The Effects of Fatigue and the Post-Concussion Syndrome on Executive Functioning in Traumatic Brain Injury and Healthy Comparisons

In this study; behavioural manifestations of compromised executive control; including perseveration and reduced inductive reasoning; on the Wisconsin Card Sorting Test (WCST) were investigated. Performance was affected by fatigue in both a head-injured and matched population; which has implications for health care professionals involved in rehabilitation and assessment. A fatigue condition was manipulated for 15 moderate to severe traumatic brain injury (TBI) individuals through the course of a three-hour neuropsychological testing session. A comparison sample of 15 participants in a group of 'no history of TBI' was fatigued through the same approach. All fatigued participants (with and without TBI) displayed trends towards increased levels of perseveration and reduced inductive reasoning on the WCST. Thus; the effects of fatigue on high-level functioning are pervasive even when not head-injured. This finding supports the sub-optimal performance in cognitive skills; specifically in executive control; that is often found in fatigued people. These findings are relevant for the manner in which rehabilitation interventions and medico-legal assessments are structured. Importantly; the order of tests; their interpretation and rest sessions should be clearly indicated and interpreted in assessment reports and rehabilitation sessions

The genetic architecture of fitness in a seed beetle: assessing the potential for indirect genetic benefits of female choice.

BACKGROUND: Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity). RESULTS: We used the bio model to estimate six components of genetic and environmental variance in fitness. We found sizeable additive and non-additive genetic variance in F1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. CONCLUSION: Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should be inclusive and should include quantifications of offspring reproductive success. We note that our estimate of additive genetic variance in F1 productivity (CVA=14%) is sufficient to generate indirect selection on female choice. However, our results also show that the major determinant of offspring fitness is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis) for F1 productivity. We discuss the processes that may maintain additive and non-additive genetic variance for fitness and how these relate to indirect selection for female choice.

Quantifying the Effects of Lance Nematode Parasitism in Creeping Bentgrass.

We compared photosynthesis and multispectral radiometry (MSR) measurements with visual quality ratings for assessment of feeding injury to creeping bentgrass caused by the lance nematode (Hoplolaimus galeatus) using artificially infested microplots and a naturally infested putting green. Nematode feeding resulted in negative visual and MSR effects on creeping bentgrass in microplots. Visual quality ratings were correlated more consistently with nematode densities than either individual MSR variables or factor models of MSR variables. Threshold estimates for H. galeatus population densities associated with unacceptable bentgrass quality in microplots varied widely by month and year. Similarly, the relationship between H. galeatus population density and turf health indicators (including MSR measurements, visual ratings, and net photosynthetic rate) varied with cultivar and management practice (irrigation frequency and mowing height) in the naturally infested putting green. Notably, negative effects of nematode feeding were not consistently associated with more stressful management practices, suggesting that stress avoidance is not a reliable deterrent to H. galeatus damage in creeping bentgrass. Damage thresholds for this nematode-host association are dynamic and should be used with caution.

Population Dynamics of the Lance Nematode (Hoplolaimus galeatus) in Creeping Bentgrass.

The effects of management practices and nematode population density on the seasonal fluctuationsin lance nematode (Hoplolaimus galeatus) populations in creeping bentgrass were studiedin a naturally infested experimental putting green and in artificially infested microplots. In general, H. galeatus populations increased from late spring through midsummer, declined in August, and increased again in the fall. Population increase in microplots was strongly density dependent, with final population densities inversely proportional to inoculum levels. Ectoparasitic populationsof H. galeatus in both studies were composed of adults and juveniles, whereas endoparasiticpopulations were almost exclusively juveniles. H. galeatus populations in the naturallyinfested site were aggregated spatially, but the aggregation was not temporally stable. Nematodepopulations were not affected by bentgrass cultivar selection or irrigation frequency.

Heritability, correlations and in silico mapping of locomotor behavior and neurochemistry in inbred strains of mice.

The midbrain dopamine system mediates normal and pathologic behaviors related to motor activity, attention, motivation/reward and cognition. These are complex, quantitative traits whose variation among individuals is modulated by genetic, epigenetic and environmental factors. Conventional genetic methods have identified several genes important to this system, but the majority of factors contributing to the variation remain unknown. To understand these genetic and environmental factors, we initiated a study measuring 21 behavioral and neurochemical traits in 15 common inbred mouse strains. We report trait data, heritabilities and genetic and non-genetic correlations between pheno-types. In general, the behavioral traits were more heritable than neurochemical traits, and both genetic and non-genetic correlations within these trait sets were high. Surprisingly, there were few significant correlations between the behavioral and the individual neurochemical traits. However, striatal serotonin and one measure of dopamine turnover (DOPAC/DA) were highly correlated with most behavioral measures. The variable accounting for the most variation in behavior was mouse strain and not a specific neurochemical measure, suggesting that additional genetic factors remain to be determined to account for these behavioral differences. We also report the prospective use of the in silico method of quantitative trait loci (QTL) analysis and demonstrate difficulties in the use of this method, which failed to detect significant QTLs for the majority of these traits. These data serve as a framework for further studies of correlations between different midbrain dopamine traits and as a guide for experimental cross designs to identify QTLs and genes that contribute to these traits.

Genetic Diversity and Aggressiveness of Ophiosphaerella korrae, a Cause of Spring Dead Spot of Bermudagrass.

The distribution of three Ophiosphaerella spp. that cause spring dead spot (SDS) of bermudagrass was studied by sampling at 24 locations in the southeastern United States. O. korrae was isolated from 73% of the 204 bermudagrass cores collected and was the only SDS pathogen recovered at most sites. O. herpotricha was isolated at three locations in Kentucky and one in North Carolina, and O. narmari was found at two locations in North Carolina. Most O. korrae isolates collected from Alabama, Kentucky, Mississippi, Tennessee, and Virginia clustered in an amplified fragment length polymorphism group (AFLP group II) that was distinct from Kentucky bluegrass isolates collected throughout North America and similar to bermudagrass isolates from Kansas and Oklahoma (AFLP group I). A third AFLP group (III) consisting of bermudagrass isolates from Mississippi and Virginia was identified. Isolates representing AFLP groups II and III grew more rapidly on potato dextrose agar at 25 and 30°C than those in group I. O. korrae isolates differed in their aggressiveness to two bermudagrass cultivars in greenhouse studies, but these differences were not associated with AFLP group, location, or host from which the isolate was collected.

Environment-dependent reversal of a life history trade-off in the seed beetle Callosobruchus maculatus.

Environmental manipulations have consistently demonstrated a cost of reproduction in the capital-breeding seed beetle, Callosobruchus maculatus, as females deprived of seeds or mates lay fewer eggs and thereby increase their longevity. Yet fecundity and longevity tend to be positively correlated within populations, perhaps as a consequence of individual differences in resource acquisition. We conducted a split-brood experiment that combined a manipulation of seed availability (seeds present or absent) with a quantitative-genetic analysis of fecundity and lifespan in each environment. Each trait was significantly heritable in each environment. Seed availability not only altered mean fecundity and longevity between environments, but also modified how the traits were correlated within environments. The signs of both the phenotypic and genetic correlations switched from positive when seeds were present to negative when seeds were absent. This reversal persisted even after the effect of body mass (a potential indicator of resource acquisition) was statistically controlled. Cross-environment genetic correlations were positive but significantly less than one for each trait. We suggest that the reversal of the fecundity-longevity relationship depends on a shift in the relative importance of resource-acquisition and resource-allocation loci between environments. In particular, a cost of reproduction may be apparent at the individual level only when seeds are scarce or absent because differences in reproductive effort become large enough to overwhelm differences in resource acquisition. Despite their common dependence on resources acquired during larval stages, fecundity and lifespan in C. maculatus do not appear to be tightly coupled in a physiological or genetic sense.

Rapid mutational declines of viability in Drosophila.

High rates of mildly deleterious mutation could cause the extinction of small populations, reduce neutral genetic variation and provide an evolutionary advantage for sex. In the first attempts to estimate the rate of mildly deleterious mutation, Mukai and Ohnishi allowed spontaneous mutations to accumulate on D. melanogaster second chromosomes shielded from recombination and selection. Viability of the shielded chromosomes appeared to decline rapidly, implying a deleterious mutation rate on the order of one per zygote per generation. These results have been challenged, however; at issue is whether Mukai and Ohnishi may have confounded viability declines caused by mutation with declines resulting from environmental changes or other extraneous factors. Here, using a method not sensitive to non-mutational viability changes, I reanalyse the previous mutation-accumulation (MA) experiments, and report the results of a new one. I show that in each of four experiments, including Mukai's two experiments, viability declines due to mildly deleterious mutations were rapid. The results give no support for the view that Mukai overestimated the declines. Although there is substantial variation in estimates of genomic mutation rates from the experiments, this variation is probably due to some combination of sampling error, strain differences and differences in assay conditions, rather than to failure to distinguish mutational and non-mutational viability changes.

Development of Brown Patch and Pythium Blight in Tall Fescue as Affected by Irrigation Frequency, Clipping Removal, and Fungicide Application.

We studied the effects of irrigation frequency, clipping removal, and fungicide application on the development of Rhizoctonia brown patch (Rhizoctonia solani) and Pythium blight (Pythium aphanidermatum) in tall fescue. Brown patch severity was not significantly different between plots irrigated daily and those irrigated on alternate days. Similarly, no differences in brown patch were observed in plots where grass clippings were returned to the sward with a mulching mower compared with plots where clippings were removed. Preventive applications of azox-ystrobin at 35-day intervals or postinfection applications of chlorothalonil reduced brown patch severity, but only the azoxystrobin treatment provided aesthetically acceptable (<10%) levels of brown patch control. However, azoxystrobin applications also increased Pythium blight compared with untreated or chlorothalonil-treated tall fescue, especially in plots that received daily irrigation.

New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster.

The genomic rate and distribution of effects of deleterious mutations are important parameters in evolutionary theory. The most detailed information comes from the work of Mukai and Ohnishi, who allowed mutations to accumulate on Drosophila melanogaster second chromosomes, shielded from selection and recombination by being maintained heterozygous in males. Averaged over studies, the estimated rate of nonlethal viability mutations per second chromosome per generation under an equal-effects model, UBM, was 0. 12, suggesting a high genomic mutation rate. We have performed a mutation-accumulation experiment similar to those of Mukai and Ohnishi, except that three large homozygous control populations were maintained. Egg-to-adult viability of 72 nonlethal mutation-accumulation (MA) lines and the controls was assayed after 27-33 generations of mutation accumulation. The rate of decline in mean viability was significantly lower than observed by Mukai, and the rate of increase in among-line variance was significantly higher. Our UBM estimate of 0.02 is much lower than the previous estimates. Our results suggest that the rate of mutations that detectably reduce viability may not be much greater than the lethal mutation rate (0.01 in these lines), but the results also are consistent with models that include many mutations with very small effects.

Genotype-environment interaction at quantitative trait loci affecting sensory bristle number in Drosophila melanogaster.

The magnitude of segregating variation for bristle number in Drosophila melanogaster exceeds that predicted from models of mutation-selection balance. To evaluate the hypothesis that genotype-environment interaction (GEI) maintains variation for bristle number in nature, we quantified the extent of GEI for abdominal and sternopleural bristles among 98 recombinant inbred lines, derived from two homozygous laboratory strains, in three temperature environments. There was considerable GEI for both bristle traits, which was mainly attributable to changes in rank order of line means. We conducted a genome-wide screen for quantitative trait loci (QTLs) affecting bristle number in each sex and temperature environment, using a dense (3.2-cM) marker map of polymorphic insertion sites of roo transposable elements. Nine sternopleural and 11 abdominal bristle number QTLs were detected. Significant GEI was exhibited by 14 QTLs, but there was heterogeneity among QTLs in their sensitivity to thermal and sexual environments. To further evaluate the hypothesis that GEI maintains variation for bristle number, we require estimates of allelic effects across environments at genetic loci affecting the traits. This level of resolution may be achievable for Drosophila bristle number because candidate loci affecting bristle development often map to the same location as bristle number QTLs.

QTL mapping of genotype-environment interaction for fitness in Drosophila melanogaster.

A fundamental assumption of models for the maintenance of genetic variation by environmental heterogeneity is that selection favours alternative alleles in different environments. It is not clear, however, whether such antagonistic pleiotropy is common. We mapped quantitative trait loci (QTLs) causing variation for reproductive performance in each of three environmental treatments among a set of 98 recombinant inbred (RI) lines derived from a cross between two D. melanogaster laboratory strains. The three treatments were standard medium at 25 degrees C, ethanol-supplemented medium at 25 degrees C, and standard medium at 18 degrees C. The RI lines showed highly significant genotype-environment interaction for the fitness measure. Of six QTLs with significant effects on fitness in at least one of the environments, five had significantly different effects at the different temperatures. In each case, the QTL by temperature interaction arose because the QTL had stronger effects at one temperature than at the other. No evidence for QTLs with opposite fitness effects in different environments was found. These results, together with those of recent studies of crop plants, suggest that antagonistic pleiotropy is a relatively uncommon form of genotype-environment interaction for fitness, but additional studies of natural populations are needed to confirm this conclusion.

Epistatic interactions between smell-impaired loci in Drosophila melanogaster.

Odor-guided behavior is a polygenic trait determined by the concerted expression of multiple loci. Previously, P-element mutagenesis was used to identify single P[lArB] insertions, in a common isogenic background, with homozygous effects on olfactory behavior. Here, we have crossed 12 lines with these smell impaired (smi) mutations in a half-diallel design (excluding homozygous parental genotypes and reciprocal crosses) to produce all possible 66 doubly heterozygous hybrids with P[lArB] insertions at two distinct locations. The olfactory behavior of the transheterozygous progeny was measured using an assay that quantified the avoidance response to the repellent odorant benzaldehyde. There was significant variation in general combining abilities of avoidance scores among the smi mutants, indicating variation in heterozygous effects. Further, there was significant variation among specific combining abilities of each cross, indicating dependencies of heterozygous effects on the smi locus genotypes, i.e., epistasis. Significant epistatic interactions were identified for nine transheterozygote genotypes, involving 10 of the 12 smi loci. Eight of these loci form an interacting ensemble of genes that modulate expression of the behavioral phenotype. These observations illustrate the power of quantitative genetic analyses to detect subtle phenotypic effects and point to an extensive network of epistatic interactions among genes in the olfactory subgenome.

Heterosis for viability, fecundity, and male fertility in Drosophila melanogaster: comparison of mutational and standing variation.

If genetic variation for fitness traits in natural populations ("standing" variation) is maintained by recurrent mutation, then quantitative-genetic properties of standing variation should resemble those of newly arisen mutations. One well-known property of standing variation for fitness traits is inbreeding depression, with its converse of heterosis or hybrid vigor. We measured heterosis for three fitness traits, pre-adult viability, female fecundity, and male fertility, among a set of inbred Drosophilia melanogaster lines recently derived from the wild, and also among a set of lines that had been allowed to accumulate spontaneous mutations for over 200 generations. The inbred lines but not the mutation-accumulation (MA) lines showed heterosis for pre-adult viability. Both sets of lines showed heterosis for female fecundity, but heterosis for male fertility was weak or absent. Crosses among a subset of the MA lines showed that they were strongly differentiated for male fertility, with the differences inherited in autosomal fashion; the absence of heterosis for male fertility among the MA lines was therefore not caused by an absence of mutations affecting this trait. Crosses among the inbred lines also gave some, albeit equivocal, evidence for male fertility variation. The contrast between the results for female fecundity and those for male fertility suggests that mutations affecting different fitness traits may differ in their average dominance properties, and that such differences may be reflected in properties of standing variation. The strong differentiation among the MA lines in male fertility further suggests that mutations affecting this trait occur at a high rate.

Genetic variation and causes of genotype-environment interaction in the body size of blue tit (Parus caeruleus).

In several studies of natural populations of birds, the heritability of body size estimated by parent-offspring regression has been lower when offspring have developed in poor feeding regimens than when they developed in good feeding regimens. This has led to the suggestion that adaptation under poor regimens may be constrained by lack of genetic variation. We examined the influence of environmental conditions on expression of genetic variation in body size of nestling blue tits (Parus caeruleus) by raising full sibs in artificially reduced and enlarged broods, corresponding to good and poor feeding regimens, respectively. Individuals grown in the poor regimen attained smaller body size than their sibs grown in the good regimen. However, there was among-family variation in response to the treatments--i.e., genotype-environment interactions (GEIs). Partitioning the GEI variance into contributions attributable to (1) differences in the among-family genetic variance between the treatments and (2) imperfect correlation of genotypic values across treatments identified the latter as the main cause of the GEI. Parent-offspring regressions were not significantly different when offspring were reared in the good environment (h2 = 0.75) vs. when they were reared in the poor environment (h2 = 0.63). Thus, there was little evidence that genetic variance in body size was lower under the poor conditions than under the good conditions. These results do not support the view that the genetic potential for adaptation to poor feeding conditions is less than that for adaptation to good conditions, but they do suggest that different genotypes may be favored under the different conditions.

Polygenic mutation in Drosophila melanogaster: genetic interactions between selection lines and candidate quantitative trait loci.

We have investigated genetic interactions between spontaneous mutations affecting abdominal and sternopleural bristle number that have accumulated in 12 long-term selection lines derived from an inbred strain, and mutations at 14 candidate bristle number quantitative trait loci. The quantitative test for complementation was to cross the selection lines to an inbred wild-type strain (the control cross) and to a derivative of the control strain into which the mutant allele at the candidate locus to be tested was substituted (the tester strain). Genetic interactions between spontaneous mutations affecting bristle number and the candidate locus mutations were common, and in several cases the interaction effects were different in males and females. Analyses of variance of the (tester- control) differences among and within groups of replicate lines selected in the same direction for the same trait showed significant group effects for several candidate loci. Genetically, the interactions could be caused by allelism of, and/ or epistasis between, spontaneous mutations in the selection lines and the candidate locus mutations. It is possible that much of the response to selection was from new mutations at candidate bristle number quantitative trait loci, and that for some of these loci, mutation rates were high.

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 roo 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 > or = 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: 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 F2 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.

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: estimates from response to selection of inbred strains.

Replicated divergent artificial selection for abdominal and sternopleural bristle number from a highly inbred strain of Drosophila melanogaster resulted in an average divergence after 125 generations of selection of 12.0 abdominal and 8.2 sternopleural bristles from the accumulation of new mutations affecting bristle number. Responses to selection were highly asymmetrical, with greater responses for low abdominal and high sternopleural bristle numbers. Estimates of VM, the mutational variance arising per generation, based on the infinitesimal model and averaged over the responses to the first 25 generations of selection, were 4.32 x 10(-3) VE for abdominal bristle number and 3.66 x 10(-3) VE for sternopleural bristle number, where VE is the environmental variance. Based on 10 generations of divergent selection within lines from generation 93, VM for abdominal bristle number was 6.75 x 10(-3) VE and for sternopleural bristle number was 5.31 x 10(-3) VE. However, estimates of VM using the entire 125 generations of response to selection were lower and generally did not fit the infinitesimal model largely because the observed decelerating responses were not compatible with the predicted increasing genetic variance over time. These decelerating responses, periods of response in the opposite direction to artificial selection, and rapid responses to reverse selection all suggest new mutations affecting bristle number on average have deleterious effects on fitness. Commonly observed periods of accelerated responses followed by long periods of stasis suggest a leptokurtic distribution of mutational effects for bristles.