Abstract. Eukaryotes arose just once in 4 billion years of evolution, from a singular endosymbiosis between an archaeal host cell and a bacterial endosymbiont, which ultimately evolved into mitochondria. Loss of genes from mitochondria enabled a massive expansion in nuclear genome size and gene expression, giving eukaryotes 3-5 orders of magnitude more energy per gene than prokaryotes. Mitochondria capable of oxidative phosphorylation always retain a core bioenergetic genome, which seems to be necessary to support this massively expanded nuclear genome. The mechanisms of selection on the mitochondrial genome are distinct from those on nuclear genes, involving uniparental inheritance rather than sexual recombination. The evolution of the germline in bilaterians relates largely to selection for mitochondrial function, including early sequestration of large oocytes containing thousands of mitochondria.