UNUSUALLY HIGH MITOCHONDRIAL ALPHA GLYCEROPHOSPHATE DEHYDROGENASE ACTIVITY IN RAT BROWN ADIPOSE TISSUE

Brown adipose tissue of the rat has been found to have an unusually high activity of mitohondrial α-glycerophosphate dehydrogenase (α-GPD) when assayed both by a histochemical staining procedure and by a quantitative biochemical method with isolated mitochondria. In contrast to succinic, glutamic, and β-hydroxybutyrate dehydrogenases, all mitochondrial enzymes, the activity of α-GPD in brown fat was 10 times that in liver, more than 20 times that in white adipose tissue, and 9 times that in kidney. The soluble NAD-linked α-GPD was also higher in brown adipose tissue than in white adipose tissue, liver, or kidney, but the differences were much less marked. The possible importance of the high activity of mitochondrial α-GPD in the regulation of synthesis of esterified lipid and in thermogenesis in brown fat is discussed.     

Metabolic control analysis as a mechanism that conserves genetic variance during advanced cycle breeding

The recycling of elite inbreds (i.e., advanced cycle breeding) has led to significant genetic gains but also to a narrow gene pool in plant breeding programs. Sustained yield improvements in many crops have suggested that genetic variance is not depleted at a rate predicted by an additive genetic model. Unlike the additive model in classical quantitative genetic theory, metabolic control analysis relates the variation in a biochemical process with the genetic variation in a quantitative trait. Our objective was to determine whether metabolic control analysis is a mechanism that slows the decrease in genetic variance during advanced cycle breeding. Three cycles of advanced cycle breeding were simulated with 10, 50, or 100 quantitative trait loci (QTL) controlling a trait. In metabolic control analysis, these QTL coded for enzymes involved in a linear metabolic pathway that converted a substrate into a product. In the absence of selection, both the additive model and the metabolic control analysis model led to about a 50% reduction in genetic variance from cycle to cycle. With selection, the additive model led to a 50–58% reduction in genetic variance, but the metabolic control analysis model generally led to only a 12–54% reduction. We suggest selection in a metabolic control analysis model as a mechanism that slows the decrease in genetic variance during advanced cycle breeding. This conservation of genetic variance would allow breeders to achieve genetic gains for a longer period than expected under the additive model.Communicated by H.C. Becker     

GENETIC COMPONENTS OF VARIATION IN ENERGY STORAGE IN DROSOPHILA MELANOGASTER

One approach to examining the underlying genetic structure of the variation in a continuous phenotype is to measure a set of possibly mechanistically related traits and determine the quantitative genetic aspects of their transmission. In this study the quantities of stored triacylglycerol and glycogen were measured along with the activities of 10 enzymes in related metabolic pathways in a set of 1,157 half-sib families of Drosophila melanogaster. The families were structured with each male being mated to 10 females and two offspring were scored from each female. Parents and offspring were scored for the phenotypes, and the components of variance (additive, dominance, and environmental) were estimated in three ways, including analysis of variance on offspring alone, parent-offspring regression, and maximum likelihood methods. While there were differences among the estimates made by the three methods, a consistent result was that substantial additive genetic variation was detected for all the traits. Consistent with models for the quantitative genetics of enzyme kinetics, the genetic variances of global properties were largely additive. Previous studies with extracted chromosome lines had indicated several significant genetic correlations among these characters, and much of the correlation was attributable to additive effects. The results imply that there is substantial opportunity for natural or artificial selection to act on quantities of stored lipid and carbohydrate, and that the response to selection is likely to be in part mediated by changes in the kinetics of the enzymes targeted in this study.     

Evolution of genetic variation for condition-dependent traits in stalk-eyed flies

Sexual selection has been proposed to increase genetic variation for condition-dependent ornaments. The condition capture model predicts the genetic variance for a sexually selected trait from the genetic variance in condition and the slope of the relationship between the ornament and condition. Assuming that body size reflects condition we assess the efficacy of this model using six species of stalk-eyed flies (Diopsidae). Prior evidence indicates that male eye span exhibits strong condition dependence and is under sexual selection in sexually dimorphic but not monomorphic species. In contrast, thorax width is weakly related to condition and probably under stabilizing selection. We estimated additive genetic variances for eye span, body length and thorax width from half-sib breeding studies and found that the condition capture model explained 97% of the variation in eye span genetic variance but only 7% of thorax width genetic variance. Comparison of phylogenetically independent contrasts revealed that evolutionary change in male eye span genetic variance is due to evolutionary change in the allometric relationship between eye span and condition: not to evolutionary change in genetic variance for condition. These results suggest that sexual selection can accelerate evolutionary change in condition-dependent male ornaments by increasing the genetic variation available for selection.     

Quantitative genetic variation in Daphnia: temporal changes in genetic architecture

Nonadditive genetic variation and genetic disequilibrium are two important factors that influence the evolutionary trajectory of natural populations. We assayed quantitative genetic variation in a temporary-pond-dwelling population of Daphnia pulex over a full season to examine the role of nonadditive genetic variation and genetic disequilibrium in determining the short-term evolutionary trajectory of a cyclic parthenogen. Quantitative traits were influenced by three factors: (1) clonal selection significantly changed the population mean phenotype during the course of the growing season; (2) sexual reproduction and recombination led to significant changes in life-history trait means and the levels of expressed genetic variation, implying the presence of substantial nonadditive genetic variation and genetic disequilibrium; and (3) Egg-bank effects were found to be an important component of the realized year-to-year change. Additionally, we examined the impact of genetic disequilibria induced by clonal selection on the genetic (co)variance structure with a common principal components model. Clonal selection caused significant changes in the (co)variance structure that were eliminated by a single bout of random mating, suggesting that a build-up of disequilibria was the primary source of changes in the (co)variance structure. The results of this study highlight the complexity of natural selection operating on populations that undergo alternating phases of sexual and asexual reproduction.     

Reconciling strong stabilizing selection with the maintenance of genetic variation in a natural population of black field crickets (Teleogryllus commodus)

Genetic variation in single traits, including those closely related to fitness, is pervasive and generally high. By contrast, theory predicts that several forms of selection, including stabilizing selection, will eliminate genetic variation. Stabilizing selection in natural populations tends to be stronger than that assumed in theoretical models of the maintenance of genetic variation. The widespread presence of genetic variation in the presence of strong stabilizing selection is a persistent problem in evolutionary genetics that currently has no compelling explanation. The recent insight that stabilizing selection often acts most strongly on trait combinations via correlational selection may reconcile this problem. Here we show that for a set of male call properties in the cricket Teleogryllus commodus, the pattern of multivariate stabilizing sexual selection is closely associated with the degree of additive genetic variance. The multivariate trait combinations experiencing the strongest stabilizing selection harbored very little genetic variation while combinations under weak selection contained most of the genetic variation. Our experiment provides empirical support for the prediction that a small number of trait combinations experiencing strong stabilizing selection will have reduced genetic variance and that genetically independent trait combinations experiencing weak selection can simultaneously harbor much higher levels of genetic variance.     

A general definition of the heritable variation that determines the potential of a population to respond to selection

Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population's intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes the concept of heritable variance to any inheritance model and level of organization. The result shows that heritable variance determining potential response to selection is the variance among individuals in the heritable quantity that determines the population mean trait value, rather than the usual additive genetic component of phenotypic variance. It follows, therefore, that heritable variance may exceed phenotypic variance among individuals, which is impossible in classical theory. This work also provides a measure of the utilization of heritable variation for response to selection and integrates two well-known models of maternal genetic effects. The result shows that relatedness between the focal individual and the individuals affecting its fitness is a key determinant of the utilization of heritable variance for response to selection.     

EVOLUTION OF PHENOTYPIC VARIANCE

A cornerstone of evolutionary theory is that the phenotypic variance of a population may be partitioned into genetic and environmental (nonheritable) components. The traditional motivation for this distinction is that the rate of evolution under natural selection depends on the (relative) magnitudes of certain genetic components of variance. The components of variation are also interesting from another perspective, as illustrated here. Phenotypic variation may be selectively maintained in a population according to its components: selection may favor the maintenance of only the environmental components, only the genetic components, or be indifferent to the composition of the variance. Even when selection is shown to favor phenotypic variation regardless of its components, the possibility exists that environmental variance will evolve to displace the genetic components or vice versa. Environmental and genetic factors may thus compete to produce a given selected level of phenotypic variance. A test of some of these models is provided from the example of seed dormancy: the prediction that variation in seed germination time should be purely environmental is supported by the demonstration of low heritability of germination time in the two available studies.     

Genetic variation in variability: Phenotypic variability of fledging weight and its evolution in a songbird population

Variation in traits is essential for natural selection to operate and genetic and environmental effects can contribute to this phenotypic variation. From domesticated populations, we know that families can differ in their level of within‐family variance, which leads to the intriguing situation that within‐family variance can be heritable. For offspring traits, such as birth weight, this implies that within‐family variance in traits can vary among families and can thus be shaped by natural selection. Empirical evidence for this in wild populations is however lacking. We investigated whether within‐family variance in fledging weight is heritable in a wild great tit (Parus major) population and whether these differences are associated with fitness. We found significant evidence for genetic variance in within‐family variance. The genetic coefficient of variation (GCV) was 0.18 and 0.25, when considering fledging weight a parental or offspring trait, respectively. We found a significant quadratic relationship between within‐family variance and fitness: families with low or high within‐family variance had lower fitness than families with intermediate within‐family variance. Our results show that within‐family variance can respond to selection and provides evidence for stabilizing selection on within‐family variance.     

Quantitative genetic variability maintained by mutation-stabilizing selection balance: sampling variation and response to subsequent directional selection

A model of genetic variation of a quantitative character subject to the simultaneous effects of mutation, selection and drift is investigated. Predictions are obtained for the variance of the genetic variance among independent lines at equilibrium with stabilizing selection. These indicate that the coefficient of variation of the genetic variance among lines is relatively insensitive to the strength of stabilizing selection on the character. The effects on the genetic variance of a change of mode of selection from stabilizing to directional selection are investigated. This is intended to model directional selection of a character in a sample of individuals from a natural or long-established cage population. The pattern of change of variance from directional selection is strongly influenced by the strengths of selection at individual loci in relation to effective population size before and after the change of regime. Patterns of change of variance and selection responses from Monte Carlo simulation are compared to selection responses observed in experiments. These indicate that changes in variance with directional selection are not very different from those due to drift alone in the experiments, and do not necessarily give information on the presence of stabilizing selection or its strength.     

Fine quantitative trait loci mapping of carbon and nitrogen metabolism enzyme activities and seedling biomass in the maize IBM mapping population

Understanding the genetic basis of nitrogen and carbon metabolism will accelerate the development of plant varieties with high yield and improved nitrogen use efficiency. A robotized platform was used to measure the activities of 10 enzymes from carbon and nitrogen metabolism in the maize (Zea mays) intermated B73 × Mo17 mapping population, which provides almost a 4-fold increase in genetic map distance compared with conventional mapping populations. Seedling/juvenile biomass was included to identify its genetic factors and relationships with enzyme activities. All 10 enzymes showed heritable variation in activity. There were strong positive correlations between activities of different enzymes, indicating that they are coregulated. Negative correlations were detected between biomass and the activity of six enzymes. In total, 73 significant quantitative trait loci (QTL) were found that influence the activity of these 10 enzymes and eight QTL that influence biomass. While some QTL were shared by different enzymes or biomass, we critically evaluated the probability that this may be fortuitous. All enzyme activity QTL were in trans to the known genomic locations of structural genes, except for single cis-QTL for nitrate reductase, Glu dehydrogenase, and shikimate dehydrogenase; the low frequency and low additive magnitude compared with trans-QTL indicate that cis-regulation is relatively unimportant versus trans-regulation. Two-gene epistatic interactions were identified for eight enzymes and for biomass, with three epistatic QTL being shared by two other traits; however, epistasis explained on average only 2.8% of the genetic variance. Overall, this study identifies more QTL at a higher resolution than previous studies of genetic variation in metabolism.     

Allozymes and fitness: Evolution of a problem

It was expected that studies of electrophoretic variability in natural populations would resolve longstanding controversies concerning the form of natural selection and its effect on genetic variance in fitness. Recent studies of fitness components for allozymes in E. coli and Drosophila, where genetic backgrounds have been rigidly controlled, and experiments designed to detect small selection coefficients, suggest that selection is much weaker than earlier investigations would indicate. However, perturbing the metabolic background associated with specific loci often allows functional differences to be amplified to an experimentally measurable level. Frequencies of null activity variants in natural populations indicate that the fitness consequences of reduced activity in heterozygoles are probably very small. These results are supported by recent theoretical considerations suggesting that the activity variation associated with electrophoretic variation will have little effect on overall flux in many pathways.     

A genetic interpretation of the variation in inbreeding depression

Inbreeding depression is expected to play an important but complicated role in evolution. If we are to understand the evolution of inbreeding depression (i.e., purging), we need quantitative genetic interpretations of its variation. We introduce an experimental design in which sires are mated to multiple dams, some of which are unrelated to the sire but others are genetically related owing to an arbitrary number of prior generations of selfing or sib-mating. In this way we introduce the concept of "inbreeding depression effect variance," a parameter more relevant to selection and the purging of inbreeding depression than previous measures. We develop an approach for interpreting the genetic basis of the variation in inbreeding depression by: (1) predicting the variation in inbreeding depression given arbitrary initial genetic variance and (2) estimating genetic variance components given half-sib covariances estimated by our experimental design. As quantitative predictions of selection depend upon understanding genetic variation, our approach reveals the important difference between how inbreeding depression is measured experimentally and how it is viewed by selection.     

The Selection Limit Due to the Conflict between Truncation and Stabilizing Selection with Mutation

Long-term selection response could slow down from a decline in genetic variance or in selection differential or both. A model of conflict between truncation and stabilizing selection in infinite population size is analysed in terms of the reduction in selection differential. Under the assumption of a normal phenotypic distribution, the limit to selection is found to be a function of kappa, the intensity of truncation selection, omega 2, a measure of the intensity of stabilizing selection, and sigma 2, the phenotypic variance of the character. The maintenance of genetic variation at this limit is also analyzed in terms of mutation-selection balance by the use of the "House-of-cards" approximation. It is found that truncation selection can substantially reduce the equilibrium genetic variance below that when only stabilizing selection is acting, and the proportional reduction in variance is greatest when the selection is very weak. When truncation selection is strong, any further increase in the strength of selection has little further influence on the variance. It appears that this mutation-selection balance is insufficient to account for the high levels of genetic variation observed in many long-term selection experiments.     

Experimental evolution of evolutionary potential in fluctuating environments

Variation is the raw material for evolution. Evolutionary potential is determined by the amount of genetic variation, but evolution can also alter the visibility of genetic variation to natural selection. Fluctuating environments are suggested to maintain genetic variation but they can also affect environmental variance, and thus, the visibility of genetic variation to natural selection. However, experimental studies testing these ideas are relatively scarce. In order to determine differences in evolutionary potential we quantified variance attributable to population, genotype and environment for populations of the bacterium Serratia marcescens. These populations had been experimentally evolved in constant and two fluctuating environments. We found that strains that evolved in fluctuating environments exhibited larger environmental variation suggesting that adaptation to fluctuations has decreased the visibility of genetic variation to selection.     

Indirect genetic effects and the spread of infectious disease: are we capturing the full heritable variation underlying disease prevalence?

Reducing disease prevalence through selection for host resistance offers a desirable alternative to chemical treatment. Selection for host resistance has proven difficult, however, due to low heritability estimates. These low estimates may be caused by a failure to capture all the relevant genetic variance in disease resistance, as genetic analysis currently is not taylored to estimate genetic variation in infectivity. Host infectivity is the propensity of transmitting infection upon contact with a susceptible individual, and can be regarded as an indirect effect to disease status. It may be caused by a combination of physiological and behavioural traits. Though genetic variation in infectivity is difficult to measure directly, Indirect Genetic Effect (IGE) models, also referred to as associative effects or social interaction models, allow the estimation of this variance from more readily available binary disease data (infected/non-infected). We therefore generated binary disease data from simulated populations with known amounts of variation in susceptibility and infectivity to test the adequacy of traditional and IGE models. Our results show that a conventional model fails to capture the genetic variation in infectivity inherent in populations with simulated infectivity. An IGE model, on the other hand, does capture some of the variation in infectivity. Comparison with expected genetic variance suggests that there is scope for further methodological improvement, and that potential responses to selection may be greater than values presented here. Nonetheless, selection using an index of estimated direct and indirect breeding values was shown to have a greater genetic selection differential and reduced future disease risk than traditional selection for resistance only. These findings suggest that if genetic variation in infectivity substantially contributes to disease transmission, then breeding designs which explicitly incorporate IGEs might help reduce disease prevalence.     

Heritabilities and additive genetic variances of the activities of some enzymes in Drosophila melanogaster populations living in different habitats

Drosophila melanogaster samples were collected from a large population in two habitats: farmyards and distilleries. Samples were taken from two villages in each habitat. Three isofemale lines were established from all four samples and full-sib crosses were set in each isofemale line. Activities of four enzymes (ADH, alpha GPDH, IDH and 6PGDH) were measured in the offspring of each cross on starch gel after electrophoresis. Broad sense heritabilities and additive genetic variances were estimated in all four samples. Most of the activity variation was observed within the isofemale lines. The isofemale lines tended to be more different in the distilleries than in the farmyards. There was no significant difference in the average activities between the two habitats for any of the enzymes investigated. The additive genetic variance of the enzyme activities did not exhibit a consistent habitat pattern. In the farmyard habitat, we detected a higher activity variation in Tiszafüred than in the other village. Strong correlation was observed among the activities of the enzymes investigated. Correlation coefficients indicated higher level of correlation in the samples collected in Tiszafüred than in those originating from Tiszaszolos. The heritability values were rather high and they had a considerable variation both between the habitats and across the enzymes.     

Comparing environmental and genetic variance as adaptive response to fluctuating selection

Phenotypic variation within populations has two sources: genetic variation and environmental variation. Here, we investigate the coevolution of these two components under fluctuating selection. Our analysis is based on the lottery model in which genetic polymorphism can be maintained by negative frequency-dependent selection, whereas environmental variation can be favored due to bet-hedging. In our model, phenotypes are characterized by a quantitative trait under stabilizing selection with the optimal phenotype fluctuating in time. Genotypes are characterized by their phenotypic offspring distribution, which is assumed to be Gaussian with heritable variation for its mean and variance. Polymorphism in the mean corresponds to genetic variance while the width of the offspring distribution corresponds to environmental variance. We show that increased environmental variance is favored whenever fluctuations in the selective optima are sufficiently strong. Given the environmental variance has evolved to its optimum, genetic polymorphism can still emerge if the distribution of selective optima is sufficiently asymmetric or leptokurtic. Polymorphism evolves in a diagonal direction in trait space: one type becomes a canalized specialist for the more common ecological conditions and the other type a de-canalized bet-hedger thriving on the less-common conditions. All results are based on analytical approximations, complemented by individual-based simulations.