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Types of Pseudogenes - Decoding Pseudo Notions

BY: Sandhya Anand | Category: DNA | Submitted: 2011-04-14 03:25:21
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Article Summary: "Psudogenes are DNA sequences which are results of one or more mutations which render them non functional. Apart from these minor changes, the sequences are almost identical to functional gene sequences..."


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Psudogenes are DNA sequences which are results of one or more mutations which render them non functional. Apart from these minor changes, the sequences are almost identical to functional gene sequences. Pseudogenes have been found to constitute the majority of intron sequences.

These pseudogenes have been found to be common in different species of animals rendering them to be classified under the same phylogenetic tree in the course of evolution.

There are mainly two possible mechanisms through which these similarities can occur.
1. The organisms have a common ancestor and the gene sequences underwent common substitutions/mutations. (divergent evolution)
2. The organisms had different ancestors. But, the findings of these similar sequences in different species are the result of similar pattern of substitutions/mutations in gene sequences resulting in similarity.(convergent evolution)


Types of pseudogenes

There are mainly two types of pseudogenes
I. Conventional pseudogenes
II. Processed pseudogenes

I. Conventional pseudogenes

These are genes that have become non functional due to mutations which were accumulated over time. The most common example includes the globin gene clusters in humans which is comprised of five psudogenes. These can also be the result of gene duplication.
Many of these mutations have little or no effect on the gene functionality, however, a few of these may be significant enough even with minor changes such as single nucleotide substitutions. Once it loses its original function, pseuodgenes are found to degrade more with accumulating more number of mutations.

These conventional pseudogenes can further be classified based on their mechanism of origin.
a. Non processed pseudogenes
These are simply non functional and might have inappropriate termination codons. This type of pseudogenes are believed to be the result of tandem gene duplication events and are found commonly in clustered gene families.

b. Expressed non processed pseudogenes
They are the result of gene duplication processes in which one allele integrates the deleterious mutation and subsequently loses its function. In the process of losing the functionality, the gene may be active for a short duration during which it is expressed. For example, sigma globin is expressed without it being a part of the fully functional hemoglobin molecule.

c. Truncated gene segments

Truncated gene segments and/or fragments are another group of pseudogenes and are often found in clustered gene families. These unlike the usual gene duplication/mutation events are thought to be the resultant of unequal cross overs and sister chromatid exchanges. They either lack a stretch of DNA from one end of the parental genome (truncated) or are formed of short isolated sequences found random within the genome.

Characteristics of traditional pseudogenes

a. may not have promoter sequences
b. have mutations which disable the function of gene
c. lost splice sites and hence cannot remove introns during transcription.

However, recent researches have thrown light that these conventional pseudogenes form only a small percentage of the ~ 20000 pseudogenes found in humans. Again, their non functionality is still hard to prove.

II. Processed psudogenes

These are the result of reverse transcription. The genome gets integrated into the reverse transcript genome of an mRNA. This can then integrate itself into its parental or another chromosome. These pseudogenes do not contain any intron sequences since the parent mRNA is devoid of complementary sequences for introns. It also lacks promoter sequences which are found usually in the parent gene. These pseudogenes hence become inactive without the mechanisms for transcription and processing.

As with the traditional pseudogenes, these processed pseudogenes can express themselves.

a. Processed pseuodogenes
These are often made of non functional copies of exon regions from the parental gene sequence. They are found in interspersed gene families and are thought to be the result of natural reverse transcription.

These can be derived either from RNA polymerase II or III. Pol II derived sequences lack promoter sequences and hence is not able to express.
In Pol II derived sequences, the retroposition is thought to result in loss of promoter sequences since they are located upstream to the cap site.

Pol III derived sequences have high copies of sequences such as Alu repeats. This is due to the presence of internal promoters which enables them to undergo several rounds of retroposition.

b. Expressed processed pseudogenes
These pseudogenes can express due to the proximity to the promoter sequences. An example is the PDHA-2 (Pyruvate dehydrogenase) enzyme expression in testes.

The distinction between the functional and pseudogenes was built on certain conventional notions on gene expression.

To be classified as a pseudogene, it was required to satisfy either one or more of the following conditions.

1. The promoter site either absent/ mutated making it non functional.
2. An initiator codon either misplaced/ absent.
3. Presence of an ORF (Open Reading Frame) with several missense mutations
4. ORFs being interrupted by frame shift mutations and premature stop codons making the transcripts incomplete/ meaning less.

The research on pseudogenes have made the scientific community to redefine these parameters since some pseudogenes are found to have regulatory roles in gene expression.

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