The Centenary of the One-Gene One-Enzyme Hypothesis

Extract

THE early history of mouse genetics has been recently described by Paigen (2003), but one episode in this history perhaps has not received sufficient recognition. In 1900, as soon as Mendel’s work was rediscovered, the French biologist Lucien Cuénot decided to see whether Mendel’s rules applied to animals as well as plants. After 2 years of work, he reported that the coat of wild mice contains two pigments, black and yellow, and that crosses between wild mice and albinos and then between the resulting hybrids showed that the absence of either pigment behaves like a Mendelian recessive (Cuénot 1902). Within a year, however, Cuénot had found that certain strains of albino mice that had black (or yellow) mice in their ancestry behaved in crosses as if their version of albino was dominant over color. This led him to what, in essence, was the one-gene one-enzyme hypothesis (Cuénot 1903).

Cuénot proposed that the two pigments are made from a common chromogène as the result of the action of two distinct enzymes (diastases, as they were sometimes called in those days). Using the word “mnémon” (Coutagne 1902) for the inherited entity that holds the memory of how to make something, Cuénot proposed that three kinds of mnémon are responsible for the formation of the chromogen and the two enzymes and that these mnémons are inherited in a Mendelian fashion. In this simple hypothesis, therefore, he was drawing a distinction between the genes that are inherited and the things that the genes determine. At the same time, he was firmly connecting the abstractions of Mendelian genetics to the more down-to-earth realism of biochemistry.