scholarly journals Combining metabolomics and experimental evolution reveals key mechanisms underlying longevity differences in laboratory evolved Drosophila melanogaster populations

2021 ◽  
Author(s):  
Mark Phillips ◽  
Kenneth R. Arnold ◽  
Zer Vue ◽  
Heather Beasley ◽  
Edgar Garza Lopez ◽  
...  

Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution study the genetic basis of longevity itself. Here we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD+ and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results in total provide very plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits like aging.

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 52 ◽  
Author(s):  
Federica De Lazzari ◽  
Federica Sandrelli ◽  
Alexander J. Whitworth ◽  
Marco Bisaglia

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson’s disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal’s rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments.


2015 ◽  
Vol 186 (5) ◽  
pp. 582-593 ◽  
Author(s):  
Vanessa Kellermann ◽  
Ary A. Hoffmann ◽  
Torsten Nygaard Kristensen ◽  
Neda Nasiri Moghadam ◽  
Volker Loeschcke

Oecologia ◽  
2009 ◽  
Vol 161 (4) ◽  
pp. 781-790 ◽  
Author(s):  
Susanne Wölfle ◽  
Monika Trienens ◽  
Marko Rohlfs

2015 ◽  
Vol 197 (23) ◽  
pp. 3676-3685 ◽  
Author(s):  
Anne K. Dunn ◽  
Bethany A. Rader ◽  
Eric V. Stabb ◽  
Mark J. Mandel

ABSTRACTBacterial bioluminescence is taxonomically restricted to certain proteobacteria, many of which belong to theVibrionaceae. In the most well-studied cases, pheromone signaling plays a key role in regulation of light production. However, previous reports have indicated that certainPhotobacteriumstrains do not use this regulatory method for controlling luminescence. In this study, we combined genome sequencing with genetic approaches to characterize the regulation of luminescence inPhotobacterium leiognathistrain KNH6, an extremely bright isolate. Using transposon mutagenesis and screening for decreased luminescence, we identified insertions in genes encoding components necessary for the luciferase reaction (lux,lum, andriboperons) as well as in nine other loci. These additional loci encode gene products predicted to be involved in the tricarboxylic acid (TCA) cycle, DNA and RNA metabolism, transcriptional regulation, and the synthesis of cytochromec, peptidoglycan, and fatty acids. The mutagenesis screen did not identify any mutants with disruptions of predicted pheromone-related loci. Using targeted gene insertional disruptions, we demonstrate that under the growth conditions tested, luminescence levels do not appear to be controlled through canonical pheromone signaling systems in this strain.IMPORTANCEDespite the long-standing interest in luminous bacteria, outside a few model organisms, little is known about the regulation and function of luminescence. Light-producing marine bacteria are widely distributed and have diverse lifestyles, suggesting that the control and significance of luminescence may be similarly diverse. In this study, we apply genetic tools to the study of regulation of light production in the extremely bright isolatePhotobacterium leiognathiKNH6. Our results suggest an unusual lack of canonical pheromone-mediated control of luminescence and contribute to a better understanding of alternative strategies for regulation of a key bacterial behavior. These experiments lay the groundwork for further study of the regulation and role of bioluminescence inP. leiognathi.


1984 ◽  
Vol 4 (5) ◽  
pp. 387-396 ◽  
Author(s):  
Carmen Arribas ◽  
Marta Izquierdo

We have studied the presence of a cloned fragment of DNA from Drosophila melanogaster in other organisms by means of nucleic acid hybridization analysis. The isolated region is localized in polytene chromosomes at the 63F subdivision. This region includes a puff that responds within minutes to ecdysone stimulation. We have found that 63F DNA from D. melanogaster hybridizes ‘in situ’ to both DNA and RNA from D. simulans, D. teissieri, and D. hydei. In all these species the isolated DNA remains associated with one early-ecdysone stimulated puff. The isolated Drosophila recombinant DNA is also complementary to polyadenylated RNA from foetal and adult rat liver but fails to hybridize to the nonpolyadenylated RNA classes from both sources and to polyadenylated RNA from rat mammary glands.


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