What are pseudogenes?
Pseudogenes are genomic DNA sequences similar to normal genes but
non-functional; they are regarded as defunct relatives of functional genes.
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What causes pseudogenes to arise?
There are two accepted processes during which pseudogenes may arise:
- duplication - modifications (mutations, insertions, deletions,
frame shifts) to the DNA sequence of a gene can occur during duplication.
These disablements can result in loss of gene function at the transcription
or translation
level (or both) since the sequence no longer results in the production of
a protein. Copies of genes that are disabled in such a manner are termed
non-processed or duplicated
pseudogenes.
- retrotransposition - reverse transcription of an mRNA transcript
with
subsequent re-integration of the cDNA into the genome. Such copies of genes
are termed
processed pseudogenes. These pseudogenes can also accumulate
random
disablements over the course of evolution.
Click here for a graphical illustration of this definition.
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Why are pseudogenes interesting?
In any study of molecular evolution, it is necessary to compare and contrast
genes from a variety of organisms to gauge how the organisms have adapted to
ensure their survival. Pseudogenes are vitally important since they
provide a record of how the genomic DNA has been changed without such
evolutionary pressure and can be used as a model for determining the
underlying rates of nucleotide substitution, insertion and deletion in the
greater genome.
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How can a pseudogene be identified?
Once gene sequences have been identified in the genome, it is possible to
use sequence alignment programs (such as FASTA or BLAST) to detect matching
regions in the nucleotide sequence. These matching regions are potential
gene homologs and are termed pseudogenes if there is some evidence that
either of the causes (see above) are satisfied.
In these analyses, genes from annotated genomes and protein databases have
first been clustered into paralog families and then used to survey whole
genomes
for copies or homologs. For each potential pseudogene (or fragment) match,
a number of steps have been taken to assess its validity as a pseudogene.
These steps include checking for overcounting and repeat elements, overlap
on the genomic DNA with other homologs and cross-referencing with exon
assignments from genome annotations. The resulting pseudogenes or pseudogenic
fragments have then been assigned to the paralog family of the most homologous
gene (or assigned to a singleton gene if the probe gene has no obvious
paralog).
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Relating pseudogenes to known protein
structures
In a number of cases, more distant evolutionary and functional relationships
between proteins can only be elucidated through the analysis of the folds that
their structures adopt. While it must not be forgotten that the assignment of
function to a gene is often implied from that of a gene with a homologous
sequence, the added information that protein structures can provide is very
desirable in genome annotation.
In the case of pseudogenes, structural information can give extra evolutionary
clues and facilitate analysis of the scope of folds in the pseudogene
population ("pseudo"-folds) in contrast to those observed for the genes
themselves. Where possible, i.e. where a gene can be matched to a SCOP domain,
assignment of fold to a pseudogene or pseudogenic fragment is based upon the
assignment of the most homologous gene.
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Our analyses
Our initial goal was to survey some eukaryotic genomes for pseudogene
sequences
and fragments of pseudogene sequences. In addition to this, we have also
quantified "pseudo-fold" usage, amino-acid composition, and single-nucleotide
polymorphisms (SNPs) to help elucidate the relationships between pseudogene
families across these organisms.
Click here for results of our
pseudogenes analyses.
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