[go] ISA/ISO

[Valerie Wood]

We can't exclude things from being true orthologs just because we can't 
detect sequence similalrity using current methods. However we need to be 
critical when assessing the information.

I also have examples where things are functional orthologs (functionally 
equivalent) and are not considered to be true orthologs (i.e separated 
by a speciation event) , like rum1, which is the functional ortholog of 
S. cerevisiae sic1, but is not proposed to be a true ortholog.

Val

Pankaj Jaiswal wrote:

> This seems like a case for 'functional ortholog' based on the 
> conserved assembly and interaction among subunits of a protein complex 
> from two different species. We see these cases quite often.
>
> Here is an interesting paper on this theme
> Systematic identification of functional orthologs based on protein 
> network comparison. Genome Res. 2006 Mar;16(3):428-35.
> PMID: 16510899
> http://www.ncbi.nlm.nih.gov/pubmed/16510899?dopt=Abstract
>
> Pankaj
>
>
> Gwinn Giglio, Michelle wrote:
>
>>
>>
>>
>> Hi Val,
>>
>> The definition of ortholog is that the two sequences arose from a common
>> ancestor and were separated by a speciation event.  The situation you
>> describe sounds to me like there is good evidence that the two proteins
>> carry out the same functions, however they could either be orthologs 
>> that
>> have diverged so much that no recognizable sequence similarity 
>> remains or
>> they have arisen due to convergent evolution and are NOT true orthologs.
>>
>> Michelle
>>
>>
>>
>>
>> On 2/21/08 8:54 AM, "Valerie Wood" <val at sanger.ac.uk> 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
>>>
>>>
>>
>>
>



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