title: The role of macromolecular crowding in the evolution of lens crystallins with high molecular refractive index.
abstract: Crystallins are present in the lens at extremely high concentrations in order to provide transparency and generate a high refractive power of the lens. The crystallin families prevalent in the highest density lens tissues are γ-crystallins in vertebrates and S-crystallins in cephalopods. As shown elsewhere, in parallel evolution, both have evolved molecular refractive index increments 5-10% above those of most proteins. Although this is a small increase, it is statistically very significant and can be achieved only by very unusual amino acid compositions. In contrast, such a molecular adaptation to aid in the refractive function of the lens did not occur in crystallins that are preferentially located in lower density lens tissues, such as vertebrate α-crystallin and taxon-specific crystallins. In the current work, we apply a model of non-interacting hard spheres to examine the thermodynamic contributions of volume exclusion at lenticular protein concentrations. We show that the small concentration decrease afforded by the higher molecular refractive index increment of crystallins can amplify nonlinearly to produce order of magnitude differences in chemical activities, and lead to reduced osmotic pressure and the reduced propensity for protein aggregation. Quantitatively, this amplification sets in only at protein concentrations as high as those found in hard lenses or the nucleus of soft lenses, in good correspondence to the observed crystallin properties in different tissues and different species. This suggests that volume exclusion effects provide the evolutionary driving force for the unusual refractive properties and the unusual amino acid compositions of γ-crystallins and S-crystallins.
authors.affiliation: Dynamics of Macromolecular Assembly Section, Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Huaying
authors.initials: H
authors.lastname: Zhao
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Magone
authors.forename: Peter
authors.initials: P
authors.lastname: Schuck
mesh_terms: D000818:Animals; D003459:Crystallins / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009997:Osmotic Pressure; D012031:Refractometry; D013816:Thermodynamics
chemical_list: D003459:Crystallins