Genome-wide analysis of long-term evolutionary domestication in Drosophila melanogaster.

Experimental evolutionary genomics now allows biologists to test fundamental theories concerning the genetic basis of adaptation. We have conducted one of the longest laboratory evolution experiments with any sexually-reproducing metazoan, Drosophila melanogaster. We used next-generation resequencing data from this experiment to examine genome-wide patterns of genetic variation over an evolutionary time-scale that approaches 1,000 generations. We also compared measures of variation within and differentiation between our populations to simulations based on a variety of evolutionary scenarios. Our analysis yielded no clear evidence of hard selective sweeps, whereby natural selection acts to increase the frequency of a newly-arising mutation in a population until it becomes fixed. We do find evidence for selection acting on standing genetic variation, as independent replicate populations exhibit similar population-genetic dynamics, without obvious fixation of candidate alleles under selection. A hidden-Markov model test for selection also found widespread evidence for selection. We found more genetic variation genome-wide, and less differentiation between replicate populations genome-wide, than arose in any of our simulated evolutionary scenarios.

Herbal supplement extends life span under some environmental conditions and boosts stress resistance.

Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span.

Long-term functional side-effects of stimulants and sedatives in Drosophila melanogaster.

BACKGROUND: Small invertebrate animals, such as nematodes and fruit flies, are increasingly being used to test candidate drugs both for specific therapeutic purposes and for long-term health effects. Some of the protocols used in these experiments feature such experimental design features as lifelong virginity and very low densities. By contrast, the ability of both fruit flies and nematodes to resist stress is frequently correlated with their longevity and other functional measures, suggesting that low-stress assays are not necessarily the only useful protocol for testing the long-term effects of drugs. METHODOLOGY/PRINCIPAL FINDINGS: Here we report an alternative protocol for fruit fly drug-testing that maximizes reproductive opportunities and other types of interaction, with moderately high population densities. We validate this protocol using two types of experimental tests: 1. We show that this protocol detects previously well-established genetic differences between outbred fruit fly populations. 2. We show that this protocol is able to distinguish among the long-term effects of similar types of drugs within two broad categories, stimulants and tranquilizers. CONCLUSIONS: Large-scale fly drug testing can be conducted using mixed-sex high-density cage assays. We find that the commonly-used stimulants caffeine and theobromine differ dramatically in their chronic functional effects, theobromine being more benign. Likewise, we find that two generic pharmaceutical tranquilizers, lithium carbonate and valproic acid, differ dramatically in their chronic effects, lithium being more benign. However, these findings do not necessarily apply to human subjects, and we thus do not recommend the use of any one substance over any other.