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annotating to pseudogenes

Karen Christie kchris at genome.Stanford.EDU
Wed Mar 15 09:46:15 PST 2006


Hi,

My comment here is more about the SO definition of pseudogene, than about
whether or not to use GO terms to annotate features given that label.

I was thinking about the SO definition of pseudogene this morning and was
wondering if part of the problem is that the definition may have been
written from a protein-centric view of genes and what the possible
functions of genes are. If I understand correctly, and Rama and some of
the other people who are more up on pseudogenes may correct me, most
pseudogenes have been designated as such by virtue of being 1) similar to
a known protein-coding gene and 2) being thought to NOT express that
particular protein that might have been expected based on its similarity
to a known protein coding gene. In other words, most people when
designating something as a pseudogene were only thinking about it's
protein coding ability. It seems that all of the cases that people have
mentioned in this thread where a pseudogene is expressed result in the
production of an RNA from a pseudogene that resesmbles a protein, thus the
pseudogene is not producing the gene product that it might have been
expected to have based on its sequence similarity to a protein coding
gene. It seems to me that even when it has been discovered that a
"pseudogene" produces an RNA transcript that may have activity in
regulating the gene it is related to, that the community still calls these
"pseudogenes" because they do not produce the protein product expected
based on sequence similarity to the known functional gene.

It seems possible that there may be pseudogenes of ncRNA genes as well of
protein coding genes, but perhaps we can revise the definition of
pseudogene to be a little more accurate. While GO and SO do need to be
precise and rigorous, often more so than the literature, we also do need
to reflect the community usage of terms.

Here's my thoughts on a possible revision of the SO def of pseudogene; the
current SO def is below.

Possible revision:

def: "A sequence that closely resembles a known functional gene, at
another locus within a genome, that is thought to be non-functional, with
respect to producing the expected gene product based on sequence
similarity with the known functional gene, as a consequence of (usually
several) mutations that prevent either its transcription or translation
(or both). In general, pseudogenes result from either reverse
transcription of a transcript of their \"normal\" paralog (SO:0000043) (in
which case the pseudogene typically lacks introns and includes a poly(A)
tail) or from recombination (SO:0000044) (in which case the pseudogene is
typically a tandem duplication of its \"normal\" paralog)."
[http://www.ucl.ac.uk/ ~ ucbhjow/b241/glossary.html] subset: SOFA


Current SO def:

def: "A sequence that closely resembles a known functional gene, at
another locus within a genome, that is non-functional as a consequence of
(usually several) mutations that prevent either its transcription or
translation (or both). In general, pseudogenes result from either reverse
transcription of a transcript of their \"normal\" paralog (SO:0000043) (in
which case the pseudogene typically lacks introns and includes a
poly(A) tail) or from recombination (SO:0000044) (in which case the
pseudogene is typically a tandem duplication of its
\"normal\" paralog)." [http://www.ucl.ac.uk/ ~ ucbhjow/b241/glossary.html]
subset: SOFA





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