Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state.

ABSTRACT: We identified a mutation in the CRYGD gene (P23S) of the gamma-crystallin gene cluster that is associated with a polymorphic congenital cataract that occurs with frequency of approximately 0.3% in a human population. To gain insight into the molecular mechanism of the pathogenesis of gamma-crystallin isoforms, we undertook an evolutionary analysis of the available mammalian and newly obtained primate sequences of the gamma-crystallin genes. The cataract-associated serine at site 23 corresponds to the ancestral state, since it was found in CRYGD of a lower primate and all the surveyed nonprimate mammals. Crystallin proteins include two structurally similar domains, and substitutions in mammalian CRYGD protein at site 23 of the first domain were always associated with substitutions in the st

SUBMITTER: Plotnikova OV 

PROVIDER: S-EPMC1950927 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature