My project will investigate the interactions between the mitochondrial and nuclear genomes. Proteins encoded by both genomes are required for cell respiration, the main source of energy production in eukaryotes. Selection is strong for optimal function of cell respiration, leading to coadaptation of mitochondrial and nuclear genes (“cytonuclear coevolution”). Experiments have show that the breakup of such coadapted gene complexes can lead to hybrid breakdown, which may reduce gene flow between populations and generate reproductive isolation. Hence, cytonuclear coevolution can be important in generating intraspecific genetic diversity. I will use a threefold approach to evaluate the importance of cytonuclear coevolution in natural populations, using a hybrid zone in the black-tailed brush lizard as a model system. Firstly, I will investigate cytonuclear coadaptation at the nucleotide level by studying sequence variation in interacting genes within and between hybridizing populations. Secondly, I will study the fitness consequences of cytonuclear coevolution by comparing enzyme activity of coadapted versus maladaptive gene products. Finally, I will evaluate the potential for cytonuclear coevolution to generate reproductive isolation by using single nucleotide polymorphisms (SNPs) and nuclear intron sequences to evaluate nuclear genomic divergence. This research will provide a fundamental contribution to understanding reproductive isolation and genetic diversity in natural populations.