Human Lens γ -crystallins: Isolation, Identification, and Characterization of the Expressed Gene Products

We have isolated the individual γ -crystallins expressed in young human lenses and identified with which of the six known human γ -crystallin genes they each correspond. We find that at least 90% of the γ -crystallins synthesized in the young human lens are the products of genes γ G3 and γ G4. We demonstrate that γ G4-crystallin undergoes a temperature-dependent phase separation, and we have measured the low-concentration branch of its coexistence curve (phase separation temperature vs. concentration) up to about 40 mg/ml. By comparison, we found no evidence of γ G3-crystallin phase separating, even at lower temperatures and higher concentrations. This is consistent with predictions based on sequence homology between human and rat γ -crystallins. The implications of these findings for human inherited and senile cataracts are considered.