Connecting genotype to phenotype: drosophila simulans mitochondria as a model

The influence of genotype variation on phenotype has been a longstanding question in biology but it is now one of the greatest challenges of the post-genomics era. Discovering the link between common gene variants that affect phenotypes within and between populations is likely to provide insight into the molecular physiology of phenotypic traits and the mechanisms by which they evolve. The overall goal of this thesis is to link naturally occurring genotypic variation with the organism’s phenotype. The specific goal of this thesis is to connect natural variation in the mitochondrial genotype with the organismal phenotype using the model organism Drosophila simulans.Mitochondria are intracellular organelles found in most eukaryotes and produce over 90% of the energy needed by cells. Determining the connection of mitochondrial genotype to whole organism phenotype is of particular interest because of the broad use of mitochondrial (mt) DNA as a molecular marker in evolutionary biology and population genetics, the organelle’s central role in cellular energy production, the potential for the mitochondria to influence organismal distribution particularly in the face of climate change and in human degenerative disease. I use the model organism D. simulans because it has high genetic variability, can be easily sampled from the wild and manipulated in the lab, and the energy producing reactions that take place in its mitochondria are highly conserved among metazoa. I studied naturally occurring mutations to understand the influence of these changes in natural populations.The four studies in this thesis have employed a Genotype-Biochemistry-Phenotype (GBP) model to link naturally occurring variation in the mitochondrial genotype with organism phenotype in D. simulans mitochondria. Three major conclusions can be drawn from the thesis that follow the genotype to biochemistry to phenotype model. Firstly, a subset of the mutations in genes that comprise the mitochondrial genotype is functionally significant. Secondly, the biochemical efficiency of OXPHOS is regulated by mitochondrial homeostasis. Thirdly, key organismal life history traits influenced by the mitochondrial genotype and this is mediated through the biochemistry of OXPHOS