[go] ISA/ISO

[Pankaj Jaiswal]

This is fine, as you said, a lot depends on the parameters and cutoff. 
Many default parameters are very strict. For a protein structure 
prediction experiment, the protein is likely to fold in a conserved way 
if there is about 28-31% identity for an overall length. ANd might even 
produce the same interactions if part of a complex. Which can be used to 
find conserved structure and function even though there is not a great 
amount of sequence homology. Where as in general this may not be a good 
enough score to call it a true ortholog (it is still a homolog 
STRUCTURAL AND FUNCTIONAL). So we need to define clearly whether we are 
talking about the homology and orthology.


Pankaj

Valerie Wood wrote:
> 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
>>>>
>>>>
>>>
>>>
>>
> 
> 
> 

-- 
Pankaj Jaiswal
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Dept. of Plant Breeding and Genetics
Cornell University
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