Biomedical subjects

Michael R Rose

Publications and source records attributed to Michael R Rose.

29 records · Page 2Linked to original sources

PubMed2003

The devil in the details of life-history evolution: instability and reversal of genetic correlations during selection on Drosophila development.

The evolutionary relationships between three major components of Darwinian fitness, development rate, growth rate and preadult survival, were estimated using a comparison of 55 distinct populations of Drosophila melanogaster variously selected for age-specific fertility, environmental-stress tolerance and accelerated development. Development rate displayed a strong net negative evolutionary correlation with weight at eclosion across all selection treatments, consistent with the existence of a size-versus-time tradeoff between these characters. However, within the data set, the magnitude of the evolutionary correlation depended upon the particular selection treatments contrasted. A previously proposed tradeoff between preadult viability and growth rate was apparent only under weak selection for juvenile fitness components. Direct selection for rapid development led to sharp reductions in both growth rates and viability. These data add to the mounting results from experimental evolution that illustrate the sensitivity of evolutionary correlations to (i) genotype-by-environment (G x E) interaction, (ii) complex functional-trait interactions, and (iii) character definition. Instability, disappearance and reversal of patterns of genetic covariation often occur over short evolutionary time frames and as the direct product of selection, rather than some stochastic process. We suggest that the functional architecture of fitness is a rapidly evolving matrix with reticulate properties, a matrix that we understand only poorly.

Animals↗

PubMed2003

Statistical tests of demographic heterogeneity theories.

In this paper we develop predictions from models of life-long demographic heterogeneity. These predictions are then compared to observations of mortality in large laboratory populations of Drosophila melanogaster. We find that the demographic heterogeneity models either require levels of variation that far exceed what would be considered biologically plausible, or they predict a much larger number of very old individuals than we actually observe. We conclude that the demographic heterogeneity models are not reasonable explanations of demographic patterns and are weakly motivated biological models.

Aging↗

PubMed2003

Breakdown in correlations during laboratory evolution. I. Comparative analyses of Drosophila populations.

We provide evidence from comparisons of populations of Drosophila that evolutionary correlations between longevity and stress resistance break down over the course of laboratory evolution. Using 15 distinct evolutionary regimes, we created 75 populations that were differentiated for early fecundity, longevity, starvation resistance, desiccation resistance, and developmental time. In earlier experiments, selection for postponed aging produced increases in stress resistance, whereas selection for increased stress resistance produced increases in longevity. Direct estimates of correlations also indicated an antagonistic relationship between early fecundity on one hand and longevity or stress resistance on the other. Laboratory evolution of extreme values of stress resistance, however, led to a breakdown in these evolutionary relationships. There was no evidence that these significant changes in correlation resulted from genotype-by-environment interactions or inbreeding. These findings suggest that correlations between functional characters are not necessarily durable features of a species, and that short-term evolutionary responses cannot be extrapolated reliably to longer-term evolutionary patterns.

Animals↗

PubMed2003

Breakdown in correlations during laboratory evolution. II. Selection on stress resistance in Drosophila populations.

We trace the evolutionary correlation between stress resistance and longevity in populations of Drosophila melanogaster selected for stress resistance over many generations. Females selected for desiccation resistance and both females and males selected for increasing starvation resistance initially show concurrent increases in longevity, but then begin to decrease in longevity, even as stress resistance continues to increase. We demonstrate that the correlation between two fitness traits can change and that this change is due to sustained selection rather than a genotype-by-environment interaction or inbreeding depression. The breakdown in evolutionary correlation we report underscores the difficulty of extrapolating the results from short-term selection experiments to predictions of long-term evolution.

Animals↗

PubMed2002

Ageing: the many-headed monster.

Ageing involves numerous pathways that are not functionally coordinated. The genome-wide profiling of transcription during Drosophila ageing is proving to be a powerful new tool for identifying these pathways.

Aging↗

PubMed2002

Doxycycline-induced expression of sense and inverted-repeat constructs modulates phosphogluconate mutase (Pgm) gene expression in adult Drosophila melanogaster.

BACKGROUND: A tetracycline-regulated (conditional) system for RNA interference (RNAi) would have many practical applications. Such a strategy was developed using RNAi of the gene for phosphogluconate mutase (Pgm). Pgm is a candidate lifespan regulator: PgmS allele frequency is increased by selection for increased lifespan, whereas PgmM and PgmF allele frequencies are decreased. RESULTS: The Pgm alleles were cloned and sequenced and were found to differ by amino-acid substitutions consistent with the relative electrophoretic mobilities of the proteins. The 'tet-on' doxycycline-regulated promoter system was used to overexpress PgmS in a wild-type (PgmM) background. Enzyme activity increases of two- to five-fold were observed in five independent transgenic lines. Tet-on was also used to drive expression of an inverted-repeat fragment of Pgm coding region. The inverted-repeat transcript was expected to form a dsRNA hairpin, induce RNAi, and thereby reduce endogenous Pgm gene expression at the RNA level. Endogenous Pgm RNA levels in adult flies were found to be reduced or eliminated by doxycycline treatment in five independent inverted-repeat transgenic lines. Our results show that doxycycline-regulated expression of inverted-repeat constructs can cause a conditional reduction in specific gene expression. The effect of sense and inverted-repeat construct expression on lifespan was assayed in multiple transgenic lines. Under the conditions tested, altered Pgm gene expression had no detectable effect on adult Drosophila lifespan. CONCLUSIONS: A system for conditional RNAi in Drosophila adults shows promise for assay of gene functions during aging. Our results indicate that Pgm does not have a simple strong effect on longevity.

Aging↗

PubMed2002

Pharmacology, genomics, and the evolutionary biology of ageing.

Aging is a multifold process affected by many genes and thus many biochemical pathways. This conclusion is underscored by the failure to find simple central controls for the aging process during the 20th Century. This situation poses a fundamental challenge to anti-aging medicine: how to develop effective therapies for a genomically complex pathology. We propose such a strategy. As a first step, we recommend the use of model systems in which significant genetic intervention is not proscribed or impractical. Second, we propose that work with such model systems begin with selected lines that have genetic enhancements that allow increased lifespan. Third, genomic methods should be used to identify a number of biochemical pathways for increasing lifespan. Fourth, biochemical pathways that have been identified in model systems would then be available for pharmaceutical development, first in rodents, eventually in a clinical human population. This may seem to be a cumbersome R&D strategy, but starting with human populations or inadequately pre-screened compounds would be unlikely to succeed because of the complexity of the aging problem.

Aging↗

PubMed2002

Evolution of late-life mortality in Drosophila melanogaster.

Aging appears to cease at late ages, when mortality rates roughly plateau in large-scale demographic studies. This anomalous plateau in late-life mortality has been explained theoretically in two ways: (1) as a strictly demographic result of heterogeneity in life-long robustness between individuals within cohorts, and (2) as an evolutionary result of the plateau in the force of natural selection after the end of reproduction. Here we test the latter theory using cohorts of Drosophila melanogaster cultured with different ages of reproduction for many generations. We show in two independent comparisons that populations that evolve with early truncation of reproduction exhibit earlier onset of mortality-rate plateaus, in conformity with evolutionary theory. In addition, we test two population genetic mechanisms that may be involved in the evolution of late-life mortality: mutation accumulation and antagonistic pleiotropy. We test mutation accumulation by crossing genetically divergent, yet demographically identical, populations, testing for hybrid vigor between the hybrid and nonhybrid parental populations. We found no difference between the hybrid and nonhybrid populations in late-life mortality rates, a result that does not support mutation accumulation as a genetic mechanism for late-life mortality, assuming mutations act recessively. Finally, we test antagonistic pleiotropy by returning replicate populations to a much earlier age of last reproduction for a short evolutionary time, testing for a rapid indirect response of late-life mortality rates. The positive results from this test support antagonistic pleiotropy as a genetic mechanism for the evolution of late-life mortality. Together these experiments comprise the first corroborations of the evolutionary theory of late-life mortality.

Aging↗

PubMedDate not supplied

Lifelong heterogeneity in fecundity is insufficient to explain late-life fecundity plateaus in Drosophila melanogaster.

Previous studies have demonstrated that fecundity, like mortality, plateaus at late ages in cohorts of Drosophila melanogaster. Although evolutionary theory can explain the decline and plateau in cohort fecundity at late ages, it is conceivable that lifelong heterogeneity in individual female fecundity is producing these plateaus. For example, consistently more fecund females may die at earlier ages, leaving only females that always laid a low number of eggs preponderant at later ages. We simulated fecundity within a cohort, assuming the two phenotypes described above, and tested these predictions by measuring age of death and age-specific fecundity for individual females from three large cohorts. We statistically tested whether there was enough lifelong heterogeneity in fecundity to produce a late-life plateau by testing whether early female fecundity could predict whether that female would live to lay eggs after the onset of the population fecundity plateau. Our results indicate that heterogeneity in fecundity is not lifelong and thus not likely to cause late-life fecundity plateaus. Because lifelong heterogeneity models for fecundity are based on the same underlying assumptions as heterogeneity models for late-life mortality rates, our test of this hypothesis is also an experimental test of lifelong heterogeneity models of late life generally.

Aging↗

PubMedDate not supplied

Aging, fertility, and immortality.

Evolutionary theory suggests that fecundity rates will plateau late in life in the same fashion as mortality rates. We demonstrate that late-life plateaus arise for fecundity in Drosophila melanogaster. The result qualitatively fits the evolutionary theory of late life based on the force of natural selection. But there are a number of alternative interpretations. Fecundity plateaus could be secondary consequences of mortality-rate plateaus. Female fecundity plateaus might arise from diminished male sexual function. Another alternative hypothesis is analogous to male sexual inadequacy: nutritional shortfalls. These may arise later in life because of a decline in female feeding or digestion. If some females have a life-long tendency to lay eggs at a faster rate, but die earlier, then aging for fecundity could arise from the progressive loss of the fast-layers, with the late-life plateau simply the laying patterns of individual females who were slow-layers throughout adult life. If this type of model is generally applicable to late life, then we should find that the females who survive to lay at a slow but steady rate in late life have a similar laying pattern in mid-life.

Aging↗

PubMedDate not supplied

The respiratory pattern in Drosophila melanogaster selected for desiccation resistance is not associated with the observed evolution of decreased locomotory activity.

We examined spontaneous locomotory behavior and respiratory pattern in replicate outbred populations of Drosophila melanogaster selected for desiccation resistance or starvation resistance, as well as their control and ancestral populations. Use of these populations allows us to compare evolved behavioral changes in response to different stress selections. We also reasoned that previously observed changes in respiratory patterns following selection for increased desiccation resistance might be associated with or even caused by changes in locomotory behavior. We measured spontaneous locomotory behavior using video recordings and a computer-based tracking system while simultaneously measuring patterns of CO(2) release from single fruit flies. Statistically significant differences in behavior were observed to be correlated with selection regime. Reduced levels of spontaneous locomotory activity were observed in moist air in both desiccation- and starvation-selected populations compared with their controls. Interestingly, in dry air, only the desiccation-selected flies continue to show reduced spontaneous locomotory activity. No correlation was found between the level of locomotory activity of individual flies and the respiratory patterns of those flies, indicating that the reduced activity levels that have evolved in these flies did not directly cause the documented changes in their respiratory pattern.

Adaptation, Physiological↗