[go] ISA/ISO

[Gavin Sherlock]

As pointed out by many people, orthologs are defined as proteins in  
two species that arose from a common ancestor, and diverged from a  
speciation event.  It can be 1:1, 1:n, or n:n.  We usually infer  
orthology based on sequence similarity (with additional constraints;  
choose your favorite algorithm); however, this is not a requirement.   
If we can infer it from other data, such as synteny, comparative  
genomics, transitive homology across multiple organisms - this is  
also fine.  It seems to me that inferring orthology between proteins  
based on their existence in conserved complexes is merely an  
additional method (for which the bar may be set higher as needs be).   
The definition of orthology does not preclude this type of data from  
being used to make the inference, though people's faith in the  
inference may differ than one based on sequence similarity.

Cheers,
Gavin

On Feb 21, 2008, at 11:56 AM, Benjamin Hitz wrote:

>
> Val -
> This is a bad example.
>
> Orthology implies an evolutionary relationship.  If there is no  
> detectable sequence similarity and no detectable structural  
> similarity, I don't see there is any evidence for an evolutionary  
> relationship.
>
> I think for both Nse6 (Pombe) and presumed orthologes in other  
> species - there is no known structure, hence you cannot conclude  
> whether or not they have a similar (analgous?) function due to  
> convergent or divergent evolution.
>
> Ben
>
>
> On Feb 21, 2008, at 5:54 AM, Valerie Wood wrote:
>
>> In support of the final sibling arrangement of ISA/ISO, I came  
>> across an example today where gene products are known to be  
>> orthologous but have no sequence conservation which I thought I  
>> would share.
>>
>> Identification of the Proteins, Including MAGEG1, That Make Up the
>> Human SMC5-6 Protein Complex
>> Elaine M. Taylor, Alice C. Copsey, Jessica J. R. Hudson, Susanne  
>> Vidot, and Alan R. Lehmann
>> quote
>> "Nse6 contains ARM/HEAT repeats, but there is no sequence  
>> conservation between these presumed orthologs from S. cerevisiae/  
>> and /S. pombe/. In /S. pombe/ they also appear to bridge the head  
>> domains of Smc5 and Smc6"
>>
>> where it is not even possible to detect the similarity between the  
>> 2 nse6 subunits in yeast and pombe but they are presumed orthologs  
>> from other biological properties and position in the complex,  
>> binding partners etc.
>> These are NOT reciprocal best hits, and although they can be  
>> aligned, (you can align anything) it does not mean, that if I  
>> inferred any  experimental data from the S. cerevisiae ortholog it  
>> would come from a sequence alignment.
>>
>> I should also add that this is very common which also has large  
>> implications for the orthology prediction exercise.
>>
>>
>> Val
>>
>>
>>
>> -- 
>> The Wellcome Trust Sanger Institute is operated by Genome Research  
>> Limited, a charity registered in England with number 1021457 and a  
>> company registered in England with number 2742969, whose  
>> registered office is 215 Euston Road, London, NW1 2BE.
>
> --
> Ben Hitz
> Senior Scientific Programmer ** Saccharomyces Genome Database ** GO  
> Consortium
> Stanford University ** hitz at genome.stanford.edu
>
>