Gene sharing in lens and cornea: facts and implications

The major water-soluble proteins (crystallins) responsible for the optical properties of the cellular lenses of vertebrates and invertebrates are surprisingly diverse and often differ among species (i.e., are taxon-specific). Many crystallins are encoded by the identical gene specifying a stress protein or a metabolic enzyme which has non-refractive functions in numerous tissues. This double use of a distinct protein has been called gene sharing. Abundant expression of various metabolic enzymes also occurs in a taxon-specific manner in corneal epithelial cells, suggesting that gene sharing extends to this transparent tissue. It has been proposed that one of the most abundant corneal enzymes (aldehyde dehydrogenase class 3) may protect the eye by directly absorbing ultraviolet light, as well as by providing an enzymatic function. It also seems possible that the high expression of corneal enzymes (5-40% of the water-soluble proteins) may reduce scattering in the corneal epithelium by minimizing spatial fluctuations in refractive index as they do in the lens. Thus, gene sharing may be a widespread phenomenon encompassing the lens, cornea and probably other systems. Lens-preferred expression of crystallin genes is integrated in a complex developmental program utilizing in many cases Pax-6. The differential expression of alpha B-crystallin (a small heat shock protein) in different tissues involves the combinatorial use of both shared and lens-specific cis-control elements. Corneal-preferred gene expression appears to depend in part on induction by environmental influences. Among the implications of gene sharing are that gene duplication is not required for the evolution of a new protein phenotype, a change in gene regulation is sufficient, that proteins may be under more than one selective constraint, affecting their evolutionary clock, and that it would be prudent to consider the possibility that any given gene may have important, unrecognized roles when planning to implement gene therapy in the future.