Haldane's dilemma

Haldane's dilemma, also known as the waiting time problem,^[1] is a limit on the speed of beneficial evolution, calculated by J. B. S. Haldane in 1957. Before the invention of DNA sequencing technologies, it was not known how much polymorphism DNA harbored, although alloenzymes (variant forms of an enzyme which differ structurally but not functionally from other alloenzymes coded for by different alleles at the same locus) were beginning to make it clear that substantial polymorphism existed. This was puzzling because the amount of polymorphism known to exist seemed to exceed the theoretical limits that Haldane calculated, that is, the limits imposed if polymorphisms present in the population generally influence an organism's fitness. Motoo Kimura's landmark paper on neutral theory in 1968^[2] built on Haldane's work to suggest that most molecular evolution is neutral, resolving the dilemma. Although neutral evolution remains the consensus theory among modern biologists,^[3] and thus Kimura's resolution of Haldane's dilemma is widely regarded as correct, some biologists argue that adaptive evolution explains a large fraction of substitutions in protein coding sequence,^[4] and they propose alternative solutions to Haldane's dilemma.