Biased Polyphenism in Polydactylous Cats Carrying a Single Point Mutation: The Hemingway Model for Digit Novelty

Abstract

Point mutations in a cis-regulatory element of Sonic Hedgehog are frequently associated with preaxial polydactyly in humans, mice, and cats. The Hemingway mutant in the Maine Coon cat exhibits polyphenic effects of polydactyly that are not equally distributed. A statistical analysis of a comprehensive data base of Hemingway mutants reveals a biased and discontinuous distribution of extra digits. Further biases exist in the difference of effects in fore- versus hind-limbs and in left-right asymmetry. These non-equally distributed phenotypic effects cannot be explained by the point mutation alone. We propose a double mapping model, termed the Hemingway Model, to account for the biased distribution of supernumerary digits. The model is based on the random bistability of individual cells in the limb area affected by the mutation and on the application of the Central Limit Theorem. It proposes two kinds of mapping events that (a) transform a mutational effect of single additive changes into a continuous distribution, and (b) transform the continuous distribution into discrete character states via developmental threshold effects. The threshold widths for the occurrence of discrete extra digits are specified as units of standard deviations of the continuous variable. This makes it possible to specify the generation of empirical developmental variables (the liability of quantitative genetics) as a result of developmental parameters that give rise to biased morphological patterns and phenotypic novelty. © 2013 Springer Science+Business Media New York.