Gene sharing in lens and cornea: facts and implications

Abstract

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.

Evidence for Gelsolin as a Corneal Crystallin in Zebrafish

“…The abundance of these water-soluble proteins in the cytoplasm might minimize the concentration fluctuations responsible for light scattering and maintain the cellular refractive index compatible with corneal transparency. In mammals, ALDH3 and other enzymes may play this role (28). The high proportion (ϳ30%) of ALDH1 and TKT in the transparent keratocyes and the specific reduction in these putative enzyme-crystallins in the reflective keratocytes of the freezeinjured, hazy rabbit cornea also support the notion that the abundance of particular proteins is structurally important for cellular transparency in the cornea (27).…”

“…Previous investigations have shown that the corneal cells of vertebrates accumulate unexpectedly high concentrations of enzymes among their water-soluble proteins that differ among species (28). For example, ALDH3 (22,23), TKT (24), and isocitrate dehydrogenase (25) are present at considerably higher levels in the epithelial cells of mammalian corneas than would be ex- lanes 1-3), rosey barb (P. conconius) (lanes 4 -6), and tricolor shark (B. melanopterus) (lanes 7-9); 14 g of proteins were used as markers (M).…”

“…The taxon-specific accumulation of intracellular water-soluble proteins, often enzymes, in the cornea resembles the high concentration of crystallins and enzyme-crystallins of the eye lens (6 -8). This suggests that the abundant corneal proteins contribute structurally, like the crystallins in the lens, to the transparency and optical properties of the cells in the cornea (28).…”

“…For example, ALDH1 and TKT comprise ϳ30% of the water-soluble protein of the transparent keratocytes of the rabbit cornea, whereas this value is markedly reduced in the reflective keratocytes after freeze injury. It thus appears that corneal cells, like lens cells, accumulate certain multifunctional, water-soluble proteins that contribute structurally to their optical properties as well as having other non-refractive roles (28).…”

Existence of Unprocessed a Mitochondrial Enzyme: YDL178wp in the Membrane Fraction as an Oligomeric Formation with a Protein-Unfolding Activity

“…Meanwhile, S-form exhibited smaller sized molecule as a mitochondrial mature protein, which is processed mitochondrial presequence region at the site of N-terminal amino acids Y36 and S37. These results exhibited that YDL178wp belongs to the proteins known as "protein moonlighting"; one gene product has various functions with alternative localization [8,9].…”