The evolution of ATP synthase is thought to have been modular whereby two functionally independent subunits became associated and gained new functionality. This association appears to have occurred early in evolutionary history, because essentially the same structure and activity of ATP synthase enzymes are present in all kingdoms of life. The F-ATP synthase displays high functional and mechanistic similarity to the V-ATPase. However, whereas the F-ATP synthase generates ATP by utilising a proton gradient, the V-ATPase generates a proton gradient at the expense of ATP, generating pH values of as low as 1.
The F region also shows significant similarity to hexameric DNA helicases (especially the Rho factor), and the entire enzyme region shows some similarity to -powered T3SS or flagellar motor complexes. The αβ hexamer of the F region shows significant structural similarity to hexameric DNA helicases; both form a ring with 3-fold rotational symmetry with a central pore. Both have roles dependent on the relative rotation of a macromolecule within the pore; the DNA helicases use the helical shape of DNA to drive their motion along the DNA molecule and to detect supercoiling, whereas the αβ hexamer uses the conformational changes through the rotation of the γ subunit to drive an enzymatic reaction.
The  motor of the F particle shows great functional similarity to the  motors that drive flagella. Both feature a ring of many small alpha-helical proteins that rotate relative to nearby stationary proteins, using a  potential gradient as an energy source. This link is tenuous, however, as the overall structure of flagellar motors is far more complex than that of the F particle and the ring with about 30 rotating proteins is far larger than the 10, 11, or 14 helical proteins in the F complex. More recent structural data do however show that the ring and the stalk are structurally similar to the F particle.
The modular evolution theory for the origin of ATP synthase suggests that two subunits with independent function, a DNA helicase with ATPase activity and a  motor, were able to bind, and the rotation of the motor drove the ATPase activity of the helicase in reverse. This complex then evolved greater efficiency and eventually developed into today's intricate ATP synthases. Alternatively, the DNA helicase/ motor complex may have had  pump activity with the ATPase activity of the helicase driving the  motor in reverse. This may have evolved to carry out the reverse reaction and act as an ATP synthase.