The analysis of the developmental pattern of the aA-, aB-, PSI-, PB2-, ,GB3-, PA3/A1-, and ps-crystallin genes during fetal and postnatal development of the rat shows that the differential regulation of crystallin synthesis relies on differential gene shutdown rather than differential gene activation; that is, all crystallin genes are active during early development but turn off at different stages. The only two exceptions to this rule are the aB-and pscrystallin genes. The aB-crystallin gene transcript becomes first detectable at 18 days of fetal development, while the ps-crystallin gene appears to be active only in the postnatal period.We also determined the absolute numbers of the aA-, aB-, BBl-, pB2-, PB3-, PA3/A1-, ps-, and y-crystallin gene transcripts present in the lens at various times after birth. Comparison of these RNA data with the published protein data shows that the aB-and flB2-crystallin RNAs are relatively overrepresented, suggesting the possibility that these two RNA species are not used as efficiently as other crystallin mRNAs. Examination of the known (hamster) aB-crystallin sequence and elucidation of the (rat) PB2-crystallin sequence yielded no evidence for aberrant codon usage. These two RNAs have one sequence motif in common: they are the only crystallin mRNAs in which the translation initiation codon is preceded by CCACC.The abundant water-soluble proteins of the mammalian lens are encoded by three gene families, the a-, p-and ycrystallin gene families (for review see [l, 21). The a-crystallin gene family has only two members, the aA-and aB-crystallin genes. The protein products of these two genes form the large a-crystallin complex. The p-crystallin gene family is known to have at least six members, of which only four, namely PA3/1-, the PBl-, the BB2-, and the pB3-crystallin sequences, have been cloned. The ,!I-crystallins are found as hetero-oligomers in the lens. The third crystallin gene family, the y-crystallin genes, is evolutionarily related to the fi-crystallin gene family. In the rat the y-crystallin gene family has seven members. Six of these are closely related and encode the monomeric ycrystallins. The seventh codes for the more distantly related monomeric ps-crystallin (for review, see [3]). It has been previously shown that the six y-crystallin genes are all turned on during the early embryonic development of the rat or mouse lens but are differentially shut off during postnatal development [4, 51. As the y-crystallins and the P-crystallins derive from the same ancestral sequence, it is of interest to determine whether the developmental expression of the p-crystallin genes follows the same pattern as that of the y-crystallin genes. If so, these two gene families might have inherited the same mechanism of gene activation. We show that the all members of these two gene Families, except for the ps-crystallin gene, are indeed activated during early embryonic development of the rat lens. We further show that the activation of the aBcrystallin gene lags behind that of the aA-cr...