Pseudogene

Pseudogenes are segments of DNA that are related to real genes. Pseudogenes have lost at least some functionality, relative to the complete gene, in cellular gene expression or protein-coding ability. Pseudogenes often result from the accumulation of multiple mutations within a gene whose product is not required for the survival of the organism, but can also be caused by genomic copy number variation (CNV) where segments of 1+ kb are duplicated or deleted. Although not fully functional, pseudogenes may be functional, similar to other kinds of noncoding DNA, which can perform regulatory functions. The 'pseudo' in 'pseudogene' implies a variation in sequence relative to the parent coding gene, but does not necessarily indicate pseudo-function. Despite being non-coding, many pseudogenes have important roles in normal physiology and abnormal pathology. Pseudogenes are segments of DNA that are related to real genes. Pseudogenes have lost at least some functionality, relative to the complete gene, in cellular gene expression or protein-coding ability. Pseudogenes often result from the accumulation of multiple mutations within a gene whose product is not required for the survival of the organism, but can also be caused by genomic copy number variation (CNV) where segments of 1+ kb are duplicated or deleted. Although not fully functional, pseudogenes may be functional, similar to other kinds of noncoding DNA, which can perform regulatory functions. The 'pseudo' in 'pseudogene' implies a variation in sequence relative to the parent coding gene, but does not necessarily indicate pseudo-function. Despite being non-coding, many pseudogenes have important roles in normal physiology and abnormal pathology. Although some pseudogenes do not have introns or promoters (such pseudogenes are copied from messenger RNA and incorporated into the chromosome, and are called 'processed pseudogenes'), others have some gene-like features such as promoters, CpG islands, and splice sites. They are different from normal genes due to either a lack of protein-coding ability resulting from a variety of disabling mutations (e.g. premature stop codons or frameshifts), a lack of transcription, or their inability to encode RNA (such as with ribosomal RNA pseudogenes). The term 'pseudogene' was coined in 1977 by Jacq et al. Because pseudogenes were initially thought of as the last stop for genomic material that could be removed from the genome, they were often labeled as junk DNA. Nonetheless, pseudogenes contain biological and evolutionary histories within their sequences. This is due to a pseudogene's shared ancestry with a functional gene: in the same way that Darwin thought of two species as possibly having a shared common ancestry followed by millions of years of evolutionary divergence, a pseudogene and its associated functional gene also share a common ancestor and have diverged as separate genetic entities over millions of years. Pseudogenes are usually characterized by a combination of homology to a known gene and loss of some functionality. That is, although every pseudogene has a DNA sequence that is similar to some functional gene, they are usually unable to produce functional final protein products. Pseudogenes are sometimes difficult to identify and characterize in genomes, because the two requirements of homology and loss of functionality are usually implied through sequence alignments rather than biologically proven. Pseudogenes for RNA genes are usually more difficult to discover as they do not need to be translated and thus do not have 'reading frames'. Pseudogenes can complicate molecular genetic studies. For example, amplification of 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. Recently 140 human pseudogenes have been shown to be translated. However, the function, if any, of the protein products is unknown.