• The neutral theory of molecular evolution suggests that molecular evolution is mainly due to neutral drift. Alternatively, molecular evolution may be mainly driven by natural selection.

• Four main observations were originally interpreted in favor of the neutral theory: molecular evolution has a rapid rate, its rate has a clock-like constancy, it is more rapid in functionally less constrained parts of molecules, and natural populations are highly polymorphic.

• Kimura argued that the high rate of evolution, and the high degree of variability of proteins, would, if caused by natural selection, impose a high genetic load. Neutral drift, however, can drive high rates of evolution, and maintain high levels of variability, without imposing a genetic load.

• The constant rate of molecular evolution gives rise to a 'molecular clock'.

• Neutral drift should drive evolution at a stochastically constant rate; Kimura pointed to the contrast between uneven rates of morphological evolution and the constant rate of molecular evolution and argued that natural selection would not drive molecular evolution at a constant rate.

• The molecular clock for proteins ticks over according to absolute time rather than generational time. But for silent changes in DNA, lineages with shorter generation times probably evolve faster. Neutral drift should cause the molecular clock to run according to generational, not absolute, time.

• Selection can operate without producing impossible genetic loads, and Kimura's original case for the neutral theory is no longer convincing.

• The neutral theory explains the higher evolutionary rate of functionally less constrained regions of proteins by the greater chance that a mutation there will be neutral.

• Selectionists explain the higher evolutionary rate of functionally less constrained regions of proteins by the greater chance that a mutation there will be a small, rather than a large, change.

• Pseudogenes and silent changes in third codon positions may be relatively functionally unconstrained. These parts of the DNA evolve faster than do the first two positions in codons, and meaningful third base changes. Neutralists attribute this high rate of evolution to enhanced neutral drift.

• For amino acids encoded by more than one codon, there are consistent biases in the frequencies of the codons. Changes between the silent codons are therefore not completely unconstrained.

• The neutral theory predicts a positive relation between the degree of variability of a molecule and its rate of evolution.