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Pseudogenes - Function and Origin

BY: Sandhya Anand | Category: DNA | Submitted: 2011-04-16 19:08:48
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Article Summary: "The article summarizes the origin, location, features and functions of pseudogenes. The pseudogenes were identified during the late 1970s when the function of genes was mapped onto the chromosome locations. They were named pseudogenes since they were thought to have no functionality.."


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The pseudogenes were identified during the late 1970s when the function of genes was mapped onto the chromosome locations. They were named pseudogenes since they were thought to have no functionality.

Origin
Pseudogenes are thought to be derived from functional parent genes. The original parental genes undergo changes in gene sequences due to mutations or any such abnormalities resulting in non functional copies. These defects include

a. loss of start codon
b. additional stop codons
c. lack of regulatory sequences
d. presence of abnormal regulatory sequences
e. Duplication event result in formation of pseudogenes when the cell's genome replicates and integrates an extra copy of the gene into another location of the chromosome.

A vast number of pseudogenes are thought to be formed as a result of retrotransposition of transcripts derived from functional genes. The retrotransposition was responsible for rendering the genes non functional.

However, with the recent discoveries of pseudogenes having novel functions, this definition needs to be modified.

Features
Processed pseudogenes
They can arise either by errors in transcription or retrotranscription followed by integration. They are characterized by
a. Absence of promoter sequence at 5'end and introns
b. Presence of 3'poly A tract.
c. Flanking direct repeats
d. Integrates randomly into the parental gene
Non processed pseudogenes are characterized by
a. their vicinity to the functional paralogous gene sequence
b. presence of introns

Location
Pseudogenes are found to be located on chromosomes in way that they do not interfere with the normal functioning and fitness of the organism. Non processed pseudogenes are found in clustered gene families.

Mitochondrial pseudogenes are found in many animal species. In the animal lineage, the mitochondrial genome has lost considerable sequences in the process of transfer of genes to the nucleus. These transfers can be either through direct DNA transfer or mediated through RNA. Such transfers when unsuccessful are thought to result in formation of pseudogenes. Most of the available experimental data suggest for direct DNA transfer mechanism.

The mitrochondrial pseudogenes are almost absent in fishes while abundantly present in mammals and most avian species. For example, the experimental models Drosophilia (3) and Caenorhabditis (2) have very few pseudogenes.


Function
Psudogenes were originally thought to be without any function. Recently, regulatory roles have been confirmed for human pseudogenes. Active transcription of these intergenic regions was confirmed by the research of Thomas Gingeras and Michael Snyder.

The chances of pseudogenes resurrecting back to functional genes are also fair. One such example is a cow gene for a ribonuclease enzyme which has been reactivated during the evolutionary lines.

The human pseudogene NA88-A was thought to be a defective copy of the HYX42B gene which codes for homeoprotein. The pseudogene has been found to produce a tumor rejection antigen. The peptide is transcribed from an alternative short ORF (Open reading frame). There is a premature stop codon in the pseudogene which was found to be essential for production of this antigenic peptide.

Significance

The pseudogenes can interfere with the PCR and in situ hybridization experiments due to their similarity with the parental genes. Exact mapping of these pseudogenes onto chromosomes is extremely difficult and requires more sophisticated approaches than hybridization. Multiple pseudogenes of the same sequence are found in human genes which could have an effect on the diagnosis of disease and genome evolution.

• They form a molecular record of the evolutionary history and dynamics of the parental genome.
• The absolute rate of mutation is lower in nucleus than the one occurring in mitochondria. A study on mitochondrial pseudogenes is therefore advantageous in deciphering phylogeny.
• Processed pseudogenes undergo retrotranscription. A comparison of the original and retrotranscribed copies of the pseudogene can reveal the necessary environmental conditions. Often duplication and diversification rates are higher for genes which enable the organisms to respond to the environmental stimuli. The olfactory receptor repertoire is one such large gene family. Pseudogenes are often the byproducts of such processes. Any difference in the pseudogene sequences between related animals can therefore show the diverse habitats of the concerned organisms.
• They are also useful to find the rate of nucleotide substitutions, DNA loss etc.
• The evolutionary processes and their rates can be studied better with the pseudogenes. This has led to the formation of the field of pseudogenomics.

Evolutionary fate of the pseudogenes

Generally pseudogenes never undergo transcription and undergo genetic drift. But in a few cases, they remain conserved and do not succumb to the pressures of natural selection. Very few of these pseudogenes are transcribed and some are found to have novel functions.

A retropseudogene can undergo
a. Compositional assimilation and
b. reduction in pseudogene size

Compositional assimilation is a rapid accumulation of point mutations which cause the functional gene to be different from the pseudogene. The processed pseudogene will be more similar to the surrounding non functional gene sequences.
Pseudogenes also get reduced in size with evolution due to the excessive deletions over insertions. A processed pseudogene is estimated to lose approximately fifty percent of the original DNA sequence in 400 million years. Other factors such as natural selection are also found to favor such shrinkage.

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