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Although it is well established theoretically that selective interference among mutations (Hill-Robertson interference) favours meiotic recombination, genomewide mean rates of mutation and strengths of selection appear too low to support this as the mechanism favouring recombination in nature. A possible solution to this discrepancy between theory and observation is that selection is at least intermittently very strong due to the antagonistic coevolution between a host and its parasites. The Red Queen theory posits that such coevolution generates fitness epistasis among loci, which generates negative linkage disequilibrium among beneficial mutations, which in turn favours recombination. This theory has received only limited support. However, Red Queen dynamics without epistasis may provide the ecological conditions that maintain strong and frequent selective interference in finite populations that indirectly selects for recombination. This hypothesis is developed here through the simulation of Red Queen dynamics. This approach required the development of a method to calculate the exact frequencies of multilocus haplotypes after recombination. Simulations show that recombination is favoured by the moderately weak selection of many loci involved in the interaction between a host and its parasites, which results in substitution rates that are compatible with empirical estimates. The model also reproduces the previously reported rapid increase in the rate of outcrossing in Caenorhabditis elegans coevolving with a bacterial pathogen. [ABSTRACT FROM AUTHOR]

Genetic interactions can play an important role in the evolution of reproductive strategies. In particular, negative dominance-by-dominance epistasis for fitness can theoretically favour sex and recombination. This form of epistasis can be detected statistically because it generates nonlinearity in the relationship between fitness and inbreeding coefficient. Measures of fitness in progressively inbred lines tend to show limited evidence for epistasis. However, tests of this kind can be biased against detecting an accelerating decline due to line losses at higher inbreeding levels. We tested for dominance-by-dominance epistasis in Drosophila melanogaster by examining viability at five inbreeding levels that were generated simultaneously, avoiding the bias against detecting nonlinearity that has affected previous studies. We find an accelerating rate of fitness decline with inbreeding, indicating that dominance-by-dominance epistasis is negative on average, which should favour sex and recombination. [ABSTRACT FROM AUTHOR]

The lack of evolutionary response to selection on mitochondrial genes through males predicts the evolution of nuclear genetic influence on male-specific mitochondrial function, for example by gene duplication and evolution of sex-specific expression of paralogs involved in metabolic pathways. Intergenomic epistasis may therefore be a prevalent feature of the genetic architecture of male-specific organismal function. Here, we assess the role of mitonuclear genetic variation for male metabolic phenotypes [metabolic rate and respiratory quotient (RQ)] associated with ejaculate renewal, in the seed beetle Callosobruchus maculatus, by assaying lines with crossed combinations of distinct mitochondrial haplotypes and nuclear lineages. We found a significant increase in metabolic rate following mating relative to virgin males. Moreover, processes associated with ejaculate renewal showed variation in metabolic rate that was affected by mitonuclear interactions. Mitochondrial haplotype influenced mating-related changes in RQ, but this pattern varied over time. Mitonuclear genotype and the energy spent during ejaculate production affected the weight of the ejaculate, but the strength of this effect varied across mitochondrial haplotypes showing that the genetic architecture of male-specific reproductive function is complex. Our findings unveil hitherto underappreciated metabolic costs of mating and ejaculate renewal, and provide the first empirical demonstration of mitonuclear epistasis on male reproductive metabolic processes. [ABSTRACT FROM AUTHOR]

RNA viruses are the main source of emerging infectious diseases because of the evolutionary potential bestowed by their fast replication, large population sizes and high mutation and recombination rates. However, an equally important property, which is usually neglected, is the topography of the fitness landscape. How many fitness maxima exist and how well they are connected is especially interesting, as this determines the number of accessible evolutionary pathways. To address this question, we have reconstructed a region of the fitness landscape of tobacco etch potyvirus constituted by mutations observed during the experimental adaptation of the virus to the novel host Arabidopsis thaliana. Fitness was measured for many genotypes and showed the existence of multiple peaks and holes in the landscape. We found prevailing epistatic effects between mutations, with cases of reciprocal sign epistasis being common among pairs of mutations. We also found that high-order epistasis was as important as pairwise epistasis in their contribution to fitness. Therefore, results suggest that the landscape was rugged due to the existence of holes caused by lethal genotypes, that a very limited number of potential neutral paths exist and that it contained a single adaptive peak. [ABSTRACT FROM AUTHOR]

Fitness valleys, in which mutations at different loci are singly deleterious but jointly beneficial, arise because of reciprocal sign epistasis. Recent theoretical work provides analytical approximations of times to cross fitness valleys via three mechanisms: sequential fixation, stochastic tunnelling and recombination. These times depend critically on the effective population size ( Ne). Human immunodeficiency virus type 1 (HIV-1) encounters fitness valleys in adapting to its secondary cell-surface chemokine coreceptor, CXCR4. Adaptation to CXCR4 tends to occur late in infection and only in about 50% of patients and is associated with disease progression. It has been hypothesized that the need to cross fitness valleys may explain the delayed and inconsistent adaptation to CXCR4. We have identified four fitness valleys from a previous study of fitness epistasis in adaptation to CXCR4 and use estimates of the within-patient variance Ne for different patient treatment statuses and infection stages (conditions) to estimate times to cross the valleys. These valleys may be crossed predominantly by stochastic tunnelling, although mean crossing times are consistently longer than the durations of the conditions for which they are calculated. These results were confirmed with stochastic simulation. Simulations show that crossing times for a given condition are highly variable and that for each condition there is a low probability of crossing each valley. These findings support the hypothesis that fitness valleys constrain the adaptation of HIV-1 to CXCR4. This study provides the first detailed analysis of the evolutionary dynamics associated with empirical fitness valleys. [ABSTRACT FROM AUTHOR]

Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution. [ABSTRACT FROM AUTHOR]

The fitness of populations adapting to new environments is expected to decline in different environments, but empirical studies often do not lend support for such adaptation costs. We test the idea that the initial fitness of the selected populations in the environment where the cost is estimated is key for interpreting tests of ecological trade-offs. We isolated single clones of the yeast Saccharomyces cerevisiae every ~250 generations from replicate experimental lineages that had been selected during 5000 generations in a glucose-limited environment. We then selected these clones in a galactose-limited environment for ~120 generations. Finally, we estimated single-clone fitness in both environments, before and after selection on galactose. The pleiotropic effects on glucose of selection on galactose evolved from positive to negative as fitness in glucose increased, providing strong support for the importance of initial fitness for determining the sign and magnitude of pleiotropic effects. This demonstrates that the sign of pleiotropic effects for fitness following adaptation to a new environment can change during long-term adaptation to an original environment. We also found no relationship between the size of the fitness changes in galactose and glucose, such that pleiotropic effects in glucose became relatively smaller as the sizes of direct effects on galactose increased. [ABSTRACT FROM AUTHOR]

Hybrid incompatibilities, measured as mortality and sterility, are caused by the disruption of gene interactions. They are important post-zygotic isolation barriers to species hybridization, and much effort is put into the discovery of the genes underlying these incompatibilities. In hybridization studies of the haplodiploid parasitic wasp genus Nasonia, genic incompatibilities have been shown to affect mortality and sterility. The genomic regions associated with mortality have been found to depend on the cytotype of the hybrids and thus suggest cytonuclear incompatibilities. As environmental conditions can affect gene expression and gene interaction, we here investigate the effect of developmental temperature on sterility and mortality in Nasonia hybrids. Results show that extreme temperatures strongly affect both hybrid sterility (mainly spermatogenic failure) and mortality. Molecular mapping revealed that extreme temperatures increase transmission ratio distortion of parental alleles at incompatible loci, and thus, cryptic incompatible loci surface under temperature stress that remain undiscovered under standard temperatures. Our results underline the sensitivity of hybrid incompatibilities to environmental factors and the effects of unstable epistasis. [ABSTRACT FROM AUTHOR]

Small population size is expected to induce heterosis, due to the random fixation and accumulation of mildly deleterious mutations, whereas within-population inbreeding depression should decrease due to increased homozygosity. Population bottlenecks, although less effective, may have similar consequences. We tested this hypothesis in the self-fertile freshwater snail Lymnaea stagnalis, by subjecting experimental populations to a single bottleneck of varied magnitude. Although patterns were not strong, heterosis was significant in the most severely bottlenecked populations, under stressful conditions. This was mainly due to hatching rate, suggesting that early acting and highly deleterious alleles were involved. Although L. stagnalis is a preferential outcrosser, inbreeding depression was very low and showed no clear relationship with bottleneck size. In the less reduced populations, inbreeding depression for hatching success increased under high inbreeding. This may be consistent with the occurence of synergistic epistasis between fitness loci, which may contribute to favour outcrossing in L. stagnalis. [ABSTRACT FROM AUTHOR]

It is well known that standard population genetic theory predicts decreased additive genetic variance ( Va) following a population bottleneck and that theoretical models including interallelic and intergenic interactions indicate such loss may be avoided. However, few empirical data from multicellular model systems are available, especially regarding variance/covariance (V/CV) relationships. Here, we compare the V/CV structure of seventeen traits related to body size and composition between control (60 mating pairs/generation) and bottlenecked (2 mating pairs/generation; average F = 0.39) strains of mice. Although results for individual traits vary considerably, multivariate analysis indicates that Va in the bottlenecked populations is greater than expected. Traits with patterns and amounts of epistasis predictive of enhanced Va also show the largest deviations from additive expectations. Finally, the correlation structure of weekly weights is not significantly different between control and experimental lines but correlations between necropsy traits do differ, especially those involving the heart, kidney and tail length. [ABSTRACT FROM AUTHOR]

In Drosophila melanogaster, the DDT resistance allele (DDT-R) is beneficial in the presence of DDT. Interestingly, DDT-R also elevates female fitness in the absence of DDT and existed in populations before DDT use. However, DDT-R did not spread regardless of DDT-independent selective advantages in females. We ask whether sexual antagonism could explain why DDT-R did not spread before pesticide use. We tested pre- and post-copulatory male fitness correlates in two genetic backgrounds into which we backcrossed the DDT-R allele. We found costs to DDT-R that depended on the genetic background in which DDT-R was found and documented strong epistasis between genetic background and DDT-R that influenced male size. Although it remains unclear whether DDT-R is generally sexually antagonistic, or whether the fitness costs noted would be sufficient to retard the spread of DDT-R in the absence of DDT, general fitness advantages to DDT-R in the absence of DDT may be unlikely. [ABSTRACT FROM AUTHOR]

Epistatic interactions between mutations are thought to play a crucial role in a number of evolutionary processes, including adaptation and sex. Evidence for epistasis is abundant, but tests of general theoretical models that can predict epistasis are lacking. In this study, I test the ability of metabolic control theory to predict epistasis using a novel experimental approach that combines phenotypic and genetic perturbations of enzymes involved in gene expression and protein synthesis in the bacterium Pseudomonas aeruginosa. These experiments provide experimental support for two key predictions of metabolic control theory: (i) epistasis between genes involved in the same pathway is antagonistic; (ii) epistasis becomes increasingly antagonistic as mutational severity increases. Metabolic control theory is a general theory that applies to any set of genes that are involved in the same linear processing chain, not just metabolic pathways, and I argue that this theory is likely to have important implications for predicting epistasis between functionally coupled genes, such as those involved in antibiotic resistance. Finally, this study highlights the fact that phenotypic manipulations of gene activity provide a powerful method for studying epistasis that complements existing genetic methods. [ABSTRACT FROM AUTHOR]

One of the two main hypotheses to account for ageing is antagonistic pleiotropy (AP). This model requires alleles that increase vital rates (reproduction or survival) at early age at the expense of vital rates at late age. An important focus of evolutionary studies has been to assess the relative abundance of AP-type aging alleles that arise through mutation. Here, we develop theory that predicts that senescence per se reduces the probability that these alleles arise by mutation. A direct result is that these mutations should arise with extremely low frequencies in already senescing populations. This has profound implications for the evolution of life histories because it implies that the adaptive evolution of aging via AP will experience negative feedback. This theory also clarifies the previously inexplicable epistatic patterns of genetic covariance across age-specific vital rates that are observed in mutation accumulation experiments. We show that this epistasis is an emergent property of aging. [ABSTRACT FROM AUTHOR]

Support for the theory of ecological speciation requires evidence for ecological divergence between species which directly or indirectly causes reproductive isolation. This study investigates effects of ecological vs. genetic disparity of parental species on the presence of endogenous selection (deformation and mortality rates) and potential sources of exogenous selection (growth rates and hatch timing) on hybrids. Hybrid embryonic development is analysed in a common-garden full-sib cross of three species belonging to two different ecotypes within the Coregonus lavaretus species flock in the central Alpine region of Europe. Although hatch timing was similar across the three species, embryonic growth rates and egg sizes differed between ecotypes. This led to a mismatch between embryonic growth rate and egg size in hybrid crosses that reveals epistasis between the maternal and embryonic genomes and transgressive hatch times that were asynchronous with control crosses. A strong constraint of egg size to embryo size at late development was also evident. We argue that this demonstrates potential for coadaptation of a maternal trait (egg size) with offspring growth rate to be an important source of selection against hybridization between ecotypes with different egg sizes. Implications for the measurement and quantification of early life-history traits affected by this additive relationship, such as hatch day and larval size, are also discussed. [ABSTRACT FROM AUTHOR]

The evolutionary effects of epistasis have been primarily explored analytically and most empirical studies have utilized yeast, viral and bacterial populations. Empirical analyses in multi-cellular organisms are rare because of experimental constraints. Here, we report the results of a genome-wide scan for two-way epistasis in 16 traits related to body size and composition in F2 mice from the LG/J by SM/J intercross. We analyze two-locus genotypic values at quantitative trait loci (QTL), which provides an especially detailed view of epistatic architectures, to evaluate their predicted evolutionary consequences via Monte Carlo simulations. Epistatic profiles vary, but all traits show complicated genetic architectures which are largely hidden in single locus QTL scans. On average, detected epistatic effects are comparable in size to marginal effects. Simulations demonstrate an expected preservation, and often inflation, of heritable variance across several generations of small effective population size for many identified epistatic pairs over a range of starting allele frequencies. [ABSTRACT FROM AUTHOR]

Epistasis is the nonadditive interaction between different loci which contribute to a phenotype. Epistasis between independent loci conferring insecticide resistance is important to investigate as this phenomenon can shape the rate that resistance evolves and can dictate the level of resistance in the field. The evolution of insecticide resistance in mosquitoes is a growing and world-wide problem. The two major mechanisms that confer resistance to permethrin in Culex mosquitoes are target site insensitivity (i.e. kdr) and enhanced detoxification by cytochrome P450 monooxygenases. Using three strains of mosquitoes, and crosses between these strains, we assessed the relative contribution of the two independent loci conferring permethrin resistance, individually and when present together. We found that for all genotype combinations tested, Culex pipiens quinquefasciatus exhibited multiplicative interactions between kdr and P450 detoxification, whether the resistance alleles were homozygous or heterozygous. These results provide a basis for further analysis of the evolution and maintenance of insecticide resistance in mosquitoes. [ABSTRACT FROM AUTHOR]

Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles. Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study of inbreeding-related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two QTL on the major autosomes carrying recessive lethals that caused male mortality, one of which also affected female mortality. More detailed study of these loci will provide information on the mechanistic basis and environmental sensitivity of inbreeding depression. [ABSTRACT FROM AUTHOR]

Replicated lines of Drosophila subobscura originating from a large outbred stock collected at the estimated Chilean epicentre (Puerto Montt) of the original New World invasion were allowed to evolve under controlled conditions of larval crowding for 3.5 years at three temperature levels (13, 18 and 22 °C). Several pre-adult life history traits (development time, survival and competitive ability), adult life history related traits (wing size, wing shape and wing-aspect ratio), and wing size and shape asymmetries were measured at the three temperatures. Cold-adapted (13 °C) populations evolved longer development times and showed lower survival at the highest developmental temperature. No divergence for wing size was detected following adaptation to temperature extremes (13 and 22 °C), in agreement with earlier observations, but wing shape changes were obvious as a result of both thermal adaptation and development at different temperatures. However, the evolutionary trends observed for the wing-aspect ratio were inconsistent with an adaptive hypothesis. There was some indication that wing shape asymmetry has evolutionarily increased in warm-adapted populations, which suggests that there is additive genetic variation for fluctuating asymmetry and that it can evolve under rapid environmental changes caused by thermal stress. Overall, our results cast strong doubts on the hypothesis that body size itself is the target of selection, and suggest that pre-adult life history traits are more closely related to thermal adaptation. [ABSTRACT FROM AUTHOR]

Crosses between populations of Tigriopus californicus result in backcross and F2 hybrid breakdown for a variety of fitness related measures. The magnitude of this hybrid breakdown is correlated with evolutionary divergence. We assessed the chromosomal basis of viability differences in nonrecombinant backcross hybrids using markers mapped to individual chromosomes. To assess effects of evolutionary divergence we crossed one population to three different populations: two distantly related (∼18% mitochondrial COI sequence divergence) and one closely related (∼1% mitochondrial COI sequence divergence). We found that all three interpopulation crosses resulted in significant deviations from expected Mendelian ratios at a majority of the loci studied. In all but one case, deviations were due to a deficit of parental homozygotes. This pattern implies that populations of T. californicus carry a significant genetic load, and that a combination of beneficial dominance and deleterious homozygote–heterozygote interactions significantly affects hybrid viability. Pairwise tests of linkage disequilibrium detected relatively few significant interactions. For the two divergent crosses, effects of individual chromosomes were highly concordant. These two crosses also showed higher heterozygote excess in females than males across the vast majority of chromosomes. [ABSTRACT FROM AUTHOR]

Inbreeding depression is one of the hypotheses explaining the maintenance of females within gynodioecious plant populations. However, the measurement of fitness components in selfed and outcrossed progeny depends on life-cycle stage and the history of inbreeding. Comparative data indicate that strong inbreeding depression is more likely to occur at later life-cycle stages. We used hermaphrodite individuals of Silene vulgaris originating from three populations located in different valleys in the Swiss Alps to investigate the effect of two generations of self- and cross-fertilization on fitness components among successive stages of the life cycle in a glasshouse experiment. We detected significant inbreeding depression for most life-cycle stages including: the number of viable and aborted seeds per fruit, probability of germination, above ground biomass, probability of flowering, number of flowers per plant, flower size and pollen viability. Overall, the intensity of inbreeding depression increased among successive stages of the life cycle and cumulative inbreeding depression was significantly stronger in the first generation ( δ ≈ 0.5) compared with the second generation ( δ ≈ 0.35). We found no evidence for synergistic epistasis in our experiment. Our finding of more intense inbreeding depression during later stages of the life cycle may help to explain the maintenance of females in gynodioecious populations of S. vulgaris because purging of genetic load is less likely to occur. [ABSTRACT FROM AUTHOR]

Comma butterflies (Nymphalidae: Polygonia c-album L.) from one Belgian site and three Spanish sites were crossed with butterflies from a Swedish population in order to investigate inheritance of female host plant choice, egg mass and larval growth rate. We found three different modes of inheritance for the three investigated traits. In line with earlier results from crosses between Swedish and English populations, the results regarding female oviposition preference (choice between Urtica dioica and Salix caprea) showed X-linked inheritance to be of importance for the variation between Sweden and the other sites. Egg mass and growth rate did not show any sex-linked inheritance. Egg mass differences between populations seem to be controlled mainly by additive autosomal genes, as hybrids showed intermediate values. The growth rates of both hybrid types following reciprocal crossings were similar to each other but consistently higher than for the two source populations, suggesting a nonadditive mode of inheritance which is not sex-linked. The different modes of inheritance for host plant preference vs. important life history traits are likely to result in hybrids with unfit combinations of traits. This type of potential reproductive barrier based on multiple ecologically important traits deserves more attention, as it should be a common situation for instance in the early stages of population divergence in host plant usage, facilitating ecological speciation. [ABSTRACT FROM AUTHOR]

In order to detect possible synergistic epistasis for viability in Drosophila melanogaster we assayed the relative viability of chromosomes II in: (i) panmixia, (ii) forced total homozygosity, and (iii) homozygosity for, on the average, half of their loci. As these genotypes were constructed using exactly the same set of chromosomes in the three cases, the design allows us to estimate the inbreeding depression rate at two different inbreeding levels in the absence of purging natural selection. Overall, no consistent synergistic epistasis was found. However, there was a small fraction of chromosomes whose severely deleterious effect when homozygous was almost significantly larger than expected from their viability when homozygous for half of their loci. This suggests occasional but important synergistic epistasis, which might confer evolutionary advantage to recombination in tightly linked genomes. Nevertheless, such epistasis is unlikely to be an evolutionary advantage driving the evolution of sexual anisogamous reproduction, as its contribution to overall viability is small when compared with the two-fold cost of anisogamy. [ABSTRACT FROM AUTHOR]

In many groups of organisms the location of settling is determined by competition, and fitter individuals tend to settle closer to their natal territory than less fit ones. In this work we study the implications of this phenomenon to the problem of adaptation and speciation on a rugged adaptive landscape. One consequence of fitness-associated dispersal (FAD) is that individuals with high fitness are more likely to experience inbreeding, especially with other fit individuals. Another consequence is that when dispersal is costly, the less fit individuals are more likely to pay the cost. When a rare and advantageous allelic combination appears, FAD may increase its chances to spread in the population. In a two-locus two-alleles model with negative epistasis, we find that FAD significantly shortens the waiting time for an adaptive peak shift in comparison with random dispersal. [ABSTRACT FROM AUTHOR]

Behavioural interactions are often analysed in terms of their costs and benefits to the actors [Hamilton, (1964) J. Theor. Biol. 7 1–16; Gadagkar, (1993) Trends Ecol. Evol. 8 232–234; Foster et al., (2001) Ann. Zool. Fenn. 38 229–238]. Using the bumblebee Bombus terrestris, we wish to distinguish between two possible determinants of interaction behaviour between conspecifics, namely kindirected behaviour that reflects genetic distance between individuals, or, alternatively, interactions guided by a functional distance between individuals, specifically, with respect to disease susceptibility. We find no relationship between contact rate of individuals and the genetic distance of their respective colonies. Interestingly, we do find a significant negative correlation between contact rate and the distance between the two colonies in susceptibility to a spectrum of parasite strains. This cannot be explained by either of the a priori alternatives so we propose two further testable hypotheses to explain our results. [ABSTRACT FROM AUTHOR]

The frozen niche variation hypothesis proposes that asexual clones exploit a fraction of a total resource niche available to the sexual population from which they arise. Differences in niche breadth may allow a period of coexistence between a sexual population and the faster reproducing asexual clones. Here, we model the longer term threat to the persistence of the sexual population from an accumulation of clonal diversity, balanced by the cost to the asexual population resulting from a faster rate of accumulation of deleterious mutations. We use Monte-Carlo simulations to quantify the interaction of niche breadth with accumulating deleterious mutations. These two mechanisms may act synergistically to prevent the extinction of the sexual population, given: (1) sufficient genetic variation, and consequently niche breadth, in the sexual population; (2) a relatively slow rate of accumulation of genetic diversity in the clonal population; (3) synergistic epistasis in the accumulation of deleterious mutations. [ABSTRACT FROM AUTHOR]

Litter size is an important reproductive trait as it makes a major contribution to fitness. Generally, traits closely related to fitness show low heritability perhaps because of the corrosive effects of directional natural selection on the additive genetic variance. Nonetheless, low heritability does not imply, necessarily, a complete absence of genetic variation because genetic interactions (epistasis and dominance) contribute to variation in traits displaying strong heterosis in crosses, such as litter size. In our study, we investigated the genetic architecture of litter size in 166 females from an F2 intercross of the SM/J and LG/J inbred mouse strains. Litter size had a low heritability ( h2 = 12%) and a low repeatability ( r = 33%). Using interval-mapping methods, we located two quantitative trait loci (QTL) affecting litter size at locations D7Mit21 + 0 cM and D12Mit6 + 8 cM, on chromosomes 7 and 12 respectively. These QTL accounted for 12.6% of the variance in litter size. In a two-way genome-wide epistasis scan we found eight QTL interacting epistatically involving chromosomes 2, 4, 5, 11, 14, 15 and 18. Taken together, the QTL and their interactions explain nearly 49% (39.5% adjusted multiple r2) of the phenotypic variation for litter size in this cross, an increase of 36% over the direct effects of the QTL. This indicates the importance of epistasis as a component of the genetic architecture of litter size and fitness in our intercross population. [ABSTRACT FROM AUTHOR]

Epistasis results when the fitness effects of a mutation change depending on the presence or absence of other mutations in the genome. The predictions of many influential evolutionary hypotheses are determined by the existence and form of epistasis. One rich source of data on the interactions among deleterious mutations that has gone untapped by evolutionary biologists is the literature on the design of live, attenuated vaccine viruses. Rational vaccine design depends upon the measurement of individual and combined effects of deleterious mutations. In the current study, we have reviewed data from 29 vaccine-oriented studies using 14 different RNA viruses. Our analyses indicate that (1) no consistent tendency towards a particular form of epistasis exists across RNA viruses and (2) significant interactions among groups of mutations within individual viruses occur but are not common. RNA viruses are significant pathogens of human disease, and are tractable model systems for evolutionary studies – we discuss the relevance of our findings in both contexts. [ABSTRACT FROM AUTHOR]

In this mini-review, I discuss the effects of gene interaction or epistasis from a `gene's eye view.' By a `gene's eye view' of epistasis, I mean that I will consider a single, bi-allelic locus, A , whose effects on fitness result only from its interactions with alleles of another, unknown locus, X . I will show how changes in the frequencies of alleles at the background locus affect the relationship of alleles at the A -locus to fitness. Changing the genetic background changes the fundamental characteristics of the A -locus, such as the magnitude and sign of allelic effects on fitness, and, consequently, it changes the strength and pattern of selection. I consider each of the four kinds of pair–wise interactions between two loci and show that some kinds of epistasis are more sensitive than others to population genetic subdivision. Lastly, I show that some kinds of epistasis are more likely than others to affect the process of speciation and contribute to or be responsible for general genetic features of interspecific hybrids, such as Haldane's rule. [ABSTRACT FROM AUTHOR]

Salathé and Ebert (2003,J. Evol. Biol.16:976–985) have shown that the mean logarithmic fitness ofDaphnia magnaclones declined faster than linearly with increasing inbreeding coefficientF. They interpreted this result as evidence for synergistic epistasis. Trouveet al.(2004, J. Evol. Biol., doi: 10.1111/j.1420-9101.2004.00755.x) suggested that hybrid vigour could be an alternative explanation for this finding. We use a population genetic model to support the original claim that the marked deviation from linearity cannot be explained without epistasis. We further argue that the relevant reference population is the metapopulation and not the subpopulation. Taken together, we believe that synergistic epistasis between recessive deleterious alleles segregating in theD. magnametapopulation is the most likely explanation for the finding of Salathé and Ebert. [ABSTRACT FROM AUTHOR]

Inbreeding generally results in deleterious shifts in mean fitness. If the fitness response to increasing inbreeding coefficient is non-linear, this suggests a contribution of epistasis to inbreeding depression. In a cross-breeding experiment, Salathé&Ebert (2003.J. Evol. Biol.16: 976–985) tested and found the presence of this non-linearity inDaphnia magna. They argue that epistatic interactions cause this non-linearity. We argue here that their experimental protocol does not allow disentangling the effect of synergistic epistasis from two alternative hypotheses, namely hybrid vigour and statistical non-independence of data. [ABSTRACT FROM AUTHOR]