The theory of evolution by natural selection, as first proposed by Darwin (1859) and Wallace (1871), is centered on the idea that individual organisms differ in fitness which makes them more or less likely to contribute offspring, and likewise alleles, to the next generation. In this context, fitness is defined by an individual’s ability to survive and produce viable offspring. Two traits intimately connected to fitness are fecundity and life span. These traits are complex quantitative traits that exhibit extensive natural variation due to a combination of the effects of many genes and environmental factors (life span: Maynard Smith, 1958; Rose and Charlesworth, 1981a; Rose, 1984; Brown-Borg et al., 1996; Nuzhdin et al., 1997; Kimura et al., 1997; Finch and Tanzi, 1997; Shook and Johnson, 1999; Guarente and Kenyon, 2000; Zou et al., 2000; Fabrizio et al., 2001; Clancy et al., 2001; Leips and Mackay, 2000; 2002; Blüher et al., 2003; Geiger-Thornsberry and Mackay, 2004; Kapahi et al., 2004) (fecundity: (Rose and Charlesworth, 1981a, b; Tatar et al., 1996; Sgro and Hoffmann, 1998; Tzolovsky et al., 1999; Terashima and Bownes, 2004; Leips et al., 2006). An important source of environmental variation affecting these traits is resource quality and availability (Chapman and Partridge, 1996; Lee et al., 1999; Lin et al., 2000; Good and Tatar, 2001; Pletcher et al., 2002; Terashima and Bownes, 2004; Skorupa et al., 2008). Specifically, we know that dietary restriction extends life span in a number of species (Lee et al., 1999; Lin et al., 2000; Pletcher et al., 2002; Tu and Tatar, 2003; Bishop and Guarente, 2007), and often results in a decline in fecundity (Rose and Charlesworth, 1981a, b; Kirkwood and Rose, 1991; Leips et al., 2006). As demonstrated by the response to dietary restriction, the ability of one genotype to express multiple phenotypic values in response to a single, directional, repeatable change in a single environmental cue is known as phenotypic plasticity (Bradshaw, 1965; Travis, 1994). Many organisms exhibit plasticity in order to thrive in multiple environments, rather than being restricted to one environment. Phenotypic plasticity is especially advantageous in cases of heterogenous environments, seasonal variations, and differences in resource availability (Bradshaw, 1965; Travis, 1994).

Although it is clear that life span and age-specific fecundity are genetically controlled, the specific genes influencing natural variation in these traits, their plastic response to the dietary environment, and their relationship with each other are largely unknown.Many studies indicate that genes in the insulin signaling pathway are involved in the response to dietary restriction (Clancy et al., 2001; Tatar et al., 2001; Kapahi et al., 2004), and artificial mutations in many genes in this pathway extend life span in a number of organisms (Tu and Tatar, 2003; Fabrizio et al., 2001; Kimura et al., 1997; Bluher et al, 2003). What is not known is what specific genes contribute to the natural variation in fecundity and life span and their plastic response to the dietary environment.

The goal of my project is to identify genes influencing life span, age-specific fecundity, and plasticity to diet in these two traits. To do this I have associated phenotypic variation with variation in DNA sequence to uncover potential candidate genes affecting these traits and their plastic response to different diets.

The genetic lines I have used in this study are part of a Drosophila community resource known as the Drosophila Genome Reference Panel (DGRP) for which 192 lines have been fully sequenced by Baylor College of Medicine. Sequence information for approximately 2.5 million single nucleotide polymorphisms (SNPs) will soon be publicly available for genome wide association studies (GWAS) using phenotype values for these lines acquired by the database users to identify candidate genes involved in the trait under investigation (Mackay et al. 2008).  Our collaborator, Michael Magwire (NC State) is involved in the development of this database and has graciously completed the GWAS for the phenotypes I assayed and submitted.

In order to assess the role of dietary restriction on lifespan and age-specific fecundity, I completed the experiment using flies reared as adults on either a high yeast (HY) diet or a low yeast (LY) diet. Yeast is the primary protein and nutrition source for adult flies in nature. These two diets were chosen from the 25 diets assayed in the Skorupa et al., (2008) study because they showed the largest difference in trait values for the lines used in their study and this combination of dietary component concentrations is practical to handle in the lab. The diets are sucrose based standard lab media consisting of sucrose, agar, water, yeast, and preservatives. They are identical in concentrations of all components except yeast. The HY diet contains 20% yeast while the LY diet contains 5% yeast.