POLYGENIC MUTATION IN DROSOPHILA MELANOGASTER: ESTIMATES FROM DIVERGENCE AMONG INBRED STRAINS

A highly inbred line of Drosophila melanogaster was subdivided into 25 replicate sublines, which were independently maintained for 100 generations with 10 pairs of unselected flies per generation. The polygenic mutation rate (V_M) for two quantitative traits, abdominal and sternopleural bristle number, was estimated from divergence among sublines at 10 generation intervals from generations 30-100, and from response of each line to divergent selection after more than 65 generations of mutation accumulation. Estimates of V_M averaged over males and females both from divergence among lines and from response to selection within lines were 3.3 × 10^-3 V_E for abdominal bristles and 1.5 × 10^-3 V_E for sternopleural bristles, where V_E is the environmental variance. The actual rate of production of mutations affecting these traits may be considerably higher if the traits are under stabilizing selection, and if mutations affecting bristle number have deleterious effects on fitness. There was a substantial component of variance for sex × mutant effect interaction and the sublines evolved highly significant mutational variation in sex dimorphism of abdominal bristle number. Pleiotropic effects on sex dimorphism may be a general property of mutations at loci determining bristle number.     

High Resolution Mapping of Genetic Factors Affecting Abdominal Bristle Number in Drosophila Melanogaster

Factors responsible for selection response for abdominal bristle number and correlated responses in sternopleural bristle number were mapped to the X and third chromosome of Drosophila melanogaster. Lines divergent for high and low abdominal bristle number were created by 25 generations of artificial selection from a large base population, with an intensity of 25 individuals of each sex selected from 100 individuals of each sex scored per generation. Isogenic chromosome substitution lines in which the high (H) X or third chromosome were placed in an isogenic low (L) background were derived from the selection lines and from the 93 recombinant isogenic (RI) HL X and 67 RI chromosome 3 lines constructed from them. Highly polymorphic neutral r00 transposable elements were hybridized in situ to the polytene chromosomes of the RI lines to create a set of cytogenetic markers. These techniques yielded a dense map with an average spacing of 4 cM between informative markers. Factors affecting bristle number, and relative viability of the chromosome 3 RI lines, were mapped using a multiple regression interval mapping approach, conditioning on all markers >/=10 cM from the tested interval. Two factors with large effects on abdominal bristle number were mapped on the X chromosome and five factors on the third chromosome. One factor with a large effect on sternopleural bristle number was mapped to the X and two were mapped to the third chromosome; all factors with sternopleural effects corresponded to those with effects on abdominal bristle number. Two of the chromosome 3 factors with large effects on abdominal bristle number were also associated with reduced viability. Significant sex-specific effects and epistatic interactions between mapped factors of the same order of magnitude as the additive effects were observed. All factors mapped to the approximate positions of likely candidate loci (ASC, bb, emc, h, mab, Dl and E(spl)), previously characterized by mutations with large effects on bristle number.     

Polygenic Mutation in Drosophila Melanogaster: The Causal Relationship of Bristle Number to Fitness

The association between sternopleural and abdominal bristle number and fitness in Drosophila melanogaster was determined for sublines of an initially highly inbred strain that were maintained by divergent artificial selection for 150 generations or by random mating for 180 generations. Replicate selection lines had more extreme bristle numbers than those that were maintained without artificial selection at the same census size for approximately the same number of generations. The average fitness, estimated by a single generation of competition against a compound autosome strain, was 0.17 for lines selected for high and low abdominal bristle numbers and 0.19 for lines selected for high and low sternopleural bristle number. The average fitness of unselected lines, 0.46, was significantly higher than that of the selection lines. The fitnesses and the relationships of bristle number to fitness in progeny of all possible crosses of high X high (H X H), high X low (H X L) and low X low (L X L) selection lines were examined to determine whether the observed intermediate optima were caused by direct stabilizing selection on bristle number or by apparent stabilizing selection mediated through deleterious pleiotropic fitness effects of mutations affecting bristle number. Although bristle number was nearly additive for progeny of H X H, H X L and L X L crosses among sternopleural bristle selection lines, their mean fitnesses were not significantly different from each other, or from the mean fitness of the unselected lines, suggesting partly or completely recessive pleiotropic fitness effects cause apparent stabilizing selection. The average fitness of the progeny of H X H abdominal bristle selection lines was not significantly different from the fitness of unselected lines, but the mean fitness of the progeny of L X L crosses was not significantly different from that of the pure low lines. This is consistent with direct selection against low but not high abdominal bristle number, but the interpretation is confounded by variation in average degree of dominance for fitness (on average recessive in the high abdominal bristle selection lines and additive in the low abdominal bristle selection lines). Neither direct stabilizing selection nor pleiotropy, therefore, can account for all the observations.     

Polygenic Mutation in Drosophila Melanogaster: Genetic Analysis of Selection Lines

We have conducted genetic analyses of 12 long-term selection lines of Drosophila melanogaster derived from a highly inbred base population, containing new mutations affecting abdominal and sternopleural bristle number. Biometric analysis of the number of effective factors differentiating the selected lines from the base inbred indicated that with the exception of the three lines selected for increased number of abdominal bristles, three or more mutations contributed to the responses of the selection lines. Analysis of the chromosomal distribution of effects revealed that mutations affecting abdominal bristle number occurred on all three major chromosomes. In addition, Y-linked mutations with effects ranging from one to three bristles occurred in all three lines selected for decreased number of abdominal bristles, as well as in one line selected for increased abdominal bristle number. Mutations affecting sternopleural bristle number were mainly on the X and third chromosomes. One abdominal and one sternopleural selection line showed evidence of a segregating lethal with large effects on bristle number. As an indirect test for allelism of mutations occurring in different selection lines, the three lines selected in the same direction for the same trait were crossed in all possible combinations, and selection continued from the F(2) hybrids. Responses of the hybrid lines usually did not exceed those of the most extreme parental lines, indicating that the responses of the parental lines may have been partly due to mutations at the same loci, although other interpretations are possible.     

The Response to Artificial Selection from New Mutations in Drosophila Melanogaster

Twenty generations of divergent selection for abdominal bristle number were carried out starting from a completely homozygous population of Drosophila melanogaster. All lines were selected with the same proportion (20%) but at two different numbers of selected parents of each sex (5 or 25). A significant response to selection was detected in eight lines (out of 40) and, in most cases, it could be wholly attributed to a single mutation of relatively large effect (0.5-2 phenotypic standard deviations). The ratio of new mutational variance to environmental variance was estimated to be (0.33 +/- 0.11) X 10(-3). The distribution of mutant effects was asymmetrical, both with respect to bristle number (85% of it was negative) and to fitness (most detected bristle mutations were lethal or semilethal). Moreover, this distribution was leptokurtic, due to the presence of major genes. Gene action on bristles ranged from additive to completely recessive, no epistatic interactions being found. In agreement with theory, larger responses in each direction were achieved by those lines selected at greater effective population sizes. Furthermore, the observed divergence between lines selected in opposite directions was proportional to their effective size, as predicted for mutations of large effect.     

Polygenic Mutation in Drosophila Melanogaster: Non-Linear Divergence among Unselected Strains

A highly inbred strain of Drosophila melanogaster was subdivided into 20 replicate sublines that were maintained independently with 10 pairs of randomly sampled parents per generation for 180 generations. The variance between lines in abdominal and sternopleural bristle number increased little after 100 generations, in contrast to the neutral expectation of a linear increase; and the covariances of line means between different generations declined with increasing number of generations apart, in contrast to the neutral expectation of constant covariance. Thus, under a neutral model, the estimates of mutational variance were lower than for previous estimates from the first 100 generations of subline divergence. An autoregressive model was fitted to the variance of line means that indicated strong natural selection. There is no single unequivocal explanation for the results. Possible and nonexclusive alternatives include stabilizing selection on bristle number and deleterious effects on fitness of bristle mutations. The inferred strengths of selection on both traits are too high for stabilizing selection alone, and the between-line variance did not continue to increase sufficiently for pleiotropy alone to account for the observations. A third potential explanation that does not invoke selection is duplicate epistasis between mutations affecting bristle number.     

Temporal uniformity of the spontaneous mutational variance of quantitative traits in Drosophila melanogaster

Spontaneous mutations were allowed to accumulate over 209 generations in more than 100 lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and subsequently maintained under strong inbreeding (equivalent to full-sib mating). Traits scored were: abdominal (AB) and sternopleural (ST) bristle number, wing length (WL) and egg-to-adult viability (V). On two occasions--early (generations 93-122) and late (generations 169-209)--ANOVA estimates of the mutational variance and the mutational line x generation interaction variance were obtained. Mutational heritabilities of morphological traits ranged from 2 x 10(-4) to 2 x 10(-3) and the mutational coefficient of variation of viability was 0.01. For AB, WL and V, temporal uniformity of the mutational variance was observed. However, a fluctuation of the mutational heritability of ST was detected and could be ascribed to random genotype x environment interaction.     

Condition dependence and the nature of genetic variation for male sex comb bristle number in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Genetic architecture of variation underlying male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila, was examined. First, in order to test for condition dependence, diet was manipulated in a set of ten Drosophila melanogaster full-sib families. We confirmed heightened condition dependent expression of sex comb bristle number and its female homologue (distal transverse row bristles) as compared to non-sex sternopleural bristles. Significant genotype by environment effects were detected for the sex traits indicating a genetic basis for condition dependence. Next we measured sex comb bristle number and sternopleural bristle number, as well as residual mass, a commonly used condition index, in a set of thirty half-sib families. Sire effect was not significant for sex comb and sternopleural bristle number, and we detected a strong dominance and/or maternal effect or X chromosome effect for both traits. A strong sire effect was detected for condition and its heritability was the highest as compared to sex comb and sternopleural bristles. We discuss our results in light of the rapid response to divergent artificial selection for sex comb bristle number reported previously. The nature of genetic variation for male sex traits continues to be an important unresolved issue in evolutionary biology.     

Effect of stressful and nonstressful growth temperatures on variation of sternopleural bristle number in Drosophila melanogaster

The effect of stressful (31 degrees C) and nonstressful (25 degrees C) growth temperatures on quantitative variation and developmental stability (fluctuating asymmetry) of Drosophila melanogaster was examined in a short-term selection experiment on sternopleural bristle number. Realized heritabilities based on 10 generations of selection in an upward direction did not differ between the two temperature regimes, which indicated that additive genetic variation was not affected by a high, stressful temperature. Phenotypic variability and fluctuating asymmetry of sternopleural bristles were significantly higher under stressful conditions when averaged over generations, although most pairwise comparisons in separate generations showed nonsignificant differences between temperatures.     

Polygenic mutation in Drosophila melanogaster: Mapping spontaneous mutations affecting sensory bristle number

Our ability to predict long-term responses to artificial and natural selection, and understand the mechanisms by which naturally occurring variation for quantitative traits is maintained, depends on detailed knowledge of the properties of spontaneous polygenic mutations, including the quantitative trait loci (QTL) at which mutations occur, mutation rates, and mutational effects. These parameters can be estimated by mapping QTL that cause divergence between mutation-accumulation lines that have been established from an inbred base population and selected for high and low trait values. Here, we have utilized quantitative complementation to deficiencies to map QTL at which spontaneous mutations affecting Drosophila abdominal and sternopleural bristle number have occurred in 11 replicate lines during 206 generations of divergent selection. Estimates of the numbers of mutations were consistent with diploid per-character mutation rates for bristle traits of 0.03. The ratio of the per-character mutation rate to total mutation rate (0.023) implies that >2% of the genome could affect just one bristle trait and that there must be extensive pleiotropy for quantitative phenotypes. The estimated mutational effects were not, however, additive and exhibited dependency on genetic background consistent with diminishing epistasis. However, these inferences must be tempered by the potential for epistatic interactions between spontaneous mutations and QTL affecting bristle number on the deficiency-bearing chromosomes, which could lead to overestimates in numbers of QTL and inaccurate inference of gene action.     

Drosophila bristles and the nature of quantitative genetic variation

Numbers of Drosophila sensory bristles present an ideal model system to elucidate the genetic basis of variation for quantitative traits. Here, we review recent evidence that the genetic architecture of variation for bristle numbers is surprisingly complex. A substantial fraction of the Drosophila genome affects bristle number, indicating pervasive pleiotropy of genes that affect quantitative traits. Further, a large number of loci, often with sex- and environment-specific effects that are also conditional on background genotype, affect natural variation in bristle number. Despite this complexity, an understanding of the molecular basis of natural variation in bristle number is emerging from linkage disequilibrium mapping studies of individual candidate genes that affect the development of sensory bristles. We show that there is naturally segregating genetic variance for environmental plasticity of abdominal and sternopleural bristle number. For abdominal bristle number this variance can be attributed in part to an abnormal abdomen-like phenotype that resembles the phenotype of mutants defective in catecholamine biosynthesis. Dopa decarboxylase (Ddc) encodes the enzyme that catalyses the final step in the synthesis of dopamine, a major Drosophila catecholamine and neurotransmitter. We found that molecular polymorphisms at Ddc are indeed associated with variation in environmental plasticity of abdominal bristle number.     

Hybrid Dysgenesis-Induced Quantitative Variation on the X Chromosome of Drosophila Melanogaster

To determine the ability of the P-M hybrid dysgenesis system of Drosophila melanogaster to generate mutations affecting quantitative traits, X chromosome lines were constructed in which replicates of isogenic M and P strain X chromosomes were exposed to a dysgenic cross, a nondysgenic cross, or a control cross, and recovered in common autosomal backgrounds. Mutational heritabilities of abdominal and sternopleural bristle score were in general exceptionally high-of the same magnitude as heritabilities of these traits in natural populations. P strain chromosomes were eight times more mutable than M strain chromosomes, and dysgenic crosses three times more effective than nondysgenic crosses in inducing polygenic variation. However, mutational heritabilities of the bristle traits were appreciable for P strain chromosomes passed through one nondysgenic cross, and for M strain chromosomes backcrossed for seven generations to inbred P strain females, a result consistent with previous observations on mutations affecting quantitative traits arising from nondysgenic crosses. The new variation resulting from one generation of mutagenesis was caused by a few lines with large effects on bristle score, and all mutations reduced bristle number.     

The isolation of polygenic factors controlling bristle score in Drosophila melanogaster. I. Allocation of third chromosome sternopleural bristle effects to chromosome sections

A single third chromosome C, with a high sternopleural bristle score, had been extracted from an artificial selection line. C was divided into five chromosomal sections by recombination with a multiply marked third chromosome ruseca, which had a low sternopleural bristle score. A nonuniform distribution of sternopleural bristle effect with physical length of chromosome was observed. The second section (26-44 cM) of C carried the most sternopleural bristle effect (10 bristles when homozygous), the first (0-26 cM) and third (44-62 cM) also carried significant sternopleural bristle effects (six and five bristles, respectively). The fourth section (62-71 cM) carried a small but significant effect (less than one bristle) while the fifth section (71-101 cM) carried little effect when alone (less than one bristle), though it did carry effects which had an epistatic interaction with those of the first and second sections.     

Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster

A restriction enzyme survey of a 110-kb region including the achaete scute complex (ASC) examined 14 polymorphic molecular markers in a sample of 56 naturally occurring chromosomes. Large insertions as a class were associated with a reduction in both sternopleural and abdominal bristle number, supporting deleterious mutation-selection equilibrium models for the maintenance of quantitative genetic variation. Two polymorphic sites were independently associated with variation in bristle number measured in two genetic backgrounds as assessed by a permutation test. A 6-bp deletion near sc alpha is associated with sternopleural bristle number variation in both sexes and a 3.4-kb insertion between sc beta and sc gamma is associated with abdominal bristle number variation in females. Under an additive genetic model, the small deletion polymorphism near sc alpha accounts for 25% of the total X chromosome genetic variation in sternopleural bristle number, and the 3.4 kb insertion accounts for 22% of the total X chromosome variation in female abdominal bristle number. The observation of common polymorphisms associated with variation in bristle number is more parsimoniously explained by models that incorporate balancing selection or assume variants affecting bristle number are neutral, than mutation-selection equilibrium models.     

High-resolution mapping of quantitative trait loci for sternopleural bristle number in Drosophila melanogaster.

We have mapped quantitative trait loci (QTL) harboring naturally occurring allelic variation for Drosophila bristle number. Lines with high (H) and low (L) sternopleural bristle number were derived by artificial selection from a large base population. Isogenic H and L sublines were extracted from the selection lines, and populations of X and third chromosome H/L recombinant isogenic lines were constructed in the homozygous low line background. The polymorphic cytological locations of roo transposable elements provided a dense molecular marker map with an average intermarker distance of 4.5 cM. Two X chromosome and six chromosome 3 QTL affecting response to selection for sternopleural bristle number and three X chromosome and three chromosome 3 QTL affecting correlated response in abdominal bristle number were detected using a composite interval mapping method. The average effects of bristle number QTL were moderately large, and some had sex-specific effects. Epistasis between QTL affecting sternopleural bristle number was common, and interaction effects were large. Many of the intervals containing bristle number QTL coincided with those mapped in previous studies. However, resolution of bristle number QTL to the level of genetic loci is not trivial, because the genomic regions containing bristle number QTL often did not contain obvious candidate loci, and results of quantitative complementation tests to mutations at candidate loci affecting adult bristle number were ambiguous.     

Variation and evolution of male sex combs in Drosophila: nature of selection response and theories of genetic variation for sexual traits

We investigated the genetic architecture of variation in male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila. Twenty-four generations of divergent artificial selection for sex comb bristle number in a heterogeneous population of Drosophila melanogaster resulted in a significant response that was more pronounced in the direction of low bristle numbers. We observed a strong positive correlated response to selection in the corresponding female transverse bristle row. The correlated response in male abdominal and sternopleural bristle numbers, on the other hand, did not follow the same pattern as sex comb bristle number differences between selection lines. Relaxation-of-selection experiments along with mate choice and fecundity assays using the selection lines developed demonstrated the action of stabilizing selection on sex comb bristle number. Our results show (1) substantial genetic variation underlying sex comb bristle number variation; (2) a weak relationship between the sex comb and developmentally related, non-sex bristle systems; and (3) that sexual selection may be a driving force in sex comb evolution, indicating the potential of sex combs to diversify rapidly during population differentiation and speciation. We discuss the implications of these results for theories of genetic variation in display and nondisplay male sex traits.     

Studies on the Scutellar Bristles of DROSOPHILA MELANOGASTER. II. Long-Term Selection for High Bristle Number in the Oregon Rc Strain and Correlated Responses in Abdominal Chaetae

Results are presented of 135 generations of selection for high scutellar bristle number in two lines M and M3 derived from the same original mating of one female with 5 bristles by one male with 4 bristles, the latter being the wild-type canalised phenotype. Results are also given of two relaxed lines per line and of a reselection line M2 derived from the first relaxed line of line M which had regressed almost to base population level. The effect of introducing the sc(1) allele into the M and M3 selected backgrounds was studied at generations 39-44. At the end of selection the effect of an extra dose of sc(+) was also studied in males of all selected backgrounds. The correlated responses in abdominal bristles were followed in all lines.-Considering their common origin, the selection lines differed markedly in pattern of scutellar response and in most other aspects observed, namely correlated responses in abdominals and p.c. scutellars, sex differences, and behaviour on relaxation. Selection limits for scutellar bristles in lines M and M2 were equal to or greater than the most extreme reported in the literature.-The probit span of the canalised 4 bristle class decreased in each selection line as the mean scutellar bristle number increased, and increased again in the relaxed lines as the mean bristle number decreased. In the context of an hypothesis that canalisation at 4 bristle is due to regulation of the scute locus, this result is now interpreted as being due mainly to selection for poor regulators of sc(+), in contrast to a previous interpretation that only the minor gene background was altered by selection, the canalisation (regulation) genotype not being affected.-Introducing the sc(1) allele into the selected backgrounds M and M3 showed a reduced effect on sc(1) flies compared with sc(+) flies, and an interaction of sc(1) and sc(+) with selected background. sc(1) flies had about the same number of bristles in both backgrounds though the mean of sc(+) flies in line M was about 3sigma higher than in line M3. Dominance of sc(+) to sc(1) was reduced slightly in M3. However, the effect of an extra dose of sc(+) at the end of selection was about the same as in unselected in all lines, so the first or dominance level of regulation of the scute locus was not significantly affected by selection, though the second or canalisation level of regulation was.-A large positive correlated response in abdominal bristles occurred in all lines. The response in line M was about twice that in M2 and M3 and was in fact as large as can be obtained from direct selection on abdominals. In line M some genes may have been selected with a proportionately greater effect on abdominals than on scutellars. This is supported by the further observation in line M that the abdominal scores of flies with particular scutellar bristles scores increased as the scutellar mean increased. An attempt was made to apply to these results Rendel's (1962) model of competition between scutellars and abdominals for common bristle-making resources. This could not be done satisfactorily mainly because the assumptions in the model about the similarity of effects in scute and wild-type flies were not met in the present material.     

Variation in Drosophila sensory bristle number at 'Evolution Canyon'

'Evolution Canyon' on Mount Carmel, Israel, displays highly contrasting physical and biotic environments on a micro-geographic scale, and is a natural laboratory for investigating genetic responses to variable and extreme environments across species. Samples of Drosophila melanogaster and D. simulans were collected from three sites each on the north- and south-facing slopes of the canyon along altitudinal transects, and one site on the valley floor. Numbers of abdominal and sternopleural sensory bristles were recorded for each of these subpopulations in three thermal environments. In D. simulans, sternopleural bristle number exhibited micro-geographic differentiation between the north- and south-facing slopes, while abdominal bristle number was stable across subpopulations. In D. melanogaster, the magnitudes of the difference in mean sternopleural bristle number between the north- and south-facing slopes and of mean abdominal bristle number along the altitudinal gradients were both conditional on rearing temperature. Thus, the pattern of genetic variation between sites was consistent with underlying heterogeneity of genetic mechanisms for response to the same environmental gradients between traits and sibling species. In contrast, the genetic architecture of bristle number at the level of variation within populations was very similar between species for the same bristle trait, although the two traits differed in the relative contribution of genotype by temperature and genotype by sex interaction.     

The genetic architecture of selection response. Inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster.

Quantitative trait loci (QTL) affecting responses and correlated responses to selection for abdominal and sternopleural bristle number have been mapped with high resolution to the X and third chromosomes. Advanced intercross recombinant isogenic chromosomes were constructed from high and low selection lines in an unselected inbred background, and QTL were detected using composite interval mapping and high density transposable element marker maps. We mapped a total of 26 bristle number QTL with large effects, which were in or immediately adjacent to intervals previously inferred to contain bristle number QTL on these chromosomes. The QTL contributing to response to selection for high bristle number were not the same as those contributing to response to selection for low bristle number, suggesting that distributions of allelic effects per locus may be asymmetrical. Correlated responses were more often attributable to loose linkage than pleiotropy or close linkage. Bristle number QTL mapping to the same locations have been inferred in studies with different parental strains. Of the 26 QTL, 20 mapped to locations consistent with candidate genes affecting peripheral nervous system development and/or bristle number. This facilitates determining the molecular basis of quantitative variation and allele frequencies by associating molecular variation at the candidate genes with phenotypic variation in bristle number in samples of alleles from nature.     

Transposable Element-Induced Response to Artificial Selection in DROSOPHILA MELANOGASTER

The P family of transposable elements in Drosophila melanogaster transpose with exceptionally high frequency when males from P strains carrying multiple copies of these elements are crossed to females from M strains that lack P elements, but with substantially lower frequency in the reciprocal cross. Transposition is associated with enhanced mutation rates, caused by insertion and deletion of P elements, and chromosome rearrangements. If P element mutagenesis creates additional variation for quantitative traits, accelerated response to artificial selection of progeny of M female female X P male male strain crosses is expected, compared with that from progeny of P female female X M male male strain crosses.--Divergent artificial selection for number of bristles on the last abdominal tergite was carried out for 16 generations among the progeny of P-strain males (Harwich) and M-strain females (Canton-S) and also of M-strain males (Canton-S) and P-strain females (Harwich). Each cross was replicated four times. Average realized heritability of abdominal bristle score for the crosses in which P transposition was expected was 0.244 +/- 0.017, 1.5 times greater than average heritability estimated from crosses in which transposition was expected to be rare (0.163 +/- 0.010). Phenotypic variance of abdominal bristle score increased by a factor of four in lines selected from M female female X P male male crosses when compared with those selected from P female female X M male male hybrids. Not all quantitative genetic variation induced by P elements is additive. A substantial fraction of nonadditive genetic variation is implicated by chromosomal analysis, which demonstrates deleterious fitness effects of the mutations when homozygous.--Several putative "quantitative" mutations were identified from chromosomes extracted from the selected lines; these will form the basis for further investigation at the molecular level of the genes controlling quantitative inheritance.