NIH Grants of the Pletcher Lab

Pletcher, Scott D.    Promislow, Daniel Edward Lee   

University of Michigan Ann Arbor, Ann Arbor, MI, & University of Washington, United States, respectively

Abstract

Fitness trade-offs are thought to play a fundamental role in the genetic architecture of fitness traits, including shaping genes relevant to human health. Reproductive costs, particularly those that influence lifespan and late-age disease, have been explored at the phenotypic and population genetic levels in a wide range of species, but little is known about their underlying biological mechanisms. In our work on the fruit fly, Drosophila melanogaster, we have found that survival costs of reproduction are mediated by evolutionarily conserved neuropeptides, that these peptides are dynamically controlled by neural circuits that influence reproductive success, and that these circuits influence downstream metabolic networks. The goal of our proposed research is to identify and characterize conserved neural signaling pathways that orchestrate the control of costs of reproduction and influence their evolution. We propose a model whereby an individual?s reproductive strategy, with its attendant effects on aging, is determined by neurological decisions in response to a combination of that individual?s reproductive expectation and reproductive achievement. Importantly, these decisions are independent of any physical or energetic effects associated with mating itself. We will test this model using innovative approaches to identify the environmental cues and perceptive systems underlying reproductive expectation and reward, as well as the signaling pathways that are influenced by these processes. We will combine a reductionist approach, using single-gene mutations and advanced cell-biology techniques for neuronal manipulations, with a systems and network biology approach to identify mechanisms underlying reproduction and aging. When complete, this research will provide new insights into the cues that portend reproductive success, the mechanisms through which those cues are interpreted, and their regulatory effects on lifespan. These insights will aid our understanding of quintessential evolutionary and health issues ? including sexual conflict, reproductive investment, and aging.

Public Health Relevance

Reproductive trade-offs?the idea that the fitness benefits of reproduction come at a cost to other fitness traits, particularly aging?are thought to play a central role in natural variation and human health, but little is known about their underlying biological mechanisms. The research proposed here aims to identify and characterize conserved neural signaling pathways that mediate the proximate and evolutionary mechanisms underlying survival costs of reproduction. Our findings will inform our understanding of fundamental evolutionary and health issues, including sexual conflict, reproductive investment, and aging.