fitness by combining deleterious mutations from different lines of descent. We found no evidence for this process of mutation clearance: the mean fitness of sexual populations did not exceed that of asexual populations, whether measured through competition or in pure culture. We found instead that sexual progeny suffer an immediate loss in fitness, and that sexual lines maintain genetic variance for fitness. We suggest that sexual populations at equilibrium with selection in a benign environment may be mixtures of several or many epistatic genotypes with nearly equal fitness. Recombination between these genotypes reduces mean fitness and creates genetic variance for fitness. This may provide fuel for continued selection should the environment change.     

Estimation of the rate and effect of new beneficial mutations in asexual populations

The rate and effect of available beneficial mutations are key parameters in determining how a population adapts to a new environment. However, these parameters are poorly known, in large part because of the difficulty of designing and interpreting experiments to examine the rare and intrinsically stochastic process of mutation occurrence. We present a new approach to estimate the rate and selective advantage of beneficial mutations that underlie the adaptation of asexual populations. We base our approach on the analysis of experiments that track the effect of newly arising beneficial mutations on the dynamics of a neutral marker in evolving bacterial populations and develop efficient estimators of mutation rate and selective advantage. Using extensive simulations, we evaluate the accuracy of our estimators and conclude that they are quite robust to the use of relatively low experimental replication. To validate the predictions of our model, we compare theoretical and experimentally determined estimates of the selective advantage of the first beneficial mutation to fix in a series of ten replicate populations. We find that our theoretical predictions are not significantly different from experimentally determined selection coefficients. Application of our method to suitably designed experiments will allow estimation of how population evolvability depends on demographic and initial fitness parameters.     

Epistasis can accelerate adaptive diversification in haploid asexual populations

A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification.     

Population subdivision and adaptation in asexual populations of Saccharomyces cerevisiae

Population subdivision limits competition between individuals, which can have a profound effect on adaptation. Subdivided populations maintain more genetic diversity at any given time compared to well-mixed populations, and thus "explore" larger parts of the genotype space. At the same time, beneficial mutations take longer to spread in such populations, and thus subdivided populations do not "exploit" discovered mutations as efficiently as well-mixed populations. Whether subdivision inhibits or promotes adaptation in a given environment depends on the relative importance of exploration versus exploitation, which in turn depends on the structure of epistasis among beneficial mutations. Here we investigate the relative importance of exploration versus exploitation for adaptation by evolving 976 independent asexual populations of budding yeast with several degrees of geographic subdivision. We find that subdivision systematically inhibits adaptation: even the luckiest demes in subdivided populations on average fail to discover genotypes that are fitter than those discovered by well-mixed populations. Thus, exploitation of discovered mutations is more important for adaptation in our system than a thorough exploration of the mutational neighborhood, and increasing subdivision slows adaptation.     

The evolution of mutation rate in finite asexual populations

In this article, we model analytically the evolution of mutation rate in asexual organisms. Three selective forces are present. First, everything else being equal, individuals with higher mutation rate have a larger fitness, thanks to the energy and time saved by not replicating DNA accurately. Second, as a flip side, the genome of these individuals is replicated with errors that may negatively affect fitness. Third, and conversely, replication errors have a potential benefit if beneficial mutations are to be generated. Our model describes the fate of modifiers of mutation rate under the three forces and allows us to predict the long-term evolutionary trajectory of mutation rate. We obtain three major results. First, in asexuals, the needs for both adaptation and genome preservation are not evolutionary forces that can stabilize mutation rate at an intermediate optimum. When adaptation has a significant role, it primarily destabilizes mutation rate and yields the emergence of strong-effect mutators. Second, in contrast to what is usually believed, the appearance of modifiers with large mutation rate is more likely when the fitness cost of each deleterious mutation is weak, because the cost of replication errors is then paid after a delay. Third, in small populations, and even if adaptations are needed, mutation rate is always blocked at the minimum attainable level, because the rate of adaptation is too slow to play a significant role. Only populations whose size is above a critical mass see their mutation rate affected by the need for adaptation.     

A fitness based analysis of Daisyworld

The Gaia hypothesis [Lovelock, J., Margulis, L., 1974. Atmospheric homeostasis: the Gaia hypothesis. Tellus 26, 1], that the earth functions as a self-regulating system, has never sat particularly comfortably with ideas in mainstream biology [Anon, 2002. In pursuit of arrogant simplicities. Nature 416, 247]. A lack of any clear role for evolution in the model has led to claims of teleology-that self-regulation emerges because it is pre-ordained to do so [Doolittle, W.F., 1981. Is nature really motherly? CoEvol. Q. 58-63; Dawkins, R., 1979. The Extended Phenotype. Oxford University Press, Oxford]. The Daisyworld parable [Watson, A.J., Lovelock, J.E., 1983. Biological homeostasis of the global environment--the parable of Daisyworld. Tellus B 35, 284], a simple mathematical illustration of Gaia, went some way to addressing these critiques but, despite recent success in incorporating natural selection [Stocker, S.,1995. Regarding mutations in Daisyworld models. J. Theor. Biol. 175, 495; Lenton, T.M., 1998. Gaia and natural selection. Nature 394, 439; Lenton, T.M., Lovelock, J.E., 2001. Daisyworld revisited: quantifying biological effects on planetary self-regulation. Tellus B 53, 288; Wood, A.J., Ackland, G.J., Lenton, T.M., 2006. Mutation of albedo and growth response leads to oscillations in a spatial Daisyworld. J. Theor. Biol. 242, 188], it remains a widely held view that the ideas are inconsistent with biological principles. We show that standard methodology from quantitative genetics can be used to predict the stationary states and dynamic behaviour of Daisyworlds. The system regulates its temperature due to the low-level evolutionary dynamics of competition between the thermally coupled daisies, no higher level principle is invoked. A reconciliation of Gaia with evolutionary theory may allow further development of evolutionary arguments for the existence of global self-regulatory systems.     

Genetic polymorphisms in three Alpine populations (Visp valleys,Switerland)

Phenotype distributions and allele frequencies of 13 blood proteins are presented for the populations of the three Visp valleys, situated in the Swiss Alps. Blood samples of a total of 883 individuals were electrophoretically analysed. The three populations were statistically compared with each other, and with an additional sample from the literature thought to be representative of the entire Swiss population. Statistical differences are revealed and genetic distances are presented. These results are interpreted in connection with differences between the Visp valleys in topological situation.     

Limits to adaptation in asexual populations

In asexual populations, the rate of adaptation is basically limited by the frequency and properties of spontaneous beneficial mutations. Hence, knowledge of these mutational properties and how they are affected by particular evolutionary conditions is a precondition for understanding the process of adaptation. Here, we address how the rate of adaptation of asexual populations is limited by its population size and mutation rate, as well as by two factors affecting the fraction of mutations that confer a benefit, i.e. the initial adaptedness of the population and the variability of the environment. These factors both influence which mutations are likely to occur, as well as the probability that they will ultimately contribute to adaptation. We attempt to separate the consequences of these basic population features in terms of their effect on the rate of adaptation by using results from evolution experiments with microorganisms.     

The pace of evolution across fitness valleys

How fast does a population evolve from one fitness peak to another? We study the dynamics of evolving, asexually reproducing populations in which a certain number of mutations jointly confer a fitness advantage. We consider the time until a population has evolved from one fitness peak to another one with a higher fitness. The order of mutations can either be fixed or random. If the order of mutations is fixed, then the population follows a metaphorical ridge, a single path. If the order of mutations is arbitrary, then there are many ways to evolve to the higher fitness state. We address the time required for fixation in such scenarios and study how it is affected by the order of mutations, the population size, the fitness values and the mutation rate.     

The effect of population bottlenecks on mutation rate evolution in asexual populations

In the absence of recombination, a mutator allele can spread through a population by hitchhiking with beneficial mutations that appear in its genetic background. Theoretical studies over the past decade have shown that the survival and fixation probability of beneficial mutations can be severely reduced by population size bottlenecks. Here, we use computational modelling and evolution experiments with the yeast S. cerevisiae to examine whether population bottlenecks can affect mutator dynamics in adapting asexual populations. In simulation, we show that population bottlenecks can inhibit mutator hitchhiking with beneficial mutations and are most effective at lower beneficial mutation supply rates. We then subjected experimental populations of yeast propagated at the same effective population size to three different bottleneck regimes and observed that the speed of mutator hitchhiking was significantly slower at smaller bottlenecks, consistent with our theoretical expectations. Our results, thus, suggest that bottlenecks can be an important factor in mutation rate evolution and can in certain circumstances act to stabilize or, at least, delay the progressive elevation of mutation rates in asexual populations. Additionally, our findings provide the first experimental support for the theoretically postulated effect of population bottlenecks on beneficial mutations and demonstrate the usefulness of studying mutator frequency dynamics for understanding the underlying dynamics of fitness‐affecting mutations.     

Hierarchical distribution of ascending slopes, nearly neutral networks, highlands, and local optima at the dth order in an NK fitness landscape

We obtained several structural features of an NK fitness landscape by analytical approach. Particularly, we focused on spatial distributions of “ascending slopes”, “highlands”, “nearly neutral networks”, and “local optima” along the fitness coordinate W, from the viewpoint of adaptive walks with step-width d , where d is the number of mutated sites (Hamming distance) after a generation. The parameter k governs the degree of the ruggedness on the NK landscape, and we handled cases where k is moderate against the sequence length. From the foot up to the middle region on the landscape, many ascending slopes exist (high evolvability) and these slopes extend up near the “highland”, which is mathematically defined as the specific region where the expectation of the fitness increment becomes zero. Denoting the standard deviation of the fitness change at by SD^*, we considered the existence of “nearly neutral networks”, which percolate in the fitness band between W-SD^* and W+SD^*. Our results suggest that the highland corresponds to a phase-transition threshold of the formation of the nearly neutral networks. Near or over the highland, “local optima at the dth order” appear drastically (low evolvability), where d means the radius of their basins. The value of increases with d increasing. Then, as the fitness (=altitude) becomes higher, the basin size of the local optima increases. This leads to a conclusion that it is very hard or impossible for walkers with step-width d to reach near the global peak when d is a realistic large value: d=1-6, and suggests that the region over the middle in real landscapes may be considerably smooth with small k-values to maintain high evolvability.     

Correlations between sex rate estimates and fitness across predominantly parthenogenetic flatworm populations

One explanation for the success of sexual reproduction is that sex increases the efficacy of natural selection. Recombination and segregation lead to fitness variance among offspring which then offers a wider target for natural selection. Consequently, adaptation to changing environments is accelerated and population mean fitness will increase. We investigated whether low levels of sex are associated with increased fitness variance and mean in parthenogenetic biotypes of the planarian flatworm Schmidtea polychroa. Parthenogenetic S. polychroa are triploid and reproduce clonally with occasional sexual reproduction. By-products and measures of occasional sex are the local presence of tetraploids and elevated levels of genotypic diversity. We correlated the proportion of tetraploids and genotypic diversity with fitness attributes of six genetically differentiated locations within one meta-population. Results indicate strong, positive correlations with variance and with mean offspring number produced during a 5-week period. The ecological and evolutionary implications for the maintenance of parthenogenetic S. polychroa are discussed.     

Effective sizes of livestock populations to prevent a decline in fitness

In livestock populations, fitness may decrease due to inbreeding depression or as a negatively correlated response to artificial selection. On the other hand, fitness may increase due to natural selection. In the absence of a correlated response due to artificial selection, the critical population size at which the increase due to natural selection and the decrease due to inbreeding depression balance each other is approximately D/2_wa ², where D=the inbreeding depression of fitness with complete inbreeding, and _wa ²=the additive genetic variance of fitness. This simple expression agrees well with results from transmission probability matrix methods. If fitness declines as a correlated negative response to artificial selection, then a large increase in the critical effective population size is needed. However, if the negative response is larger than the response to natural selection, a reduction in fitness cannot be prevented. From these results it is concluded that a negative correlation between artificial and natural selection should be avoided. Effective sizes to prevent a decline in fitness are usually larger than those which maximize genetic gain of overall efficiency, i.e., the former is a more stringent restriction on effective size. In the examples presented, effective sizes ranged from 31 to 250 animals per generation.     

Epistasis from functional dependence of fitness on underlying traits

Epistasis between mutations in two genes is thought to reflect an interdependence of their functions. While sometimes epistasis is predictable using mechanistic models, its roots seem, in general, hidden in the complex architecture of biological networks. Here, we ask how epistasis can be quantified based on the mathematical dependence of a system-level trait (e.g. fitness) on lower-level traits (e.g. molecular or cellular properties). We first focus on a model in which fitness is the difference between a benefit and a cost trait, both pleiotropically affected by mutations. We show that despite its simplicity, this model can be used to analytically predict certain properties of the ensuing distribution of epistasis, such as a global negative bias, resulting in antagonism between beneficial mutations, and synergism between deleterious ones. We next extend these ideas to derive a general expression for epistasis given an arbitrary functional dependence of fitness on other traits. This expression demonstrates how epistasis relative to fitness can emerge despite the absence of epistasis relative to lower level traits, leading to a formalization of the concept of independence between biological processes. Our results suggest that epistasis may be largely shaped by the pervasiveness of pleiotropic effects and modular organization in biological networks.     

Habitat heterogeneity favors asexual reproduction in natural populations of grassthrips

Explaining the overwhelming success of sex among eukaryotes is difficult given the obvious costs of sex relative to asexuality. Different studies have shown that sex can provide benefits in spatially heterogeneous environments under specific conditions, but whether spatial heterogeneity commonly contributes to the maintenance of sex in natural populations remains unknown. We experimentally manipulated habitat heterogeneity for sexual and asexual thrips lineages in natural populations and under seminatural mesocosm conditions by varying the number of hostplants available to these herbivorous insects. Asexual lineages rapidly replaced the sexual ones, independently of the level of habitat heterogeneity in mesocosms. In natural populations, the success of sexual thrips decreased with increasing habitat heterogeneity, with sexual thrips apparently only persisting in certain types of hostplant communities. Our results illustrate how genetic diversity‐based mechanisms can favor asexuality instead of sex when sexual lineages co‐occur with genetically variable asexual lineages.     

Epistasis buffers the fitness effects of rifampicin- resistance mutations in Pseudomonas aeruginosa

Epistatic interactions between resistance mutations in antibiotic-free environments potentially play a crucial role in the spread of resistance in pathogen populations by determining the fitness cost associated with resistance. We used an experimental evolution approach to test for epistatic interactions between 14 different pairs of rifampicin mutations in the pathogenic bacterium Pseudomonas aeruginosa in 42 different rifampicin-free environments. First, we show that epistasis between rifampicin-resistance mutations tends to be antagonistic: the fitness effect of having two mutations is generally smaller than that predicted from the effects of individual mutations on the wild-type. Second, we show that sign epistasis between resistance mutations is both common and strong; most notably, pairs of deleterious resistance mutations often partially or completely compensate for each others' costs, revealing a novel mechanism for compensatory adaptation. These results suggest that antagonistic epistasis between intragenic resistance mutations may be a key determinant of the cost of antibiotic resistance and compensatory adaptation in pathogen populations.