Pseudogenes

Pseudogenes generated via a messenger RNA (mRNA) intermediate demonstrate the features of processed RNA. These genes lack the flanking transcriptional regulatory sequences, do not contain introns, and typically have a polyadenylated 3′ (3-prime) region (adenine-containing nucleotides are added to the mRNA in eukaryotes). These sequences are converted to complementary DNA (cDNA) by the enzyme reverse transcriptase, and then integrated back in the genome at a new location (Figure 1B). These elements, therefore, are not necessarily in the chromosomal vicinity of the original sequence, and are essentially dead on arrival. Processed pseudogenes are also referred to as retropseudogenes.

Processed pseudogenes may also be derived from other RNA genes, such as tRNA (transfer RNA), rRNA (ribosomal RNA), snRNA (small nuclear RNA), and 7SL RNA. Evidence for this phenomenon includes the identification of nonfunctional tRNA genes containing a CCA sequence at the 3′ terminal. CCA is not part of the original DNA sequence, but is enzymatically added to the tRNA molecule following transcription. The gene for 7SL RNA is an integral component of the signal recognition particle complex involved in transmembrane protein transport. The 7SL RNA gene is thought to be the ancestral gene for the primate Alu and rodent B1 retroposons, based on sequence similarities. (Retroposons are a type of transposable genetic element that is found littered throughout the genome.) The Alu element differs from 7SL by having two internal sequence deletions, Figure 3. Evolution of the human globin gene superfamily. Solid boxes represent functional genes, striped boxes represent expressed pseudogenes, and empty boxes represent pseudogenes. duplication of the entire sequence, and numerous nucleotide substitutions. At some point in its evolutionary past a 7SL retropseudogene apparently integrated into a highly fortuitous location, as there are about 1.5 million Alu elements in the human genome, accounting for approximately 10 percent of our DNA. Most Alu elements are retropositionally incompetent pseudogenes, hence incapable of generating additional copies. Other retroposons are thought to be derived from processed duplicated tRNA genes (for example, rodent B2 and ID elements).