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annotating to pseudogenes

Suzanna Lewis suzi at fruitfly.org
Wed Mar 15 13:17:23 PST 2006


I think we are getting close enough that, both in terms of time before 
we are together and thoroughness of discussion on the varied issues, to 
move closure to our upcoming meeting.

Karen points are quite true. The is protein centrism in the community. 
The GOC, on the other hand, has clearly stated from the outset that we 
are annotating all gene products, both proteins and functional RNAs. We 
should continue to adhere to this policy. Similarity to a protein 
coding genes, but non-protein coding does not, by any means, imply that 
function has been lost.

All of the formal definitions I have seen (SO and pseudogene.org 
included) take the traditional approach. A pseudogene is 
non-functional. Not a non-functional protein coding gene, but strictly 
non-functional. Given this....

This returns us to the operational question that both Sue, Rama, Barry 
(indirectly), and others have raised. If you don't yet know, then how 
can anyone state categorically that anything is 'non-functional'. 
Simply because we are as yet unaware of the function, we dare not infer 
from this lack of evidence that this thing lacks function.

And yet we do know that things break

And further we know that things are resurrected and used from the 
junkyard. The state of non-functionality may be transient over 
evolutionary time.

Is everything a 'potogene'?


On Mar 15, 2006, at 12:55 PM, Mike Cherry wrote:

> There is a site devoted to pseudogenes, their identification and 
> analysis, Mark Gerstein's lab at Yale.
>
> http://pseudogene.org/
>
> On this page you'll find some definitions:
>
> http://pseudogene.org/background.php
>
> -Mike
>
> On Mar 15, 2006, at 9:46 AM, Karen Christie wrote:
>
>> 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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