Crystallins make up the bulk of the lens and are responsible for refracting and focusing light onto the retina. Many proteins in the cell have properties (high solubility, proper refractive index, etc.) suitable for lens function, and a wide variety of such proteins have been co-opted during evolution for use in the lens. For example, the α crystallins (top two lines) are closely related to heat shock proteins and are found in all vertebrate lenses. In contrast, δ crystallin (third line) is closely related to an enzyme involved in amino acid metabolism and is found only in birds and reptiles. The three crystallin gene control regions shown are a patchwork of different regulatory sequences that reflect the evolutionary history of each gene. The common feature of all three control regions is the presence of binding sites for the gene regulatory protein Pax6. Pax6 is the vertebrate homolog of the fly Toy and Eyeless proteins (see Figure 7-75) and is one of the key regulators that specifies eye development. Proteins above each gene control region are transcriptional activators and those below the line are repressors. (Adapted from E.H. Davidson, Genomic Regulatory Systems: Development and Evolution, pp. 191–201. San Diego: Academic Press, 2001 and A. Cvekl and J. Piatigarsky, BioEssays 18:621–630, 1996.)