Geranylgeranyltransferase I controls the function of a variety of cellular proteins by attaching a geranylgeranyl group to the carboxy-terminus of proteins. The purified enzyme from rat brain is comprised of two polypeptides, a catalytic α-subunit (GGTα) and a substrate-binding β-subunit (GGTβ). The present paper demonstrates the existence of a GGTβ multigene family in humans by describing the presence and characterization of at least 13 pseudogenes related to this protein. Sequencing: of numerous PCR-derived clones, obtained following amplification of human genomic DNA, revealed multiple, distinct but highly related sequences. All clones had a common deletion of 99-bp that conforms to the GT-AG rule of splicing in eukaryotes, and differed from the human GGTβ cDNA sequence by multiple nucleotide substitutions. PCR amplification from mRNA, however, yielded only the sequence expected for the expressed GGTβ protein. This apparent paradox was resolved by cloning and sequencing a complete GGTβ-specific pseudogene. Multiple features of the cloned gene, in particular the absence of introns, presence of flanking direct repeats, and the lack of sequence similarity with the untranscribed region of the gene, indicate that this clone represents a processed pseudogene possibly resulting from a mis-spliced transcript. Multiple GGTβ-specific pseudogenes appear to have resulted from more than one retroposition event. These results suggest a potential role for mis-splicing in the evolutionary diversity of pseudogenes.
- Geranylgeranyltransferase I β-subunit
- Molecular evolution
- Multigene family
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