Developmental effects of modifiers of the vg mutant in Drosophila melanogaster

An analysis of the modifiers affecting the expression of the vg gene was performed. We selected for weak and strong expression of the vg mutant in F2 segregating populations obtained by crossing a vestigial stock with an Oregon laboratory stock (O) and with a wild strain (B) captured near Bologna, Italy. The selection for enlarged wings was more effective in the vg B population where wild wings appeared from the 10th generation. The assay of the three major chromosomes showed that the modifiers are located on chromosomes 2 and 3. The mutant imaginal disc cell death phenotype is evident in vg/vg strains that have a wild-type wing phenotype. It is suggested that the selected modifiers do not prevent cell death but induce regenerative growth.     

The genetic basis of floral variation in Senecio jacobaea (Asteraceae).

The self-incompatible composite Senecio jacobaea (ragwort) exhibits geographic variation in the frequency of rayed and discoid (rayless) individuals. Hybrid progenies from within- and between-morph crosses were established in a seminatural (garden) environment to determine whether patterns of segregation conform to single-gene predictions (as found in other Senecio species), whether the direction of dominance is conducive to rapid evolutionary change in ray morphology, and whether geographically distant populations of the discoid morph utilize the same or different genes to suppress ray development. Data from segregating F2 and BC families were consistent with a genetic model involving one major locus and an unknown number of modifiers. Analysis of F1 progenies from different intermorph crosses using the same rayed plant as a seed parent revealed a variable and incomplete pattern of dominance, with a trend toward partial dominance in some crosses. Hybridizations between discoid populations produced a few rayed progeny (4%), but there was no tendency for the frequency of rayed progeny to increase with the geographic distance separating the parent populations. Results of this study indicate that major mutations have been important for the evolution of discoid populations of ragwort, that ray-suppressing mutations should be directly available to selection in most populations, and that the suppression of rays is conditioned by the same or similar gene(s) in Atlantic and Baltic populations of the discoid taxon.     

Premeiotic clusters of mutation and the cost of natural selection

Haldane stated that there is a cost of natural selection for new beneficial alleles to be substituted over time. Most of this cost, which leads to "genetic deaths," is in the early generations of the substitution process when the new allele is low in frequency. It depends on the initial frequency and dominance value, but not the selection coefficient, of the advantageous allele. There have been numerous suggestions on how to reduce the cost for preexisting genetic variation that goes from disadvantageous, or neutral, to advantageous with a change in the environment. However, the cost of natural selection for new alleles that arise by mutation is assumed to be high, based on the assumption that new mutant alleles arise in natural populations as single events [1/(2N) of the total alleles]. However, not all mutant alleles arise as single events. Premeiotic mutations occur frequently in individuals (germinal mosaics), giving rise to multiple copies of identical mutant alleles called a "cluster" (C) with an initial allele frequency of C/(2N) instead of 1/(2N). These clusters of new mutant alleles reduce the cost of natural selection in direct proportion to the relative size of the cluster. Hence new advantageous alleles that arise by mutation have the greatest chance of going to fixation if they occur in large clusters in small populations.     

Evolution by small steps and rugged landscapes in the RNA virus phi6

Fisher's geometric model of adaptive evolution argues that adaptive evolution should generally result from the substitution of many mutations of small effect because advantageous mutations of small effect should be more common than those of large effect. However, evidence for both evolution by small steps and for Fisher's model has been mixed. Here we report supporting results from a new experimental test of the model. We subjected the bacteriophage phi6 to intensified genetic drift in small populations and caused viral fitness to decline through the accumulation of a deleterious mutation. We then propagated the mutated virus at a range of larger population sizes and allowed fitness to recover by natural selection. Although fitness declined in one large step, it was usually recovered in smaller steps. More importantly, step size during recovery was smaller with decreasing size of the recovery population. These results confirm Fisher's main prediction that advantageous mutations of small effect should be more common. We also show that the advantageous mutations of small effect are compensatory mutations whose advantage is conditional (epistatic) on the presence of the deleterious mutation, in which case the adaptive landscape of phi6 is likely to be very rugged.     

Evolution of dominance in polymorphic Batesian mimicry

Models of two simple genetic systems of two alleles segregating at two loci are used to study the evolution of dominance of a Batesian mimic maintained in a population by frequency-dependent selection. The alleles at one locus determine the mimetic patterns, and their dominance is modified by the alleles at the other locus. In the model, the modifiers of dominance may themselves be either fully dominant or have additive effects on the dominance of the mimics. When the modifier is fully dominant in its effect on the dominance of a new mimic, the mimic will evolve dominance irrespective of the initial frequency of the modifier. When the modifiers act additively on the dominance of the mimics, a new mimic will evolve either dominance or recessiveness depending on the initial frequency of the modifiers. Unless the modifier is initially at quite a high frequency dominance will not evolve. And dominance will not evolve fully unless the modifiers are more or less selectively neutral in their effects on all other characters except the mimicry. The significance of these results is discussed with reference to the different dominance relations of the mimics in different races of the butterfly Papilio dardanus.     

The role of hybridization in evolution

Hybridization may influence evolution in a variety of ways. If hybrids are less fit, the geographical range of ecologically divergent populations may be limited, and prezygotic reproductive isolation may be reinforced. If some hybrid genotypes are fitter than one or both parents, at least in some environments, then hybridization could make a positive contribution. Single alleles that are at an advantage in the alternative environment and genetic background will introgress readily, although such introgression may be hard to detect. 'Hybrid speciation', in which fit combinations of alleles are established, is more problematic; its likelihood depends on how divergent populations meet, and on the structure of epistasis. These issues are illustrated using Fisher's model of stabilizing selection on multiple traits, under which reproductive isolation evolves as a side-effect of adaptation in allopatry. This confirms a priori arguments that while recombinant hybrids are less fit on average, some gene combinations may be fitter than the parents, even in the parental environment. Fisher's model does predict heterosis in diploid F1s, asymmetric incompatibility in reciprocal backcrosses, and (when dominance is included) Haldane's Rule. However, heterosis arises only when traits are additive, whereas the latter two patterns require dominance. Moreover, because adaptation is via substitutions of small effect, Fisher's model does not generate the strong effects of single chromosome regions often observed in species crosses.     

Influence of dominance, leptokurtosis and pleiotropy of deleterious mutations on quantitative genetic variation at mutation-selection balance

In models of maintenance of genetic variance (V (G)) it has often been assumed that mutant alleles act additively. However, experimental data show that the dominance coefficient varies among mutant alleles and those of large effect tend to be recessive. On the basis of empirical knowledge of mutations, a joint-effect model of pleiotropic and real stabilizing selection that includes dominance is constructed and analyzed. It is shown that dominance can dramatically alter the prediction of equilibrium V (G). Analysis indicates that for the situations where mutations are more recessive for fitness than for a quantitative trait, as supported by the available data, the joint-effect model predicts a significantly higher V (G) than does an additive model. Importantly, for what seem to be realistic distributions of mutational effects (i.e., many mutants may not affect the quantitative trait substantially but are likely to affect fitness), the observed high levels of genetic variation in the quantitative trait under strong apparent stabilizing selection can be generated. This investigation supports the hypothesis that most V (G) comes from the alleles nearly neutral for fitness in heterozygotes while apparent stabilizing selection is contributed mainly by the alleles of large effect on the quantitative trait. Thus considerations of dominance coefficients of mutations lend further support to our previous conclusion that mutation-selection balance is a plausible mechanism of the maintenance of the genetic variance in natural populations.     

Natural selection in populations subject to a migration load

Migration tends to oppose the effects of divergent natural selection among populations. Numerous theoretical and empirical studies have demonstrated that this migration-selection balance constrains genetic divergence among populations. In contrast, relatively few studies have examined immigration's effects on fitness and natural selection within recipient populations. By constraining local adaptation, migration can lead to reduced fitness, known as a "migration load," which in turn causes persistent natural selection. We develop a simple two-island model of migration-selection balance that, although very general, also reflects the natural history of Timema cristinae walking-stick insects that inhabit two host plant species that favor different cryptic color patterns. We derive theoretical predictions about how migration rates affect the level of maladaptation within populations (measured as the frequency of less-cryptic color-pattern morphs), which in turn determines the selection differential (the within-generation morph frequency change). Using data on color morph frequencies from 25 natural populations, we confirm previous results showing that maladaptation is higher in populations receiving more immigrants. We then present novel evidence that this increased maladaptation leads to larger selection differentials, consistent with our model. Our results provide comparative evidence that immigration elevates the variance in fitness, which in turn leads to larger selection differentials, consistent with Fisher's Theorem of Natural Selection. However, we also find evidence that recurrent adult migration between parapatric populations may tend to obscure the effects of selection.     

Evolved aniline catabolism in Acinetobacter calcoaceticus during continuous culture of river water

Adaptation of Acinetobacter calcoaceticus from river water to aniline depends on the dynamics of parent and mutant populations. The parent, Acinetobacter strain DON26 phenotype Ani0, was common in river water and assimilated aniline effectively at micromolar concentrations, but was inhibited at higher concentrations of aniline. The Ani0 phenotype was also characterized by a broad specificity for oxidation of chloroanilines by aniline-induced cells. The mutant Ani+ phenotype was represented by DON2, isolated from a population of less than 100 cells ml-1 in a mixed river water culture, and by DON261, isolated during continuous culture of DON26. Ani+ strains assimilated aniline at a greater maximum specific rate than the parent and were able to grow at concentrations of aniline greater than 16 mM. These strains cooxidized phenol after growth at high aniline concentrations, but showed reduced activity toward chloroanilines. These changes plus kinetic data, oxygen uptake data, and the results of auxanography indicate that the mutant has an increased activity and altered specificity of the initial enzyme in the aniline catabolic pathway. The parent strain, DON26, was at a selective advantage relative to the mutant at low concentrations of aniline, but was replaced by the mutant when aniline concentrations increased. Adaptation of the mixed river water community to aniline involved selection of both phenotypes. Reversion of the Ani+ to Ani0 phenotype occurred at a frequency of 10(-2) in the absence of aniline selection. Plasmid content was not altered during either acquisition or loss of the Ani+ phenotype. Adaptive changes in Acinetobacter spp. populations illustrate important differences in the catabolic activities of natural and pollutant selected strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolved aniline catabolism in Acinetobacter calcoaceticus during continuous culture of river water.

Adaptation of Acinetobacter calcoaceticus from river water to aniline depends on the dynamics of parent and mutant populations. The parent, Acinetobacter strain DON26 phenotype Ani0, was common in river water and assimilated aniline effectively at micromolar concentrations, but was inhibited at higher concentrations of aniline. The Ani0 phenotype was also characterized by a broad specificity for oxidation of chloroanilines by aniline-induced cells. The mutant Ani+ phenotype was represented by DON2, isolated from a population of less than 100 cells ml-1 in a mixed river water culture, and by DON261, isolated during continuous culture of DON26. Ani+ strains assimilated aniline at a greater maximum specific rate than the parent and were able to grow at concentrations of aniline greater than 16 mM. These strains cooxidized phenol after growth at high aniline concentrations, but showed reduced activity toward chloroanilines. These changes plus kinetic data, oxygen uptake data, and the results of auxanography indicate that the mutant has an increased activity and altered specificity of the initial enzyme in the aniline catabolic pathway. The parent strain, DON26, was at a selective advantage relative to the mutant at low concentrations of aniline, but was replaced by the mutant when aniline concentrations increased. Adaptation of the mixed river water community to aniline involved selection of both phenotypes. Reversion of the Ani+ to Ani0 phenotype occurred at a frequency of 10(-2) in the absence of aniline selection. Plasmid content was not altered during either acquisition or loss of the Ani+ phenotype. Adaptive changes in Acinetobacter spp. populations illustrate important differences in the catabolic activities of natural and pollutant selected strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolutionary Dynamics of Sporophytic Self-Incompatibility Alleles in Plants

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.     

A TEST OF THE ROLE OF EPISTASIS IN DIVERGENCE UNDER UNIFORM SELECTION

Five populations of Drosophila melanogaster have previously been shown to be replicably different in their responses to artificial selection for knockdown resistance to ethanol fumes (Cohan and Hoffmann, 1986). The present study tests whether this divergence could be attributed to the epistatic mechanism assumed by Wright's shifting-balance model of evolution, in which alleles favored in the genetic background of one population are not favored in that of another. If this were the mechanism of divergence, crosses between selected lines from different populations would be expected to yield an epistatic loss of the selected phenotype. However, all such crosses showed a good fit to an additive model with dominance. Divergence by an epistatic mechanism may also be associated with epistatic variance within populations, but no evidence for such epistasis was found. The populations therefore appear to have responded in different ways to selection not because of epistasis but because knockdown-resistance alleles that were common in some populations were absent (or at least less common) in others.     

On the evolution of dominance modifiers I. A nonlinear analysis

A well known mathematical model of evolution of dominance is subjected to a nonlinear analysis. For the case where the primary locus and the modifying locus are completely linked (r = 0) a global Ljapunov function is given. This proves that selection of dominance modifiers entirely due to their modifying effect is possible. This result is also extended to small recombination fractions r by using the method of Ljapunov functions in a more sophisticated way. For r = 0 and μ = 0 a lower bound for the success of selection of the modifier is given. Furthermore, the influence of the dominance relations between the alleles (measured by the parameters h and k) is investigated. Finally it is shown that differential and difference equations lead to the same results (which need not be the case in general). As a by-product we obtain a new equilibrium point in the classical one locus selection-mutation model.     

Evolution of dominance under frequency-dependent intraspecific competition

A population-genetic analysis is performed of a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under frequency-dependent disruptive selection caused by intraspecific competition for a continuum of resources. The modifier locus determines the degree of dominance at the trait level. We establish the conditions when a modifier allele can invade and when it becomes fixed if sufficiently frequent. In general, these are not equivalent because an unstable internal equilibrium may exist and the condition for successful invasion of the modifier is more restrictive than that for eventual fixation from already high frequency. However, successful invasion implies global fixation, i.e., fixation from any initial condition. Modifiers of large effect can become fixed, and also invade, in a wider parameter range than modifiers of small effect. We also study modifiers with a direct, frequency-independent deleterious fitness effect. We show that they can invade if they induce a sufficiently high level of dominance and if disruptive selection on the ecological trait is strong enough. For deleterious modifiers, successful invasion no longer implies global fixation because they can become stuck at an intermediate frequency due to a stable internal equilibrium. Although the conditions for invasion and for fixation if sufficiently frequent are independent of the linkage relation between the two loci, the rate of spread depends strongly on it. The present study provides further support to the view that evolution of dominance may be an efficient mechanism to remove unfit heterozygotes that are maintained by balancing selection. It also demonstrates that an invasion analysis of mutants of very small effect is insufficient to obtain a full understanding of the evolutionary dynamics under frequency-dependent selection.     

Effect of gametic disequilibrium on selection in an autotetraploid population

Summary The effects of a gametic disequilibrium (DSE) in an autotetraploid population on response to selection as measured by the covariance of selection were investigated. The theoretical responses were calculated for mass selection [Mass (1)] and half-sib progeny test selection (HSPT) in a two-allele (B and b), single locus, autotetraploid population. The complexity of calculations precluded analytical expressions for the covariances so numerical analysis was used assuming the following genetic models: monoplex dominance, partial monoplex dominance, duplex dominance, partial duplex dominance, and additive gene action.The results indicated the DSE could greatly affect the covariance of selection. For a constant allele frequency the DSE might double the covariance expected with selection in a population at random mating equilibrium (RME) of gametes, but in other instances approach zero. For all genetic models and the two breeding methods investigated the covariance of selection was always increased when the frequency of BB gamete exceeded p² (where p is frequency of allele B) and decreased when the frequency of BB gamete was less than p². The possible incorporation of this information into a long term breeding program and some other ramifications were briefly discussed.With the DSE the covariances of selection with HSPT and Mass (1) had a proportionality of 1:2, respectively, with the additive genetic model, but this relationship rarely occurred for other genetic models. The deviations from this ratio were not large in comparison to differences between selection in populations in DSE and RME.Cooperative investigations of the Alfalfa Production Research Unit, United State Department of Agriculture, Agricultural Research Service, and the Nevada Agricultural Experiment Station, Reno, Nevada. Paper No. 512. Scientific Journal Series, Nevada Agricultural Experiment Station     

Monogenic Recessive Mutations Causing Both Late Floral Initiation and Excess Starch Accumulation in Arabidopsis

A recessive Arabidopsis mutation, carbohydrate accumulation mutant1 (cam1), which maps to position 22.8 on chromosome 3, was identified by screening leaves of ethyl methanesulfonate-mutagenized M2 plants stained with iodine for altered starch content. Increased starch content in leaves of the cam1 mutant was observed at the onset of flowering. This mutant also had a delayed floral initiation phenotype with more rosette leaves than the parental line. In addition, activities of several enzymes associated with starch metabolism were altered in the cam1 mutant. The late-flowering mutant gigantea (gi) also manifested an elevated starch level in leaves. However, not all late-flowering mutants had increased leaf starch content. Double mutants cam1 adg1 (for ADP-glucose pyrophosphorylase), cam1 pgm (for phosphoglucomutase), and gi pgm had no observable starch in leaves but showed the late-flowering phenotype, demonstrating that the elevated starch content is not the cause of late floral initiation. The pleiotropic effects of cam1 and gi suggest that they may play regulatory roles in starch metabolism and floral initiation. These data suggest that starch accumulation and floral initiation may share a common regulatory pathway.     

INBREEDING DEPRESSION,GENETIC LOAD,AND THE EVOLUTION OF OUTCROSSING RATES IN A MULTILOCUS SYSTEM WITH NO LINKAGE

We studied deterministic models of multilocus systems subject to mutation–selection balance with all loci unlinked, and with multiplicative interactions of the loci affecting fitness, in partially self-fertilizing populations. The aim was to examine the fitnesses of the zygotes produced by outcrossing and by selling, and the magnitude of inbreeding depression, in populations with different levels of inbreeding. The fates of modifiers of the outcrossing rate were also examined. With biologically plausible parameter values, inbreeding depression can be very large in moderately selfing populations, particularly when the mutant alleles are fairly recessive and selection is weak. A modifier allele reducing the selfing rate can be favored under these circumstances. In more inbred populations, inbreeding depression is lower, and selection favors alleles that increase the selfing rate. When inbreeding depression is caused by mutant alleles with strong selective disadvantage, modifiers causing large increases in selfing can often be favored even when the inbreeding depression exceeds one-half, though in these circumstances modifiers increasing selfing by smaller amounts are usually eliminated. Weaker selection appears to be more favorable to the maintenance of outcrossing.     

Mitochondrial DNA defects in Saccharomyces cerevisiae caused by functional interactions between DNA polymerase gamma mutations associated with disease in human

The yeast mitochondrial DNA (mtDNA) replicase Mip1 has been used as a model to generate five mutations equivalent to POLG mutations associated with a broad spectrum of diseases in human. All mip1 mutations, alone or in combination in cis or in trans, increase mtDNA instability as measured by petite frequency and Ery(R) mutant accumulation. This phenotype is associated with decreased Mip1 levels in mitochondrial extracts and/or decreased polymerase activity. We have demonstrated that (1) in the mip1(G651S) (hG848S) mutant the high mtDNA instability and increased frequency of point Ery(R) mutations is associated with low Mip1 levels and polymerase activity; (2) in the mip1(A692T-E900G) (hA889T-hE1143G) mutant, A692T is the major contributor to mtDNA instability by decreasing polymerase activity, and E900G acts synergistically by decreasing Mip1 levels; (3) in the mip1(H734Y)/mip1(G807R) (hH932Y/hG1051R) mutant, H734Y is the most deleterious mutation and acts synergistically with G807R as a result of its dominant character; (4) the mip1(E900G) (h1143G) mutation is not neutral but results in a temperature-sensitive phenotype associated with decreased Mip1 levels, a property explaining its synergistic effect with mutations impairing the polymerase activity. Thus, the human E1143G mutation is not a true polymorphism.     

Sex ratios in geographically structured populations

In his book on sexual selection (1), Darwin documented evidence that the primary sex ratio (the proportion of males at conception) is about 1/2 in a wide variety of species. Otherwise, he explained, a newly conceived member of the rare sex will, on average, have more offspring than one of the common sex, since each offspring has one mother and one father; thus there is frequency-dependent selection in favour of parents producing the rare sex. Darwin formulated this explanation in the first edition (1871) for monogamous species, but he failed to extend it to polygamous species, and in the second edition (1874) he retracted it completely. It was left to Fisher (2) to develop the theory in the more general form that there should be equal parental expenditure on the two sexes, allowing for the possibility that one sex may cost more to produce than the other. Despite the wide applicability of Fisher's principle, recent work on sex ratio evolution has focused on situations where it breaks down (3). Hamilton (4) first pointed out that Fisher's argument assumes population-wide competition for mates, whereas most natural populations have a geographical population structure in which limited dispersal imposes constraints on mating patterns. What are the consequences for the sex ratio?