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Biomedical subjects

J W Curtsinger

Publications and source records attributed to J W Curtsinger.

At least 37 records · Page 2Linked to original sources
PubMed1995

Density and age-specific mortality.

Age-specific mortality rates decelerate at older ages in laboratory populations in the Medfly Ceratitis capitata. This has been interpreted by Carey et al. (1992) to reflect a slowing of the aging process, but might also be explained by declining adult density. Here it is argued that the density explanation, as presented by Graves and Mueller (1993), is unpersuasive for several reasons: extrapolations from Drosophila to Medflies are unjustified; the range of densities they studied is 2-120 times higher than that used in other studies; they ignore data on Medflies held in isolation, which rule out density effects; their own data suggest that initial cohort density has no effect on mortality rates at older ages, which is the relevant part of the life cycle; their experiment is too small to provide accurate estimates of mortality; new Medfly experiments executed at multiple densities show decelerating and then declining mortality rates at advanced ages for all densities. When Drosophila survivorship experiments are done on a sufficiently large scale they also show a deceleration of mortality at older ages that is not attributable to density effects. The deceleration of mortality rates is most likely a real facet of aging, and will have to be taken into consideration in any synthesis of the genetics and evolution of aging.

Aging↗
PubMed1995

Effect of adult cohort density on age-specific mortality in Drosophila melanogaster.

Mortality rates decelerate at older ages in experimental populations of Drosophila. It is unclear whether this reflects a real slow-down in the aging process, or an artifact of declining density. Mortality was studied in age-synchronized cohorts of four inbred lines at three initial densities that varied 10-fold. A total of 70,000 flies of both sexes were studied. There were large line x density, line, and sex effects, but no systematic relationship between density and life span was detected. Mortality curves level off at older ages in 23 out of 24 sex-genotype combinations, irrespective of initial cohort density. Density has only second-order effects on the pattern of oldest-old mortality over the range of densities studied here. The dramatic departure from Gompertz-type mortality dynamics at older ages is not an artifact of declining density in Drosophila.

Aging↗
PubMed1995

Genetic variation and aging.

Life span is subject to genetic modification in yeasts, nematodes, fruit flies, mice, humans, and other vertebrates and invertebrates. There are a few single-gene mutants known that extend life span in yeast and nematodes; in other experimental systems the character is treated quantitatively, and generally has a low to moderate heritability. Life span responds to artificial selection in Drosophila and Caenorhabditis. There are many candidate genes presently under investigation, including the anti-oxidizing enzymes and heat-shock proteins. The main evolutionary models of senescence are antagonistic pleiotropy and mutation accumulation, neither of which has substantial experimental support. The incorporation of analytical techniques from demography is playing an increasing role in research on aging.

Aging↗
PubMed1995

Selection for increased longevity in Drosophila melanogaster: a response to Baret and Lints.

Baret and Lints [Gerontology 1993;39:252-259] have questioned the interpretation of artificial selection experiments for increased longevity in Drosophila. They suggest that such experiments cannot demonstrate the genetic determination of longevity, because line differences in mean longevity are confounded with erratic temporal variations in life span. Using 15,000 flies from selected and control lines developed by Luckinbill and Clare [Heredity 1985;55:9-19], we show here that when lines are tested simultaneously in a carefully controlled environment, they exhibit markedly different average life spans: selected males live 20 days longer than controls, and selected females live 10 days longer. These and other observations leave no doubt about the existence of heritable variation influencing longevity in Drosophila.

Animals↗
PubMed1995

Survival curves subjected to occasional insults.

We describe a parametric family of survival curves which can be used to model time to event data in systems subjected to occasional insults or shocks. Parameters control the location, magnitude, and duration of the effect for each insult. We use these models to describe the survival history of a large cohort of Drosophila that were transferred to new vials on a weekly basis as their nutrient medium deteriorated. A periodic model with fewer parameters exhibits a good fit to the data.

Animals↗
PubMed1994

Piecewise exponential survival curves with smooth transitions.

Several models of a population survival curve composed of two piecewise exponential distributions are developed. In one formulation the hazard rate changes at a point that is an unobservable random variable that varies between individuals. The population hazard function may decrease with age even when all individuals' hazards are increasing. In a second formulation, the population hazard function is modeled directly. Several models are fit to the survival history of a cohort of 5751 highly inbred male Drosophila melanogaster and the British coal mining disaster data.

Animals↗
PubMed1992

Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster.

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest age.

Aging↗
PubMed1990

Genotype and anesthetic determine mate choice in Drosophila melanogaster.

Genetic differences that influence mating preferences were studied in genetically defined lines of Drosophila melanogaster. Initial results suggested substantial differences between two types of females with respect to the types of male preferred as mates, but further experimentation showed that the mating patterns were conditional on the mode of anesthesia (CO2 versus ether). In a statistical test of independence, the major determinant of mating choice in these experiments was due to an interaction effect between genotypes and mode of anesthesia. The observations might be explained by the differential sensitivity of male genotypes to ether. Etherization at emergence has lasting effects on mating behavior; it alters not only the latency and frequency of mating 4 days later, but also the pattern of matings observed.

Animals↗
PubMed1986

Relationship between alpha-glycerophosphate dehydrogenase activity and metabolic rate during flight in Drosophila melanogaster.

Measurements of wing-beat frequency (WBF) have been used to characterize flight muscle metabolic rate in Drosophila melanogaster during tethered flight. Progeny of crosses between 17 X-chromosome substitution lines and three null-activity stocks have been studied in order to determine the effect on flight metabolism of sharply reduced activity of alpha-glycerophosphate dehydrogenase (alpha GPDH). It was found that flies with an approximate 50% reduction in alpha GPDH activity have a metabolic rate that is, in most cases, indistinguishable from that of wild-type flies and, in the most extreme cases, reduced by only 4%. These results demonstrate that alpha Gpdh is not a "major gene" for flight metabolism, in the quantitative genetic sense of the term. These results are in agreement with the Kacser and Burns (1973, 1979, 1981) theory of flux, which postulates that the activity of an enzyme embedded in a multienzyme pathway can sometimes vary from wild-type to very low levels (perhaps 5-10% wild type) with no significant effect on flux through the total pathway.

Alleles↗
PubMed1985

Genetic variability of flight metabolism in Drosophila melanogaster. II. Relationship between power output and enzyme activity levels.

The major goal of the studies reported here was to determine the extent to which genetic variation in the activities of the enzymes participating in flight metabolism contributes to variation in the mechanical power output of the flight muscles in Drosophila melanogaster. Isogenic chromosome substitution lines were used to partition the variance of both types of quantitative trait into genetic and environmental components. The mechanical power output was estimated from the wingbeat frequency, wing amplitude and wing morphology of tethered flies by applying the aerodynamic models of Weis-Fogh and Ellington. There were three major results. (1) Chromosomes sampled from natural populations provide a large and repeatable genetic component to the variation in the activities of most of the 15 flight metabolism enzymes investigated and to the variation in the mechanical power output of the flight muscles. (2) The mechanical power output is a sensitive indicator of the rate of flight metabolism (i.e., rate of oxygen consumption during tethered flight). (3) In spite of (1) and (2), no convincing cases of individual enzyme effects on power output were detected, although the number and sign of the significant enzyme-power correlations suggests that such effects are not totally lacking.

Animals↗
PubMed1984

Evolutionary principles for polynomial models of frequency-dependent selection.

A one-locus two-allele deterministic model of frequency-dependent selection is analyzed, where genotypic fitnesses [w(i)(q)] are assumed to be nth-degree polynomial functions of allelic frequency (q). The model encompasses many modes of selection, including intraspecies competitive interaction, brood selection, meiotic drive, cyclical selection, and mixed models. Allelic frequencies converge monotonically to locally stable equilibria provided that dw(i)(q)/dq is not large. There exists a function T(q) that is nondecreasing and locally maximized at locally stable equilibria. The rate of change of T(q) per generation is approximately equal to the additive genetic variance in fitness. T(q) is a simple function of the average effect of an allelic substitution and is closely related to Wright's "fitness function." These results define "evolutionary landscapes" for some complex selection processes and enlarge the scope of the classical methods embodied in Wright's "mean fitness principle" and Fisher's "fundamental theorem."

Journal Article↗
PubMed1984

Components of selection in X chromosome lines of Drosophila melanogaster: sex ratio modification by meiotic drive and viability selection.

Selection coefficients and segregation parameters have been estimated in 18 randomly chosen lines carrying wild X chromosomes on the cn bw genetic background. Each line was studied in replicated crosses of four types, with approximately 100 replications per line per cross. Crosses in which male X chromosomes differed exhibited significant sex ratio heterogeneity. Maximum likelihood estimation of segregation parameters revealed two lines in which the proportion of X-bearing gametes produced by males was significantly different from Mendelian expectations. These observations suggest that segregation distortion is a common feature of naturally occurring genetic variation. Non-Mendelian segregation has important evolutionary implications.

Animals↗
PubMed1983

A two-generation study of human sex-ratio variation.

We report here the first vertical population study of human sex-ratio variation. Sex-ratio data for 2 generations from Akita, Japan, have been analyzed. Parental age, birth order, sequences of the sexes at birth, and generations have no statistically significant effect on sex ratio. There is a slight excess of males at birth, as is typical for human sex-ratio studies. There is evidence of sex-ratio-dependent family planning. An analysis of vertical transmission of sex-ratio modifying factors that excludes effects of birth order in both the parental and offspring generations has detected a marginally significant paternal effect. Genetic variability of the sex ratio, if present at all, is of a very minor magnitude.

Adult↗
PubMed1982

Naturally occurring enzyme activity variation in Drosophila melanogaster. I. Sources of variation for 23 enzymes.

The genetic component of variation of enzyme activity levels in Drosophila melanogaster was investigated by using 48 second- and 48 third-chromosome isogenic substitution lines derived from natural populations. The results confirm those of our earlier experiments with the same lines and extend them to a number of additional enzymes. All 23 enzymes show a significant genetic component to the variation in one or both sets of lines and only a small part of this variation is accounted for by variation among the lines in the amount of tissue per fly. The magnitude of line effects is, in most cases, considerably larger than the magnitude of environmental and measurement error effects, and the line effects are approximately continuous in distribution. Variation in the geographic origin and karyotype of the chromosomes generally does not contribute to the line component of variation, but allozymes provide an important source of variation for a few of the enzymes. Many of the enzymes show evidence for variation of activity modifiers that are not linked to the structural locus of the enzyme.

Animals↗
PubMed1982

Naturally occurring enzyme activity variation in Drosophila melanogaster. II. Relationships among enzymes.

This report describes an investigation of the specificities of the genetic effects, caused by whole chromosome substitution, on the activities of 23 enzymes in Drosophila melanogaster. Two types of correlation estimates are examined, the product-moment correlation over the chromosome substitution line means and the corresponding correlation of line effects, which is a standardized covariance component estimate. The two types of correlations give very similar results. Although there is ample evidence for specific line effects on individual enzyme activities, there are extensive intercorrelations among many of the enzymes for both second- and third-chromosome substitution lines. The pattern of correlations with respect to the metabolic functions or other properties of the enzymes is difficult to visualize by inspection of the correlation matrix, so a multivariate graphical technique, the biplot (GABRIEL 1971), was employed to obtain a two-dimensional view of relationships among the enzyme activities. The second and third chromosome lines show similar patterns. Four of the five mitochondrial enzymes form one highly intercorrelated group whereas another highly intercorrelated group contains several cytosolic enzymes. Within the cytosolic group, particularly high correlations are observed between enzymes that have glucose 6-phosphate as a substrate or product and between enzymes that are NADP-dependent. Although the pattern of intercorrelations is not clearly explicable in terms of metabolic relationships among the enzymes, there is some tendency for enzymes that catalyze sequential reactions or share a substrate or product to have correlated activity levels.

Chromosome Mapping↗
PubMedDate not supplied

Slowing of age-specific mortality rates in Drosophila melanogaster.

We have studied age-dependent mortality in large cohorts of male and female D. melanogaster from four inbred lines. Average longevity varies substantially between genotypes (broad-sense heritability = 22%). Contrary to the predictions of the Gompertz model, mortality rates tend to decelerate at the most advanced ages. Fitting Gompertz, Weibull, Logistic, and Two-stage Gompertz mortality models to the data, we find that the best fit is obtained with the two-stage model, with exponentially increasing mortality at early ages, and zero or nearly zero increase at older ages. There is little microenvironmental effect from cage to cage. There is a sex-dependent mortality crossover: males and females differ in initial mortality rate and degree of acceleration of mortality rate, but the ordering of the sexes according to mortality parameters depends on genotype. Model fitting can be affected by gaps between deaths in the tail of the survivorship distribution. The observations are inconsistent with the limited life-span paradigm, which predicts sudden and well-defined drops in survivorship and corresponding sharp increases in mortality at advanced ages for large cohorts of genetically identical individuals.

Age Factors↗
PubMedDate not supplied

Stress experiments as a means of investigating age-specific mortality in Drosophila melanogaster.

Age-specific mortality rates level off at older ages in genetically homogeneous experimental populations of Drosophila. Here we describe an experiment that is informative about the causes of mortality rate changes. By applying a brief, nondebilitating stress that increases mortality early in life and then observing subsequent mortality trajectories, it is possible to determine whether populations are heterogeneous for factors influencing mortality. We show that 24-h exposure to a desiccating air flow causes a spike and then a decrease in mortality rates in experimental populations compared to controls. If there is no stress-induced enhancement of vitality, then the results demonstrate the existence of heterogeneity for mortality rates in genetically homogeneous populations.

Aging↗