Pseudogenes, denoted by the Greek letter psi, are genes that were once functional, but that, due to mutations, have lost that function. Pseudogenes may be processed or non-processed. The former contain only exons, while the latter are copies of entire genes. Pseudogenes can arise from gene or genome duplications, where one copy has lost its function, or from the mutation of a non-essential, single-copy gene. Occasionally, processed pseudogenes can retain their function.
Processed pseudogenes can consist of a full or a partial copy of the functional gene's mRNA, or they may contain sequences other than those found in the functional gene. They have no introns, a poly-A tail at the 3' end, and flanking direct repeats. They arise when an mRNA is reverse-transcribed into cDNA and inserted into the genome by an endogenous or viral reverse transcriptase. Many processed pseudogenes are derived from genes transcribed by RNA pol II and contain internal promoter sequences such as Alu elements. RNA pol III may be responsible for transcribing those processed pseudogenes which are not exact copies of their functional counterparts. Processed pseudogenes are usually not expressed, as their sequence does not include a promoter. They can only be transcribed if the cDNA integrates near a promoter, in which case the gene could retain its function if the coding sequence does not contain errors that would destroy the functionality of the resulting protein. Functional processed pseudogenes include pyruvate dehydrogenase, phosphoglycerate kinase, glycerol kinase, and glycerol dehydrgenase, and are of relatively recent origin.
Non-processed pseudogenes can be unitary or duplicated. Unitary pseudogenes are comparatively rare and arise from the mutation of single-copy genes. Once a gene has become a unitary pseudogene, no functional copy remains. For a unitary pseudogene to persist, the organism must not suffer any disadvantage due to the loss of function. An example of such a unitary pseudogene is GLO in primates (including humans) and guinea pigs, which when active synthesises ascorbic acid. Primates and guinea pigs must compensate for the inactivity of GLO by comsuming ascorbic acid (vitamin C) in their diet. Duplicated pseudogenes are the most common and are believed to have arisen as a result of gene and genome duplications. One copy of the gene remains active, while the other gathers mutations that render it non-functional. The continued presence of a functional gene means that the pseudogene is not selected against and is free to degenerate.
Non-processed pseudogenes are copies of whole genes, including introns. They can include flanking sequences and multiple termination codons. They are often found in gene clusters, where they arise by gene duplication then diverge by means of a frame-shifting or chain-terminating mutation.
Processed and non-processed pseudogenes differ in their structure and origins but, with a few rare exceptions, share the characteristic of being non-functional versions of normal genes. Non-processed pseudogenes are the natural consequence of gene duplication and mutation.