Molecular characterization of rat multigene family encoding proline-rich proteins

Three members of the rat proline-rich protein multigene family have been characterized. Each of these genes, RP4, RP13, and RP15, contains three exons and they are approximately 4.8, 5.7, and 5.4 kb, respectively. The DAN sequences of RP4 and RP13 are greater than 93% homologous in the 3.1-kb segment extending from the 5'-upstream region (approximately nucleotide -930) to 238 nucleotides after the second exon/intron junction; however, regions further downstream, intron II and exon III, share less than 43% identity. In contrast, exon III from RP15, RP13, and the previously sequenced mouse PRP gene MP2 are more than 73% conserved. These analyses suggest that the duplication of the ancestral genes to RP13 and RP4 occurred prior to the divergence of the rat PRP genes. The results also indicate that in the past 21.5 million years, multiple recombination events have resulted in a very high degree of divergence among intron II and exon III of RP4 and RP13. This divergence is due in part to the insertion of members of the rat long interspersed repeat DNA family at -930 bp upstream from the transcription initiation site and within intron II of RP13. Comparisons of the nucleotide sequences and organization of exon I with the genomic organization of PRP and glutamic acid/glutamine-rich protein genes in this and previous studies reveal striking resemblance among these genes. These observations are consistent with the notion that this super multigene family arose from duplication of progenitor genes via unequal crossing over events. In addition, the results suggest that concerted evolution has occurred within the tandemly repeated motif of exon II.