Nathaniel P. Sharp

MATING DENSITY AND THE STRENGTH OF SEXUAL SELECTION AGAINST DELETERIOUS ALLELES IN DROSOPHILA MELANOGASTER

Abstract Deleterious alleles constantly enter populations via mutation. Their presence reduces mean fitness and may threaten population persistence. It has been suggested that sexual selection may be an efficient way by which deleterious alleles are removed from populations but there is little direct experimental evidence. Because of its potential role in mutational meltdowns, there is particular interest in whether the strength of sexual selection changes with density. For each of eight visible markers in Drosophila melanogaster we have compared the strength of sexual selection at two densities. We find evidence of strong sexual selection against most but not all of these alleles. There is no evidence that sexual selection tends to be stronger (or weaker) at high density relative to low density. In addition, we also measure the effects of these mutations on two key parameters relevant to population productivity—juvenile viability and female fecundity. In most cases, sexual selection is as strong or stronger than these other forms of selection.

MALE-BIASED FITNESS EFFECTS OF SPONTANEOUS MUTATIONS IN DROSOPHILA MELANOGASTER

In populations with males and females, sexual selection may often represent a major component of overall selection. Sexual selection could act to eliminate deleterious alleles in concert with other forms of selection, thereby improving the fitness of sexual populations. Alternatively, the divergent reproductive strategies of the sexes could promote the maintenance of sexually antagonistic variation, causing sexual populations to be less fit. The net impact of sexual selection on fitness is not well understood, due in part to limited data on the sex‐specific effects of spontaneous mutations on total fitness. Using a set of mutation accumulation lines of Drosophila melanogaster, we found that mutations were deleterious in both sexes and had larger effects on fitness in males than in females. This pattern is expected to reduce the mutation load of sexual females and promote the maintenance of sexual reproduction.

Evidence for elevated mutation rates in low-quality genotypes

The deleterious mutation rate plays a key role in a number of important topics in biology, from mating system evolution to human health. Despite this broad significance, the nature and causes of variation in mutation rate are poorly understood, especially in multicellular organisms. We test whether genetic quality, the presence or absence of deleterious alleles, affects the mutation rate in Drosophila melanogaster by using a modified mutation accumulation approach. We find evidence that genotypes constructed to carry deleterious “treatment” alleles on one chromosome during mutation accumulation experience an elevated mutation rate on a different chromosome. Further, this elevation is correlated with the effect of the treatment alleles on phenotypic condition, measured as body mass. Treatment alleles that reduce mass by 10% cause a doubling in the rate of mutational decline. Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.

Selection, epistasis, and parent-of-origin effects on deleterious mutations across environments in Drosophila melanogaster.

Understanding the nature of selection against deleterious alleles is central to determining how populations are affected by the constant influx of new mutations. Important progress has been made in estimating basic attributes of the distribution of selection coefficients and gene interaction effects (epistasis). Although most aspects of selection are likely to be context dependent, little is known about the effect of stress on selection and epistasis at the level of individual genes, especially in multicellular organisms. Using Drosophila melanogaster, we measure how selection on 20 mutant alleles is affected by direct and indirect genetic factors across two environments. We find that environmental stress increases selection against individual mutations but reduces selection against combinations of mutations (i.e., epistasis becomes more positive). In addition, we find a high incidence of indirect genetic effects whereby the strength of selection against the alleles carried by offspring is dependent on the genotypes of their parents.

Sexual antagonism for resistance and tolerance to infection in Drosophila melanogaster

A critical task in evolutionary genetics is to explain the persistence of heritable variation in fitness-related traits such as immunity. Ecological factors can maintain genetic variation in immunity, but less is known about the role of other factors, such as antagonistic pleiotropy, on immunity. Sexually dimorphic immunity—with females often being more immune-competent—may maintain variation in immunity in dioecious populations. Most eco-immunological studies assess host resistance to parasites rather than the hosts ability to maintain fitness during infection (tolerance). Distinguishing between resistance and tolerance is important as they are thought to have markedly different evolutionary and epidemiological outcomes. Few studies have investigated tolerance in animals, and the extent of sexual dimorphism in tolerance is unknown. Using males and females from 50 Drosophila melanogaster genotypes, we investigated possible sources of genetic variation for immunity by assessing both resistance and tolerance to the common bacterial pathogen Pseudomonas aeruginosa. We found evidence of sexual dimorphism and sexual antagonism for resistance and tolerance, and a trade-off between the two traits. Our findings suggest that antagonistic pleiotropy may be a major contributor to variation in immunity, with implications for host–parasite coevolution.

Sexual Selection and the Random Union of Gametes: Testing for a Correlation in Fitness between Mates in Drosophila melanogaster

Both males and females vary in fitness. While high‐fitness males typically have greater siring success, it is not clear whether these males sire an equal fraction of offspring from all females or a disproportionately large fraction with high‐fitness females. The latter nonrandom reproductive pattern can arise as the result of sexual selection and creates a positive correlation in fitness between mates. Such a correlation, if it reflects a positive genetic correlation between mates with respect to fitness, increases the efficiency of selection, reducing mutation load and speeding adaptation. While there is evidence from many taxa that assortative mating for fitness may occur, these studies typically focus on observed matings rather than realized reproductive output. Here, we examine assortative mating for fitness in Drosophila melanogaster, first in the context of virgin matings and then using a measure of realized reproduction that incorporates remating and postcopulatory processes. We find evidence for positive assortative mating among virgins but no evidence of assortative mating using the more complete measure of reproduction.

Local Adaptation Interacts with Expansion Load during Range Expansion: Maladaptation Reduces Expansion Load

The biotic and abiotic factors that facilitate or hinder species range expansions are many and complex. We examine the impact of two genetic processes and their interaction on fitness at expanding range edges: local maladaptation resulting from the presence of an environmental gradient and expansion load resulting from increased genetic drift at the range edge. Results from spatially explicit simulations indicate that the presence of an environmental gradient during range expansion reduces expansion load; conversely, increasing expansion load allows only locally adapted populations to persist at the range edge. Increased maladaptation reduces the speed of range expansion, resulting in less genetic drift at the expanding front and more immigration from the range center, therefore reducing expansion load at the range edge. These results may have ramifications for species being forced to shift their ranges because of climate change or other anthropogenic changes. If rapidly changing climate leads to faster expansion as populations track their shifting climatic optima, populations may suffer increased expansion load beyond previous expectations.

Relative Effectiveness of Mating Success and Sperm Competition at Eliminating Deleterious Mutations in Drosophila melanogaster

Condition-dependence theory predicts that sexual selection will facilitate adaptation by selecting against deleterious mutations that affect the expression of sexually selected traits indirectly via condition. Recent empirical studies have provided support for this prediction; however, their results do not elucidate the relative effects of pre- and postcopulatory sexual selection on deleterious mutations. We used the Drosophila melanogaster model system to discern the relative contributions of pre- and postcopulatory processes to selection against deleterious mutations. To assess second-male ejaculate competition success (P2; measured as the proportion of offspring attributable to the experimental male) and mating success, mutant and wild-type male D. melanogaster were given the opportunity to mate with females that were previously mated to a standard competitor male. This process was repeated for males subjected to a diet quality manipulation to test for effects of environmentally-manipulated condition on P2 and mating success. While none of the tested mutations affected P2, there was a clear effect of condition. Conversely, several of the mutations affected mating success, while condition showed no effect. Our results suggest that precopulatory selection may be more effective than postcopulatory selection at removing deleterious mutations. The opposite result obtained for our diet manipulation points to an interesting discrepancy between environmental and genetic manipulations of condition, which may be explained by the multidimensionality of condition. Establishing whether the various stages of sexual selection affect deleterious mutations differently, and to what extent, remains an important issue to resolve.

SENSITIVITY OF THE DISTRIBUTION OF MUTATIONAL FITNESS EFFECTS TO ENVIRONMENT, GENETIC BACKGROUND, AND ADAPTEDNESS: A CASE STUDY WITH DROSOPHILA

Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s).

Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum

Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.