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Genome-Wide Association Study Reveals the Genetic Basis of Diapause-Induced Lifespan Extension and Fecundity in Drosophila melanogaster


Core Concepts
Diapause, a dormancy program in response to adverse environments, involves complex genetic and neural mechanisms that regulate lifespan extension and reproductive capacity in Drosophila melanogaster.
Abstract

The authors conducted a genome-wide association study (GWAS) using the Drosophila Genetic Reference Panel (DGRP) to identify the genetic basis of diapause in Drosophila melanogaster. They quantified diapause by assessing the ability of flies to undergo 35 days of diapause, recover, and produce viable progeny, which is a more stringent test of diapause success compared to previous studies.

The GWAS revealed 546 genetic variants associated with post-diapause fecundity, encompassing 291 candidate diapause-associated genes. Many of these genes were previously implicated in diapause, while others were newly identified. Gene network analysis showed that the diapause-associated genes were primarily linked to neuronal and reproductive system development.

The authors further complemented the genetic analysis by identifying specific neurons required for successful diapause. They found that blocking neuronal transmission in olfactory receptor neurons and temperature-sensing neurons impaired recovery from diapause. Removing the antenna, which houses these sensory neurons, reduced diapause lifespan and post-diapause fecundity, suggesting the olfactory system plays a critical role in diapause.

RNAi knockdown experiments identified two neuronal genes, Dip-γ and Scribbler, as required during recovery for post-diapause fecundity. These findings provide insights into the molecular, cellular, and genetic basis of adult reproductive diapause in Drosophila.

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Stats
Pearson's correlation coefficient (r) between post-diapause and non-diapause fecundity is 0.5682. The coefficient of determination (R^2) between post-diapause and non-diapause fecundity is 0.3228. The GWAS identified 546 genetic variants associated with diapause fecundity, encompassing 291 candidate diapause-associated genes. 40 out of the 291 candidate genes had been previously associated with diapause. 89 genes were associated with more than one diapause-associated variant.
Quotes
"Diapause is a dormancy program that occurs in response to an adverse environment, followed by resumption of development and reproduction upon the return of favorable conditions." "Successful diapause occurs optimally at different developmental stages depending on the organism. In Drosophila species, the optimal stage is the newly-eclosed adult." "We found that blocking neuronal transmission in the Orco-expressing neurons decreased the post-diapause/non-diapause fecundity ratio, further implicating odor perception in successful diapause."

Deeper Inquiries

How do the diapause-associated genes identified in this study interact with the known hormonal regulators of diapause, such as insulin, juvenile hormone, and ecdysone?

The diapause-associated genes identified in this study likely interact with the known hormonal regulators of diapause, such as insulin, juvenile hormone (JH), and ecdysone, to coordinate the complex process of diapause. Insulin signaling has been implicated in regulating various aspects of diapause, including metabolism and reproduction. Genes associated with insulin signaling, such as the insulin receptor (InR), may play a role in sensing environmental cues and coordinating the physiological changes required for diapause entry and recovery. Juvenile hormone (JH) is another key hormonal regulator of diapause, influencing processes like metabolism and reproduction. The interaction between diapause-associated genes and JH signaling pathways may modulate the timing and duration of diapause, as well as the resumption of development and reproduction post-diapause. Specific genes identified in the GWAS, such as Dip-γ and Scribbler, may be involved in the regulation of JH signaling or downstream targets that mediate the effects of JH on diapause-related traits. Ecdysone, another important hormone in insect development, could also interact with diapause-associated genes to regulate the transition between diapause and active development. The genetic variants identified in the study may influence the sensitivity of cells to ecdysone signaling or modulate the downstream effects of ecdysone on processes like metamorphosis and reproduction. Overall, the diapause-associated genes identified in this study likely form a complex regulatory network with the known hormonal regulators of diapause, working together to orchestrate the physiological changes required for successful diapause entry, maintenance, and recovery.

What are the potential trade-offs between the genetic mechanisms that promote diapause entry and those that facilitate diapause recovery and post-diapause fecundity?

The genetic mechanisms that promote diapause entry and those that facilitate diapause recovery and post-diapause fecundity may involve trade-offs due to the complex nature of diapause regulation. Genes involved in diapause entry may prioritize survival and stress resistance over reproductive output. These genes may regulate processes like metabolic slowdown, reproductive arrest, and stress resilience to ensure the organism's survival during adverse conditions. However, these mechanisms may come at the cost of reduced immediate fecundity and reproductive potential. On the other hand, genes that facilitate diapause recovery and post-diapause fecundity may prioritize reproduction and growth once favorable conditions return. These genes may regulate the reactivation of development, resumption of reproductive processes, and optimization of fecundity to maximize the organism's fitness in the new environment. However, the activation of these mechanisms may divert resources away from stress resistance and longevity, potentially impacting the organism's overall resilience in challenging conditions. Therefore, there may be a trade-off between the genetic mechanisms that promote diapause entry, which focus on survival and stress tolerance, and those that facilitate diapause recovery and post-diapause fecundity, which prioritize reproduction and growth. Balancing these trade-offs is essential for the organism to successfully navigate the diapause program and adapt to changing environmental conditions.

Given the importance of the olfactory system in diapause, how might olfactory cues from the environment influence the initiation and termination of the diapause program in Drosophila?

The olfactory system plays a crucial role in diapause, influencing the initiation and termination of the diapause program in Drosophila through the detection of environmental cues. Olfactory cues from the environment can provide essential information that guides the decision-making processes related to diapause entry, maintenance, and recovery. During diapause initiation, olfactory cues such as temperature changes, humidity levels, and food availability may trigger the onset of diapause by signaling unfavorable conditions to the organism. Olfactory receptors in the antenna detect these environmental cues and transmit signals to the brain, where they are integrated with hormonal and neural inputs to initiate the diapause program. For example, changes in temperature sensed by specific olfactory neurons may activate downstream pathways that lead to the suppression of reproductive processes and the induction of dormancy. In contrast, during diapause recovery, olfactory cues indicating the return of favorable conditions, such as optimal temperature, food availability, and mating partners, can stimulate the termination of diapause and the resumption of development and reproduction. Olfactory receptor neurons may detect these cues and trigger signaling cascades that promote the exit from diapause, the reactivation of metabolic processes, and the restoration of reproductive functions. Overall, olfactory cues from the environment serve as important triggers for the initiation and termination of the diapause program in Drosophila, providing critical information that guides the organism's responses to changing environmental conditions and ensures its survival and reproductive success.
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