Showing papers on "Pleiotropy published in 1994"

A genetic analysis of senescence in Drosophila

Abstract: Two attractive theories for the evolution of senescence are based on the principle that the force of natural selection decreases with age. The theories differ in the type of age-specific gene action that they assume. Antagonistic pleiotropy postulates that pleiotropic genes with positive effects early in life and negative effects of comparable magnitude late in life are favoured by selection, whereas genes with the reverse pattern of action are selected against. Mutation accumulation assumes that deleterious mutant alleles with age-specific effects will equilibrate at a lower frequency if their effects are expressed early rather than late in life. Explicit models demonstrate that both mechanisms can lead to the evolution of senescent life histories under reasonable conditions. Antagonistic pleiotropy has gained considerable empirical support, but the evidence in support of mutation accumulation is more sparse. Here we report that the genetic variability of mortality in male Drosophila melanogaster increases greatly at very late ages, as predicted by the mutation accumulation hypothesis. The rate of increase in mortality with age exhibits substantial genetic and environmental variability. This result provides a possible explanation for recent observations of non-increasing mortality rates in very old flies.

The evolution of development in drosophila melanogaster selected for postponed senescence.

Abstract: The role of development in the evolution of postponed senescence is poorly understood despite the existence of a major gerontological theory connecting developmental rate to aging. We investigate the role of developmental rate in the laboratory evolution of aging using 24 distinct populations of Drosophila melanogaster. We have found a significant difference between the larval developmental rates of our Drosophila stocks selected for early (B) and late-life (O) fertility. This larval developmental time difference of approximately 12% (O > B) has been stable for at least 5 yr, occurs under a wide variety of rearing conditions, responds to reverse selection, and is shown for two other O-like selection treatments. Emerging adults from lines with different larval developmental rates show no significant differences in weight at emergence, thorax length, or starvation resistance. Long-developing lines (O, CO, and CB) have greater survivorship from egg to pupa and from pupa to adult, with and without strong larval competition. Crosses between slower developing populations, and a variety of other lines of evidence, indicate that neither mutation accumulation nor inbreeding depression are responsible for the extended development of our late-reproduced selection treatments. These results stand in striking contrast to other recent studies. We argue that inbreeding depression and inadvertent direct selection in other laboratories' culture regimes explain their results. We demonstrate antagonistic pleiotropy between developmental rate and preadult viability. The absence of any correlation between longevity and developmental time in our stocks refutes the developmental theory of aging.

Amelioration of the deleterious pleiotropic effects of an adaptive mutation in Bacillus subtilis

Abstract: The deleterious pleiotropic effects of an adaptive mutation may be ameliorated by one of two modes of evolution: (1) by replacement, in which an adaptive mutation with harmful pleiotropic effects is replaced by one that confers an equal benefit but at less cost; or (2) by compensatory evolution, in which natural selection favors modifiers at other loci that compensate for the deleterious effects of the mutant allele. In this study, we have measured the potential of these two modes of evolution to ameliorate the deleterious pleiotropic effects of resistance to the antibiotic rifampicin in the soil bacterium Bacillus subtilis. One approach was to measure the fitness cost of a series of spontaneous rifampicin-resistance mutations from each of several strains. The potential for amelioration by the replacement mode was estimated by the variation in fitness cost among the mutants of a single strain. Another approach was to introduce a series of different rifampicin-resistance alleles into a diversity of strains, and to measure the fitness cost of rifampicin resistance for each allele-by-strain combination. The potential for amelioration by the replacement mode was estimated by the variation in fitness costs among rifampicin-resistance alleles; the potential for compensatory evolution was estimated by variation in the fitness cost of rifampicin resistance among strains. This study has shown that the cost of rifampicin resistance may be ameliorated by both the compensatory and replacement modes.

A pleiotropic phospholipid biosynthetic regulatory mutation in Saccharomyces cerevisiae is allelic to sin3 (sdi1, ume4, rpd1).

Abstract: Three mutants were identified in a genetic screen using an INO1-lacZ fusion to detect altered INO1 regulation in Saccharomyces cerevisiae. These strains harbor mutations that render the cell unable to fully repress expression of INO1, the structural gene for inositol-1-phosphate synthase. The Cpe-(constitutive phospholipid gene expression) phenotype associated with these mutations segregated 2:2, indicating that it was the result of a single gene mutation. The mutations were shown to be recessive and allelic. A strain carrying the tightest of the three alleles was examined in detail and was found to express the set of co-regulated phospholipid structural genes (INO1, CHO1, CHO2 and OP13) constitutively. The Cpe- mutants also exhibited a pleiotropic defect in sporulation. The mutations were mapped to the right arm of chromosome XV, close to the centromere, where it was discovered that they were allelic to the previously identified regulatory mutation sin3 (sdi1, ume4, rpd1, gam2). A sin3 null mutation failed to complement the mutation conferring the Cpe- phenotype. A mutant harboring a sin3 null allele exhibited the same altered INO1 expression pattern observed in strains carrying the Cpe- mutations isolated in this study.

The genetics and breeding potential of Rht12, a dominant dwarfing gene in wheat.

Abstract: Rht12, a dominant dwarfing gene of wheat, was shown to be located distally on the long arm of chromosome 5A. Lack of recombination with the awn inhibitor B1 suggested that Rht12 is cither tightly linked to this gene or is, in this material, a pleiotropic expression of the gene. Linkage to β-Amy-A1 was also very tight, indicating that Rht12 is present on the segment of chromosome SAL ancestrally translocated from 4AL. The close linkage to β-Amy-A1 also suggests that Rht12 is not a homoeoallele of the commercially important GA-insensitive dwarfing genes. Analysis of near-isogenic lines in a number of genetic backgrounds showed that Rht12 reduces height without altering ear size and significantly increases spikelet fertility. However its successful utilization in breeding programmes will require careful selection since in some backgrounds the gene reduces grain numbers and grain size. In all backgrounds, Rht12 delayed ear emergence time by around 6 days. A delay of this magnitude could, in many environments, adversely affect yield if it is not neutralized by altering the balance of other genes determining ear emergence time.

Genotype x environment interaction in QTL analysis of an intervarietal almond cross by means of genetic markers.

Abstract: Besides QTL location and the estimation of gene effects, QTL analysis based on genetic markers could be used to comprehensively investigate quantitative trait-related phenomena such as pleiotropy, gene interactions, heterosis, and genotype-by-environment interaction (G x E). Given that the G x E interaction is of great relevance in tree improvement, the objective of the research presented here was to study the effect of years on QTL detection for 15 quantitative traits by means of isozymatic markers in a large progeny group of an intervarietal cross of almond. At least 17 putative QTLs were detected, 3 of which had alleles with opposite effects to those predicted from the parental genotypes. Only 3 QTLs behaved homogeneously over the years. Three possible causes are discussed in relation to this lack of stability: the power of the test statistic being used, the low contribution of the QTL to the genetic variation of the trait, and a differential gene expression dependent on the year (G x E). Most cases showing lack of stability involved traits whose heritability estimates change drastically from year to year and/or whose correlation coefficients between years are low, suggesting the presence of G x E as the most likely cause. A marker-assisted selection scheme to improve late flowering and short flowering duration is suggested for an early and wide screening of the progeny.

The contribution of pleiotropy to blood pressure and body-mass index variation: the Gubbio Study.

Abstract: Blood pressure (BP), body-mass index (BMI), and quantitative phenotypes thought to influence BP (e.g., lithium-sodium countertransport activity) were studied in 2,184 households comprising 5,376 people in Gubbio, Italy. Variance-components models were used to partition the variation of these phenotypes into components characterizing the effects of age-related, measured environmental, additive genetic, pleiotropic, unmeasured shared-household, and individual-specific (or random) factors. The goal of the investigation was to estimate the contribution of pleiotropy to variation in BP and BMI in population-based samples. Although our results suggest that numerous significant bivariate genetic correlations exist between BP and some of the traits investigated, they ultimately lead us to reject a prominent role for any individual bivariate pleiotropic system influencing the natural variation of BP. However, because we found evidence that many traits enter into small-impact pleiotropic relationships with BP, we cannot rule out the possibility that pleiotropic genes, when considered collectively, may contribute to BP variation at the population level. Similar results were obtained when BMI was taken as the primary variable of interest. We argue that the small but significant portion of BP variation explained by individual genes displaying bivariate pleiotropic effects is intuitive, in light of the relatively low heritabilities associated with quantitative cardiovascular phenotypes and the low phenotypic correlations between BP, BMI, and many other physiologically linked measures of cardiovascular function. Our results not only bear directly on both the nature of the multifactorial determinants of BP and the maintenance of BP variation in the population at large, but also emphasize the utility of variance-components models in epidemiologic and population genetics research. We discuss the implications of our results for genetic epidemiologists and medical researchers studying hypertension, as well as the limitations of our study and areas for future research.

The population genetics of the self-incompatibility polymorphism in Papaver rhoeas . IX. Evidence of an extra effect of selection acting on the S -locus

Abstract: Investigation of the segregation ratios of the self-incompatibility (S-) alleles in three sets of full-sib families of Papaver rhoeas shows that these ratios depart significantly from Mendelian expectation. This indicates that the S-locus is subject to an extra effect of selection over and above that due to incompatibility in these families, and suggests that this is probably the chief cause of the unequal S-allele frequencies observed in the R102 and the other natural populations we have examined. Since, however, the selective advantage of an allele depends on the allele with which it is segregating in all of the families examined, the relationship between these results and the unequal 5-allele frequencies in populations appears to be complex. Furthermore, while in one family the extra effect of selection appears to be of the zygotic type, in the others it is of the gametic type - which, in most, involves the female gametophyte rather than the pollen. It is argued that the extra effect of selection is due to the linkage of the S-gene to one or more genes that are the chief target of this selection, rather than to pleiotropy. Though it is suggested that among candidates for linkage are genes controlling seed dormancy and albinism, the detection of an extra effect of selection acting on the female gametophyte and, in one case, on the pollen, implies that other genes of as yet unknown effect are more likely to be involved.

Mutation-selection balance and the evolution of senescence

Abstract: Populations of all organisms are faced with a continuous bombardment of mutations. These mutations have a range of effects from lethality to advantageous, and they have a range of pleiotropic effects as well. Population genetics theory tells us that a population in mutation-selection balance will have late-acting deleterious alleles in higher frequency than early-acting deleterious alleles. The mutation-accumulation model explains the evolution of senescence by the accumulation of late-acting deleterious alleles, and no form of pleiotropic effects needs to be specified. Alleles that cause earlier senescence can be favored by natural selection provided pleiotropic effects give those mutations a net reproductive advantage. Provided such mutations with antagonistically pleiotropic effects occur, this model may explain the evolution of senescence. To some extent, the relative importance of these two models can be inferred from the difference between the distribution of mutational effects and the equilibrium distribution of allelic effects of polymorphic loci. There are several experimental designs that, to varying degrees of success, give a quantitative assessment of the distribution of mutational effects on age-specific survival and fecundity. Thorough analysis of physiological mechanisms for senescence is highly relevant to this problem, because the mechanistic explanation for patterns of pleiotropy may be revealed by the physiology.

Correlated response to selection during selfing

Abstract: Theory for predicting the correlated response to selection during selfing is proposed and then validated by computer simulation. Pairs of characters, correlated either by pleiotropy or linkage, were simulated; linkage was in coupling, repulsion or a combination of the two. The correlated responses to both family and sib selection were examined. Comparison of expected with the average observed correlated responses showed the accuracy of the theory, but the observed sampling variation indicated that a wide variability of individual responses is to be expected in practice.