Epistatic Variance Research Articles

Identifying Quantitative Trait Locus by Genetic Background Interactions in Association Studies

Association studies are designed to identify main effects of alleles across a potentially wide range of genetic backgrounds. To control for spurious associations, effects of the genetic background itself are often incorporated into the linear model, either in the form of subpopulation effects in the case of structure or in the form of genetic relationship matrices in the case of complex pedigrees. In this context epistatic interactions between loci can be captured as an interaction effect between the associated locus and the genetic background. In this study I developed genetic and statistical models to tie the locus by genetic background interaction idea back to more standard concepts of epistasis when genetic background is modeled using an additive relationship matrix. I also simulated epistatic interactions in four-generation randomly mating pedigrees and evaluated the ability of the statistical models to identify when a biallelic associated locus was epistatic to other loci. Under additive-by-additive epistasis, when interaction effects of the associated locus were quite large (explaining 20% of the phenotypic variance), epistasis was detected in 79% of pedigrees containing 320 individuals. The epistatic model also predicted the genotypic value of progeny better than a standard additive model in 78% of simulations. When interaction effects were smaller (although still fairly large, explaining 5% of the phenotypic variance), epistasis was detected in only 9% of pedigrees containing 320 individuals and the epistatic and additive models were equally effective at predicting the genotypic values of progeny. Epistasis was detected with the same power whether the overall epistatic effect was the result of a single pairwise interaction or the sum of nine pairwise interactions, each generating one ninth of the epistatic variance. The power to detect epistasis was highest (94%) at low QTL minor allele frequency, fell to a minimum (60%) at minor allele frequency of about 0.2, and then plateaued at about 80% as alleles reached intermediate frequencies. The power to detect epistasis declined when the linkage disequilibrium between the DNA marker and the functional polymorphism was not complete.

THE CHANGE IN QUANTITATIVE GENETIC VARIATION WITH INBREEDING

Inbreeding is known to reduce heterozygosity of neutral genetic markers, but its impact on quantitative genetic variation is debated. Theory predicts a linear decline in additive genetic variance (V(A)) with increasing inbreeding coefficient (F) when loci underlying the trait act additively, but a nonlinear hump-shaped relationship when dominance and epistasis are important. Predictions for heritability (h2) are similar, although the exact shape depends on the value of h2 in the absence of inbreeding. We located 22 published studies in which the level of genetic variation in experimentally inbred populations (measured by V(A) or h2) was compared with that in outbred control populations. For life-history traits, the data strongly supported a nonlinear change in genetic variation with increasing F. V(A) and h2 were, respectively, 244% and 50% higher at F = 0.4 than in outbred populations, and dominance plus epistatic variance together exceeded additive variance by a factor of four. For nonfitness traits the decline was linear and estimates of nonadditive variance were small. These results confirm that population bottlenecks frequently increase V(A) in some traits, and imply that life-history traits are underlain by substantial dominance or epistasis. However, the importance of drift-induced genetic variation in conservation or evolutionary biology is questionable, in part because inbreeding depression usually accompanies inbreeding.

Extension of the concept of kinship, relationship, and inbreeding to account for linked epistatic complexes

Abstract Although epistatic effects are well defined and, in principle, can be exploited in quantitative-genetic selection theory, they often are ignored or even treated as nuisance parameters in practical applications. Traditionally, epistasis is considered as an interaction between genes at unspecified loci. Inspired by the observation that functional genes are often organised in physical clusters, we developed a model to combine additive effects and additive × additive interactions in linked gene clusters of defined length. Malecot's kinship concept is extended to identity by descent probabilities for chromosome segments of a given length in Morgan units, called epistatic kinship. Using the analogy of Malecot's kinship and Wright's relationship and inbreeding coefficients, epistatic relationship coefficients and epistatic inbreeding coefficients are defined. Simple rules are given to set up the epistatic numerator relationship matrix and its inverse directly from a pedigree list. The well-known single locus parameters and algorithms to set up the additive numerator relationship matrix and its inverse are a special case of the suggested methodology for a chromosome segment length of null Morgan. A proof of concept of the suggested method is given with a small simulation study. Assuming additive, linked epistatic and residual variance components, 100 replicated data sets for 1000 individuals are generated. From these data, residual maximum likelihood estimates of the variance components and of the chromosome segment size are obtained. Potential applications of the methodology are discussed. Given that a substantial variance component is attributed to this effect, the expected genetic gain can be increased on the short term if selection is on additive and epistatic effects, the latter comprising additive × additive interaction effect of loci in linkage disequilibrium. This extra benefit, however, will diminish through crossing over in subsequent generations. Despite some practical problems yet to be solved, the suggested model and algorithms open new perspectives to use a higher proportion of genetic variability in selection and breeding.

CYTO-NUCLEAR EPISTASIS: TWO-LOCUS RANDOM GENETIC DRIFT IN HERMAPHRODITIC AND DIOECIOUS SPECIES

Abstract We report the findings of our theoretical investigation of the effect of random genetic drift on the covariance of identity-by-descent (ibd) of nuclear and cytoplasmic genes. The covariance in ibd measures of the degree to which cyto-nuclear gene combinations are heritable, that is, transmitted together from parents to offspring. We show how the mating system affects the covariance of ibd, a potentially important aspect of host-pathogen or host-symbiont coevolution. The magnitude of this covariance influences the degree to which the evolution of apparently neutral cytoplasmic genes, often used in molecular phylogenetics, might be influenced by selection acting on unlinked nuclear genes. To the extent that cyto-nuclear gene combinations are inherited together, genomic conflict is mitigated and intergenomic transfer it facilitated, because genes in both organelle and nuclear genomes share the same evolutionary fate. The covariance of ibd also affects the rate at which cyto-nuclear epistatic variance is converted to additive variance necessary for a response to selection. We find that conversion is biased in species with separate sexes, so that the increment of additive variance added to the nuclear genome exceeds that added to the cytoplasmic genome. As a result, the host might have an adaptive advantage in a coevolutionary arms race with vertically (maternally) transmitted pathogens. Similarly, the nuclear genome could be a source of compensatory mutations for its organellar genomes, as occurs in cytoplasmic male sterility in some plant species. We also discuss the possibility that adaptive cytoplasmic elements, such as favorable mitochondrial mutations or endosymbionts (e.g., Wolbachia), have the potential to release heritable nuclear variation as they sweep through a host population, supporting the view that cytoplasmic introgression plays an important role in adaptation and speciation.

CYTO-NUCLEAR EPISTASIS: TWO-LOCUS RANDOM GENETIC DRIFT IN HERMAPHRODITIC AND DIOECIOUS SPECIES

We report the findings of our theoretical investigation of the effect of random genetic drift on the covariance of identity-by-descent (ibd) of nuclear and cytoplasmic genes. The covariance in ibd measures of the degree to which cyto-nuclear gene combinations are heritable, that is, transmitted together from parents to offspring. We show how the mating system affects the covariance of ibd, a potentially important aspect of host-pathogen or host-symbiont coevolution. The magnitude of this covariance influences the degree to which the evolution of apparently neutral cytoplasmic genes, often used in molecular phylogenetics, might be influenced by selection acting on unlinked nuclear genes. To the extent that cyto-nuclear gene combinations are inherited together, genomic conflict is mitigated and intergenomic transfer it facilitated, because genes in both organelle and nuclear genomes share the same evolutionary fate. The covariance of ibd also affects the rate at which cyto-nuclear epistatic variance is converted to additive variance necessary for a response to selection. We find that conversion is biased in species with separate sexes, so that the increment of additive variance added to the nuclear genome exceeds that added to the cytoplasmic genome. As a result, the host might have an adaptive advantage in a coevolutionary arms race with vertically (maternally) transmitted pathogens. Similarly, the nuclear genome could be a source of compensatory mutations for its organellar genomes, as occurs in cytoplasmic male sterility in some plant species. We also discuss the possibility that adaptive cytoplasmic elements, such as favorable mitochondrial mutations or endosymbionts (e.g., Wolbachia), have the potential to release heritable nuclear variation as they sweep through a host population, supporting the view that cytoplasmic introgression plays an important role in adaptation and speciation.

The role of epistatic gene interactions in the response to selection and the evolution of evolvability

It has been argued that the architecture of the genotype–phenotype map determines evolvability, but few studies have attempted to quantify these effects. In this article we use the multilinear epistatic model to study the effects of different forms of epistasis on the response to directional selection. We derive an analytical prediction for the change in the additive genetic variance, and use individual-based simulations to understand the dynamics of evolvability and the evolution of genetic architecture. This shows that the major determinant for the evolution of the additive variance, and thus the evolvability, is directional epistasis. Positive directional epistasis leads to an acceleration of evolvability, while negative directional epistasis leads to canalization. In contrast, pure non-directional epistasis has little effect on the response to selection. One consequence of this is that the classical epistatic variance components, which do not distinguish directional and non-directional effects, are useless as predictors of evolutionary dynamics. The build-up of linkage disequilibrium also has negligible effects. We argue that directional epistasis is likely to have major effects on evolutionary dynamics and should be the focus of empirical studies of epistasis.

Dominance, epistasis, heritabilities and expected genetic gains

Although epistasis is common in gene systems that determine quantitative traits, it is usually not possible to estimate the epistatic components of genotypic variance because experiments in breeding programs include only one type of progeny. As the study of this phenomenon is complex, there is a lack of theoretical knowledge on the contribution of the epistatic variances when predicting gains from selection and on the bias in estimating genetic parameters when fitting the additive-dominant model. The objective of this paper is to discuss these aspects. Regarding a non-inbred population, the genetic value due to dominance and the epistatic components of the genotypic value are not indicators of the number of favorable genes present in an individual. Thus, the efficiency of a selection process should be based on the narrow-sense heritability, a function only of additive variance. If there is no epistasis, generally it is satisfactory to assess the selection efficiency and to predict gain based on the broad-sense heritability. Regardless of the selection unit or type of epistasis, the bias in the estimate of the additive variance when assuming the additive-dominant model is considerable. This implies overestimation of the heritabilities at half sib family mean, plant within family and plant levels, and underestimation if the selection units are full sib progenies. The predicted gains will have a bias proportional to that of the heritability.

The struggle to exploit non-additive variation

Whereas animal breeders largely focus on improvement using additive genetic variance, inbreeding and asexual reproduction allow plant breeders to at least partially exploit non-additive genetic variance as well. We briefly review various approaches used by breeders to exploit dominance and epistatic variance, discuss their constraints and limitations, and examine what (if anything) can be done to improve our ability to further use often untapped genetic variation.

Epistasis underlying a fitness trait within a natural population of the pitcher-plant mosquito, Wyeomyia smithii.

We selected on divergent photoperiodic response in three separate lines from a natural population of the pitcher-plant mosquito, Wyeomyia smithii. Line crosses reveal that there exists within a population, diverse epistatic variation for a fitness trait that could contribute to adaptive potential following founder events or rapid climate change.

Use of inbred sires to exploit epistatic variance (short communication)

Abstract. The genetic variance of inbred sires is increased and variance due to additive x additive effects proportionately more than that due to additive ones. In case of inbreeding by mating sire to daughters the time interval elite sire – son needs not to be elongated so that the genetic progress could be increased by this procedure. This pertains even more to the procedure. where inbred sires are produced from sib mating. Use of such sires should increase the genetic gain via the sire son path by about 10 %.

EFFECTS OF GENETIC DRIFT ON VARIANCE COMPONENTS UNDER A GENERAL MODEL OF EPISTASIS

We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(delta(z)) = sigma(n)k=1 FkV(A(k)), where n is the number of loci contributing to the trait variance, V(A(1)) = V(A) is the additive genetic variance, and V(A(k)) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*(A)), is closely related to var(delta(z)); (V*(A)) = (1 - F) sigma(n)k=1 kFk-1V(A(k)). Thus, epistasis inflates the expected additive variance above V(A)(1 - F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*(AA. This is not true in general with diploidy, because dominance alone can reduce (V*(A)) below V(A)(1 - F) (e.g., when dominant alleles are rare). Without dominance, diploidy produces simple expressions: var(delta(z)) = sigma(n)k=1 (2F)kV(A(k)) and (V(A)) = (1 - F) sigma(n)k=1 k(2F)k-1V(A(k)). With dominance (and even without epistasis), var(delta(z)) and (V*(A)) no longer depend solely on the variance components in the base population. For small F, the expected additive variance simplifies to (V*(A)) approximately equal to (1 - F)V(A) + 4FV(AA) + 2FV(D) + 2FC(AD), where C(AD) is a sum of two terms describing covariances between additive effects and dominance and additive X dominance interactions. Whether population bottlenecks lead to expected increases in additive variance depends primarily on the ratio of nonadditive to additive genetic variance in the base population, but dominance precludes simple predictions based solely on variance components. We illustrate these results using a model in which genotypic values are drawn at random, allowing extreme and erratic epistatic interactions. Although our analyses clarify the conditions under which drift is expected to increase V(A), we question the evolutionary importance of such increases.

Epistasis in Quantitative Trait Locus Linkage Analysis: Interaction or Main Effect?

This paper explores a two-locus variance components model of quantitative trait locus (QTL) linkage for sib-pairs that incorporates epistasis. For a range of epistatic models the expected variance components and noncentrality parameter per sib-pair can be calculated, to indicate the power to detect epistasis. In QTL linkage analysis, additive and epistatic effects are in fact partially confounded; as a result, variance components under incorrect submodels can be distorted, with two main implications. First, the analysis of a single locus can in fact detect a QTL that has no main effect but interacts epistatically with another (unmeasured) locus. That is, single-locus approaches do not necessarily preclude the detection of purely epistatically interacting loci. Second, because the nonepistatic variance component estimates in submodels can partially absorb epistatic variance when it is not explicitly modeled, power to formally detect epistasis is low.

Estimates of Additive, Dominance and Epistatic Genetic Variances from a Clonally Replicated Test of Loblolly Pine

Abstract Nine full-sib families were generated using a factorial mating design consisting of three female and three male loblolly pine (Pinus taeda L.) parents. Full-sib seedlings and clones of the same families were planted in two test sites in Alabama and Florida. Additive, dominance, and epistatic genetic variances were estimated for growth traits and for fusiform rust incidence for ages 1 through 6. Epistatic variances did not have a significant role in growth traits, but additive gene actions were the major source of genetic variance in loblolly pine. Dominance variance for height, diameter, and volume was negligible at early ages, but it was considerable at age 6, particularly for volume. Fusiform rust incidence appeared to be partially under additive and epistatic gene actions and genetic differences among the clones within families accounted for 48.6% of the total variance. Within-plot variance for clones was always smaller than that within-plot variance for seedlings of the same full-sib families. Clonally replicated progeny tests may provide special advantages for loblolly pine tree improvement programs, as they would substantially increase the efficiency of testing by reducing the microenvironmental variance and better estimation of genetic parameters. This may provide greater genetic gains, particularly for fusiform rust incidence. Potential effects of the small parental size and violations of the assumptions of the genetic model are discussed. Negative additive and nonadditive genetic correlations between the growth traits and fusiform rust incidence are encouraging for rapid and simultaneous improvement of the traits during the same cycle selection. FOR. SCI. 49(1):77–88.

Mapping quantitative trait loci with epistatic effects.

Epistatic variance can be an important source of variation for complex traits. However, detecting epistatic effects is difficult primarily due to insufficient sample sizes and lack of robust statistical methods. In this paper, we develop a Bayesian method to map multiple quantitative trait loci (QTLs) with epistatic effects. The method can map QTLs in complicated mating designs derived from the cross of two inbred lines. In addition to mapping QTLs for quantitative traits, the proposed method can even map genes underlying binary traits such as disease susceptibility using the threshold model. The parameters of interest are various QTL effects, including additive, dominance and epistatic effects of QTLs, the locations of identified QTLs and even the number of QTLs. When the number of QTLs is treated as an unknown parameter, the dimension of the model becomes a variable. This requires the reversible jump Markov chain Monte Carlo algorithm. The utility of the proposed method is demonstrated through analysis of simulation data.

Detection of epistasis, and estimation of additive and dominance components of genetic variation for synchrony in pod maturity in mungbean ( Vigna radiata (L.) Wilczek)

Genetics of days to first flowering, first pod maturity, 90% pod maturity, and duration of the period from first flower to 90% pod maturity (DDd 1) and from first pod maturity to 90% pod maturity (DDd 2) [degree of non-synchrony of pod maturity] were investigated in mungbean using the triple test cross (TTC) technique. Ten diverse genotypes were crossed with two true breeding testers ( L 1 and L 2) and the F 1 hybrid of the tester lines ( L 3). The resultant single and three-way crosses were evaluated in two seasons (kharif and spring/summer). Epistatic variation was found to be an integral part of inheritance of days to first flower in both seasons and days to first pod maturity only in kharif season. Further partitioning of total epistasis revealed that additive×additive ( i type) interactions had a major role in the inheritance of these traits. In the absence of epistasis both additive and dominance genetic components were significant for days to 90% pod maturity, DDd 1, and DDd 2 in both seasons, and for days to first flower in spring/summer season. The additive genetic component was predominant for days to 90% pod maturity and DDd 2 in both seasons and for DDd 1 in spring/summer season, whereas the dominance component was important for days to first flower and DDd 1 in the spring/summer season. The direction of dominance was towards early maturity of 90% pods and late maturity of the first pod. The significant additive genetic component in DDd 1 and DDd 2 could be exploited in later generations for developing mungbean genotypes with improved synchrony in pod maturity.

Genetic interactions maintain Y chromosome variation

The Drosophila melanogaster Y chromosome, comprising approximately an eighth of the total DNA content of males, appears much like a genetic junkyard filled with long stretches of heterochromatic repeats. Aside from the six giant lampbrush loops that are required for male fertility and some of the ribosomal DNA, the Y chromosome has few coding genes. Although males without Y chromosomes are sterile, they have high viability and appear morphologically indistinguishable from normal males. Several studies have shown that variation in the Y chromosome within D. melanogaster contributes little or nothing to genetic variation in fitness or morphological characteristics.Chippindale and Rice recently reported 1xY chromosome polymorphism is a strong determinant of male fitness in Drosophila melanogaster. Chippindale, A.K. and Rice, W.R. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 5677–5682Crossref | PubMed | Scopus (90)See all References1 a surprising result: substantial variation for fitness associated with the Y chromosome exists within a natural population of D. melanogaster. Indeed, in their study the Y contributes 68% as much variation as an entire X-autosome genomic haplotype. The primary effect of this Y chromosome variation is on male reproductive fitness, not on egg-to-adult viability. Differences in male reproductive fitness could reflect differences in sperm production or function (including sperm competition). Differential mating ability might also contribute to the differences in reproductive success. Segregation distortion is unlikely to be a major component of the observed differences.This study differs from previous ones in that they assayed the fitnesses of different Y chromosome lines in explicitly different genetic backgrounds. The authors’ sophisticated breeding design assured that sublines derived from the same main Y chromosome line would share exceedingly few X-linked or autosomal genes derived from common ancestors. Using these sublines, they then tested the fitnesses of each Y chromosome line in the genetic backgrounds of three different inbred lines. In each genetic background, some Y chromosome lines had much higher fitness than did others. Yet, the lines that did well in one genetic background tended to do poorly in the other genetic backgrounds. Averaged across these backgrounds, there was no significant additive genetic variation for fitness among Y chromosome lines, consistent with the previous studies. The interaction (epistatic) component accounted for the vast majority of the genetic variation.Chippindale and Rice's study has several implications for the evolution of Y chromosomes. For instance, the substantial epistatic genetic variation for fitness should promote the accumulation of new genetic material to the Y chromosome through genetic rearrangements. Their study might also have implications for speciation: between closely related species of Drosophila, divergence in Y chromosomes sometimes contributes to male sterility in hybrids because Y-linked changes in one species interact with autosomal or possibly X-linked changes in the other species. This study demonstrates that the negative interactions that lead to hybrid sterility between species might, to a lesser extent, already be present within species.

Phenotypic evolution and the genetic architecture underlying photoperiodic time measurement

A wide variety of higher plants, vertebrates, and arthropods use the length of day to synchronize growth, development, reproduction, dormancy, and migration with the changing seasons. In the pitcher-plant mosquito, Wyeomyia smithii, critical photoperiod mediating the onset and maintenance of larval diapause has evolved about 10 standard deviations in mean critical photoperiod between the ancestral, Gulf Coast populations, and the derived, Canadian populations. We are seeking to understand how this evolution has been accomplished at both the genetic and the physiological levels. At the genetic level, average heterozygosity at protein-coding loci decreases with latitude of origin, while genetic variation for photoperiodic response increases with latitude of origin, particularly within the formerly glaciated regions of North America. Hybridization experiments reveal widespread genetic differences in critical photoperiod due to epistasis. We ascribe the increase in genetic variation in photoperiodic response, despite directional and stabilizing selection to the contrary, to the release of additive from epistatic variance during successive founder events in W. smithii's northward dispersal following recession of the Laurentide Ice Sheet, and to the resulting genetic drift and reorganization of genetic architectures in descendent populations. At the physiological level, northern populations of W. smithii, as well as northern populations of spider mites, flies, moths, and beetles in both North America and Europe show a declining expression of the rhythmic component of photoperiodic response. In Drosophila melanogaster, when the epistatic coupling between the period locus and photoperiodic response is disrupted, the critical photoperiod is shifted towards shorter daylengths; analogously in W. smithii, when epistatic interactions are disrupted in the recombining generations of hybrid populations, the critical photoperiod is shifted towards shorter daylengths. The implications here are (1) that in W. smithii, it is the epistatic modification of the photoperiodic response curve by the circadian clock that is being disrupted in the recombining generations and (2) that post-glacial range expansion into the North-Temperate Zone by arthropods in general may involve uncoupling of the circadian and photoperiodic clocks. Despite the tremendous advances that have been made in understanding circadian rhythmicity at the molecular level, virtually nothing is known about how or whether any of the downstream ‘clock-controlled genes’ connect with photoperiodic time measurement. Except in W. smithii, little is known about how this connection changes with seasonal adaptation of photoperiodic response through evolutionary time. It is our goal and desire that our top–down approach to the evolution of photoperiodic time measurement will meet and mesh with the bottom–up approach that is being developed so fruitfully for circadian clocks.

Pine hybrids — a review of their use performance and genetics

Abstract Inter-specific hybrid trees planted throughout the world on a commercial basis are most common in the genera Acacia, Eucalyptus, Larix, Picea, Pinus and Populus although the focal point of this review will include only the genus Pinus. The most important forest tree hybrids in this genera include the inter-specific Pinus hybrids in USA, Korea and Australia. Of those hybrids that are used commercially, by far the most common are first generation crosses. In particular, these hybrids appear to be most successful when they are planted in areas outside the normal plantation zones of at least one of the parent species. Generalisations about genotype×environment interactions across genera were not found, and interactions seemed to be specific to the hybrid concerned. Published estimates of hybrid genetic parameters were not common, but the following general trends were found: (i) heritabilities calculated from hybrid populations were usually larger when compared to pure species estimates; (ii) dominance variance varied with taxon, trait and age; (iii) epistatic variance, although only estimated in one case, was negligible when compared with the additive and dominance effects. It is possible that inflated heritability estimates were obtained because the infinitesimal model may not be appropriate in hybrid populations. Other alternative models should be investigated in the future. The ability to reliably predict hybrid progeny performance from general combining abilities of pure species populations depended on trait and hybrid, although it appeared that this ratio was greater for traits of higher heritability. No consistent evidence was found to support the hypothesis that hybrids may be more adaptable across environments due to their greater heterozygosity and therefore their ability to buffer different environmental stresses. Although there are still gaps in our knowledge of how hybrids behave, some hybrid combinations are without doubt highly successful, and the impact of the use of hybrids in commercial forestry should not be underestimated.

Y chromosome polymorphism is a strong determinant of male fitness in Drosophila melanogaster.

In many species, the Y (or W) chromosome carries relatively few functional genes. This observation motivates the null hypothesis that the Y will be a minor contributor to genetic variation for fitness. Previous data and theory supported the null hypothesis, but evidence presented here shows that the Y of Drosophila melanogaster is a major determinant of a male's total fitness, with standing genetic variation estimated to be 68% of that of an entire X/autosome genomic haplotype. Most Y-linked genes are expressed during spermatogenesis, and correspondingly, we found that the Y influences fitness primarily through its effect on a male's reproductive success (sperm competition and/or mating success) rather than his egg-to-adult viability. But the fitness of a Y highly depended on the genetic makeup of its bearer, reverting from high to low in different genetic backgrounds. This pattern leads to large epistatic (inconsistent among backgrounds) but no additive (consistent among backgrounds) Y-linked genetic variance for fitness. On a microevolutionary scale, the observed large epistatic variation on the Y substantially reduces heritable variation for fitness among males, and on a macroevolutionary scale, the Y produces strong selection for genomic rearrangements that move interacting genes onto the nonrecombining region of the Y.

The contrasting genetic architecture of wing size and shape in Drosophila melanogaster.

Surprisingly little is known about the genetic architecture of body size in natural populations of Drosophila melanogaster. Using both generation means and triple-test-cross analyses, we investigated the genetic architecture of wing size (an indicator of body size) and wing shape in a naturally occurring body size cline. For wing size, we found significant epistatic genetic variance and evidence of past directional selection for increased body size. While wing shape also exhibits significant epistatic genetic variance, there was no indication of directional selection, suggesting instead a history of optimizing selection. Our results support the idea that epistatic variance may be more common in natural populations than was once suspected. Also, our results suggest substantial directional selection on wing size but not shape.