Causes and consequences of genetic variation in fitness

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Evolutionary Biology is undergoing radical transformation as its embrace extends ever further into the workings of the organism, the cell, and the genome. More and more, the genome appears to be not simply a well-ordered blueprint but a noisy 'parliament' of interacting genes. My research team studies the origins and nature of genetic variation using original and powerful techniques in the ordinary fruit fly, Drosophila. Our research has shown that levels of genetic variation related to survival and lifetime reproductive success are surprisingly high, given that these are the very components of Darwinian fitness. The proposed research uses special cloning methods to quantify three distinct sources of variation: spontaneous mutation, gene-gene interactions, and sexually antagonistic genes. First, we will suspend natural selection across the entire genome, allowing mutations to accumulate unchecked over many generations. Preliminary results show that mutations manifest themselves quickly, and the same mutations have a much more severe impact on males than females. Experiments will measure genetic variation in fitness over the full lifespan of the fly. We will characterize growth, reproduction, ageing and death in our lines, and investigate the controversial phenomenon of 'plateaus in senescence', in which ageing appears to stop late in life. Next, we will break apart the cloned genomes and assemble new mixtures to study the degree to which genes add together in effect or interact synergistically. Finally, in all experiments, we will measure the consistency of genetic effects in the two sexes and analyze for sexually antagonistic genes. Our research has implicated SA genes in reducing the average fitness of both females and males. This research is modular and scalable, facilitating the training of expert personnel at every level. It explores fundamental questions in evolutionary genetics, and ultimately provides insight into problems as diverse as genetic diseases, infertility, and senescence. By showing how fitness is governed in bottled flies, we hope to illuminate the workings of other genomes, notably our own, and shape understanding of a central question in Biology: why so much fitness-related variation?