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[SO-devel] Re: annotating to pseudogenes

Karen Christie kchris at genome.Stanford.EDU
Mon Mar 20 09:33:40 PST 2006


Hi

I have a question along the lines of Val's comment. I was wondering what
the scientific community would expect to see with respect to how a
"pseudogene" that expresses a transcript would be annotated in SO. Suzi
has said that if a pseudogene is discovered to express a transcript, than
the 'pseudogene' annotation should be removed and replaced with something
else, i.e. 'ncRNA'. However, is that consistent with what the people
studying these do, i.e. if they discover that a 'pseudogene' is expressed,
do they stop calling it a 'pseudogene'? I'm not sure that they do.

In the exposure to this issue that I've had, it seems that people DO
continue to call it a pseudogene, but add the adjective 'expressed' so
that they now refer to it as an 'expressed pseudogene'. If this is common
practice, to refer to 'pseudogenes', i.e. genes that don't express the
product they might have been expected to based on sequence similarity to a
functional gene, that actually do express a product, often an ncRNA, as
'expressed pseudogenes', then perhaps SO should reflect that usage, rather
than impose a perhaps artificially strict definition that pseudogenes
never express any product. Perhaps we could have a SO term for 'expressed
pseudogene' to capture this particular class of features, perhaps with
dual parentage both under 'pseudogene' and under 'ncRNA'.

Like I said at the beginning, this is a question about how would
researchers expect an 'expressed pseudogene' to be annotated, and I'm far
from an expert on pseudogenes. I'm also more familiar with GO practice
that SO, but it seems that if researchers still refer to a feature as a
pseudogene, even after it has been discovered to produce a transcript that
may function as an ncRNA, then SO should attempt to reflect the usage of
the research community.

-Karen



On Mon, 20 Mar 2006 val at sanger.ac.uk wrote:

> 
> 
> So, if a gene with a degraded protein coding CDS was found to have functionality 
> as a ncRNA, can you annotate:
> 
> i) a ncRNA feature (with appropriate GO terms)
> ii) the degraded CDS region as a pseudogene, or pseudogenic exon or whatever
> 
> It sounds as if not, but for complete annotation of features you would probably 
> still want to capture the degraded protein coding region. Certainly this would 
> be useful information to anybody who didn't know the full history of the 
> feature. Is there any reason that both cannot be captured as different partially 
> overlapping feature types?
> 
> Val
> 
> 
> 
> 
> Quoting Suzanna Lewis <suzi at fruitfly.org>:
> 
> > 
> > On Mar 19, 2006, at 9:52 AM, Karen Eilbeck wrote:
> > 
> > > Before we all agree on the proposed definition for pseudogenes, we  
> > > need to address some issues.
> > > Firstly if we use this definition, then a region that is a pseudogene  
> > > that turns out to also be a functional non-coding RNA, will also be a  
> > > ncRNA.
> > > I'm not sure if this will affect supporting software.
> > 
> > Non, non, mon cheri.
> > 
> > If it turns out to be a functional non-coding RNA then it is *not* a  
> > pseudogene (even with this modified definition). The annotation calling  
> > it a "pseudogene" would necessarily have to be updated (removed) as  
> > soon as proof of functionality is found.
> > 
> > -S
> > 
> > >
> > > Secondly the definition is supposed the explicitly describe the  
> > > feature, and the phrase "that is thought to be" adds vagueness rather  
> > > than clarity.
> > >
> > > I'm sure there will ample discussion of this term in St Croix.
> > >
> > > --Karen
> > >
> > >
> > >
> > > On Mar 19, 2006, at 5:27 AM, Richard Durbin wrote:
> > >
> > >> Thank you for this thoughtful analysis and proposal. I support the  
> > >> revised definition as well.
> > >> Richard
> > >>
> > >> Michael Ashburner (Genetics) wrote:
> > >>
> > >>> I could live with that changed definition.
> > >>> Michael
> > >>>
> > >>>
> > >>>> Envelope-to: ma11 at gen.cam.ac.uk
> > >>>> Delivery-date: Wed, 15 Mar 2006 18:44:22 +0000
> > >>>> X-Cam-SpamDetails: scanned, SpamAssassin (score=0)
> > >>>> X-Cam-AntiVirus: No virus found
> > >>>> X-Cam-ScannerInfo: http://www.cam.ac.uk/cs/email/scanner/
> > >>>> From: Karen Christie <kchris at genome.stanford.edu>
> > >>>> To: Hubert Renauld <hjr at sanger.ac.uk>
> > >>>> Cc: ruth at galton.ucl.ac.uk, Karen Eilbeck <eilbeck at fruitfly.org>,
> > >>> ...
> > >>>
> > >>>> List-Archive:  
> > >>>> <http://sourceforge.net/mailarchive/forum.php?forum=song-devel>
> > >>>> Date: Wed, 15 Mar 2006 09:46:15 -0800 (PST)
> > >>>>
> > >>>> 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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> > 
> > 
> > 
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