Characterization and evolution of the expressed rat ferritin light subunit gene and its pseudogene family. Conservation of sequences within noncoding regions of ferritin genes

The iron storage protein ferritin consists of two types of subunits of different molecular weight, heavy (H) and light (L). The rat genome contains approximately 20 copies of the ferritin L-subunit gene, of which we have sequenced seven. One is an expressed ferritin gene containing three introns located between the alpha-helical domains of the L-subunit protein. The remaining six have the characteristics of processed pseudogenes. Sequence divergence suggest that these pseudogenes arose approximately 3-12 × 10(6) years ago, well within the 30 × 10(6) years of divergence of rat and mouse. By using intron probes derived from the expressed ferritin L-gene, a homologous second copy has been identified in some Fischer rats. Comparison of the 5'-untranslated region of the rat L-gene with the published sequences of this region of the human L (Santoro, C., Marone, M., Ferrone, M., Costanzo, F., Colombo, M., Minganti, C., Cortese, R., and Silengo, L. (1986) Nucleic Acids Res. 14, 2863-2876) and H (Costanzo, F., Colombo, M., Staempfli, S., Santoro, C., Marone, M., Frank, R., Delius, H., and Cortese, R. (1986) Nucleic Acids Res. 14, 721-735) genes and of a bullfrog cDNA (Didsbury, J. R., Theil, E. C., Kaufman, R. E., and Dickey, L. F. (1986) J. Biol. Chem. 261, 949-955) show a strongly conserved 28-base pair sequence, suggesting a translational regulatory function. The 5' flanking region of the rat L-gene contains sequences homologous to those in the flanking areas of the human L- and H-genes. The implications of these conserved sequences for control of ferritin expression are discussed.