Pseudogenes, also known as noncoding DNA, are extra DNA in a genome that do not get transcribed into RNA to synthesize proteins. Some of this noncoding DNA has known functions, but much of it has no known function and is called "Junk DNA". This is an example of a vestige since replicating these genes uses energy, making it a waste in many cases. Pseudogenes make up 99% of the human genome (1% working DNA). A pseudogene can be produced when a coding gene accumulates mutations that prevent it from being transcribed, making it non-functional. But since it is not transcribed, it may disappear without affecting fitness, unless it has provided some new beneficial function as non-coding DNA. Non-functional pseudogenes may be passed on to later species, thereby labeling the later species as descended from the earlier species.

Types and origin of pseudogenes

There are three main types of pseudogenes, all with distinct mechanisms of origin and characteristic features. The classifications of pseudogenes are as follows:

1. Processed (or retrotransposed) pseudogenes. In higher eukaryotes, particularly mammals, retrotransposition is a fairly common event that has had a huge impact on the composition of the genome. For example, somewhere between 30% - 44% of the human genome consists of repetitive elements such as SINEs and LINEs (see retrotransposons). In the process of retrotransposition, a portion of the mRNA transcript of a gene is spontaneously reverse transcribed back into DNA and inserted into chromosomal DNA. Although retrotransposons usually create copies of themselves, it has been shown in an in vitro system that they can create retrotransposed copies of random genes, too.[8] Once these pseudogenes are inserted back into the genome, they usually contain a poly-A tail, and usually have had their introns spliced out; these are both hallmark features of cDNAs. However, because they are derived from a mature mRNA product, processed pseudogenes also lack the upstream promoters of normal genes; thus, they are considered "dead on arrival", becoming non-functional pseudogenes immediately upon the retrotransposition event. However, occasionally these insertions contribute exons to existing genes and usually via alternatively spliced transcripts. A further characteristic of processed pseudogenes is common truncation of the 5' end relative to the parent sequence, which is a result of the relatively non-processive retrotransposition mechanism that creates processed pseudogenes.

2. Non-processed (or duplicated) pseudogenes. Gene duplication is another common and important process in the evolution of genomes. A copy of a functional gene may arise as a result of a gene duplication event and subsequently acquire mutations that cause it to become nonfunctional. Duplicated pseudogenes usually have all the same characteristics of genes, including an intact exon-intron structure and promoter sequences. The loss of a duplicated gene's functionality usually has little effect on an organism's fitness, since an intact functional copy still exists. According to some evolutionary models, shared duplicated pseudogenes indicate the evolutionary relatedness of humans and the other primates. If Pseudogenization it is due to gene duplication, it usually occurs in the first few million years after the gene duplication provided the gene is not been subjected to any selection pressure. The functional redundancy will be generated by gene duplication and mostly it is of course not advantageous to carry two identical genes, and mutations that disrupts either structure or function of any one of the two genes are not deleterious and will not be removed through selection process. As a result, that gene that has been mutated gradually becomes a pseudogene and will be either unexpressed or functionless. This kind of evolutionary fate is shown by population genetic modeling] and also by genome analysis. These pseudogenes according to evolutionary context will either be deleted or become so distinct from the parental genes so that they will be no more identifiable. Relatively young pseudogenes can be recognizable due to their sequence similarity.

3. Disabled genes, or unitary pseudogenes. Various mutations can stop a gene from being successfully transcribed or translated, and a gene may become nonfunctional or deactivated if such a mutation becomes fixed in the population. This is the same mechanism by which non-processed genes become deactivated, but the difference in this case is that the gene was not duplicated before becoming disabled. Normally, such gene deactivation would be unlikely to become fixed in a population, but various population effects, such as genetic drift, a population bottleneck, or in some cases, natural selection, can lead to fixation. The classic example of a unitary pseudogene is the gene that presumably coded the enzyme L-gulono-γ-lactone oxidase (GULO) in primates. In all mammals studied besides primates (except guinea pigs), GULO aids in the biosynthesis of Ascorbic acid (vitamin C), but it exists as a disabled gene (GULOP) in humans and other primates. Another interesting and more recent example of a disabled gene, which links the deactivation of the caspase 12 gene (through a nonsense mutation) to positive selection in humans.

Pseudogenes can complicate molecular genetic studies. For example, a researcher who wants to amplify a gene by PCR may simultaneously amplify a pseudogene that shares similar sequences. This is known as PCR bias or amplification bias. Similarly, pseudogenes are sometimes annotated as genes in genome sequences.

Processed pseudogenes often pose a problem for gene prediction programs, often being misidentified as real genes or exons. It has been proposed that identification of processed pseudogenes can help improve the accuracy of gene prediction methods.

It has also been shown that the parent sequences that give rise to processed pseudogenes lose their coding potential faster than those giving rise to non-processed pseudogenes.


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