The role of relaxed natural selection against colorblindness in producing extreme variation in X-chromosome photopigment gene number and sequence among individuals with normal color vision

Abstract

Tandem genes on the X-chromosome encode the L and M pigments underlying red-green color vision. Surprisingly, among individuals with normal color vision, the L and M genes are extremely polymorphic. We hypothesize that the polymorphism was produced by repeated rounds of unequal homologous recombination that alternately generated gene arrangements associated with colorblindness, and then rescued the colorblind gene array by recombination with a normal array in a subsequent generation. When colorblind arrays recombine with normal arrays, M gene sequences can be introduced into the L genes of arrays that will confer normal color vision, creating variation. Our hypothesis predicts that an increase in the number of colorblind arrays in the gene pool will, in turn, increase the proportion of L genes specifying alanine at position 180, which is specific to the M gene of all non-human primates. We tested these predictions by comparing the proportions of arrays having only 2 genes and of L genes encoding alanine at position 180 for several human groups that differ in incidence of colorblindness. The groups differed significantly in the proportion of arrays with just 2 genes and the proportion of L genes that specified alanine at position 180, both of which were strongly correlated with the incidence of colorblindness (r2=0.66 and 0.77 respectively). Traditionally, maintenance of genetic polymorphism within a population been thought to require a selective advantage. In contrast, the results suggest that extreme normal polymorphism in the L and M genes is produced by the opposite—a relaxation of selection.

Footnotes

 Supported by NIH EY09303 and EY09620.