Life's first billions of years passed with a single grade of simple cells (bacteria and archaea). Then a qualitative threshold was crossed: a host cell, instead of digesting another energy-producing bacterium, kept it alive inside. Over time this internalized partner became the cell's power plant (the mitochondrion); in plants, photosynthesizing chloroplasts were acquired the same way. The evidence for this "endosymbiosis" is concrete: mitochondria and chloroplasts carry their own DNA and divide much as bacteria do.

The eukaryotic cell differs from its predecessors by enclosing its genetic material in a membrane-bound nucleus and partitioning itself into internal compartments. This internal order made far larger genomes and complex regulation possible.

When eukaryotes first appeared is debated; molecular clocks and contested fossil traces point to somewhere between 1.6 and 2.1 billion years ago. What is clear is that this cell type did not stay solitary: the nucleated cell was the structural leap that later made multicellularity — and therefore fungi, plants, and animals — possible.