[go] ISA/ISO

[Valerie Wood]

Hi Michelle,

It could, but the species distribution of the proteins, the fact that 
they are conserved in  most yeast species but the level of  similarity 
is very low, and their phenotypes and interaction implies they are 
orthologs. The community refer to them as orthologs, because the 
assumption is that they arose from a speciation event. It is the most 
parsimonious solution for the experimental data. A similar sequence can 
also arise from a convergence so sequence similarity alone is not enough 
to exclude a convergence event.

This particular complex is uniformly conserved from yeast to humans, 
except for the subunits nse5 and nse6 (the same name in both organisms) 
which are identified only in fungi  at present ( single copy in all 
species where identified). I think there is enough information here to 
make an orthology call and infer that these analogous subunits of the 
same conserved complex are orthologous. The subunits are probably also 
present in metazoans, but have not yet been detected because they are so 
divergent.
Identifying the orthologs of nse1 was also tricky but we have alignments 
for these
http://pfam.sanger.ac.uk/family?acc=PF07574
I could probably build an alignment for nse6 if I included the 2 as yet 
unpublished schizos.

The yeast community have been increasingly linking up the remaining 
orthologs in the 'orphan set'  by experiment (usually subsequently  
supported by alignment, for many years),below are some recent  examples, 
most of these are below the levels immediately detectable by sequence 
similarity (these methods have now been exhausted) so we are relying on 
complex membership/structure for the initial clues.

In most cases a valid alignment can (and is ) built, but the primary 
source of the orthology inference is the experimental data.

Val

SPCC338.08    YGL075C CtIP-related protein (pers. comm. P. Russell)
SPAC6B12.02c    YLR320W DNA repair protein Mus7/Mms22  (PMID: 17660542)
SPBC1718.07c YLR136C|YDR151C human Tristetraprolin homolog Zfs1
SPCC777.08c  YJL058C|YBR270C TORC2 subunit Bit61 (PMID: 18076573)
SPCC162.12 YPL180W TORC1 subunit Tco89 (PMID: 18076573)
SPCC1442.02    YGL060W conserved fungal protein (pers. comm. E. Hartsuiker)
SPBC16C6.03c YPL193W conserved fungal protein (pers. comm. E. Hartsuiker )
SPAC17G8.05 YHR041C Mediator complex subunit Med20 (from PMID:15175151)
SPBC6B1.04 YDR439W monopolin-like complex subunit Mde4 (from PMID:17627824)
SPBC25D12.02c YKR010C nucleolar protein Dnt1 (from PMID:17538026)
SPAC343.18 YDL013W ubiquitin-protein ligase E3 Rfp2 (pers.comm. M.Nick. Boddy)
SPAC19A8.10 YDL013W ubiquitin-protein ligase E3 Rfp1 (pers.comm. M.Nick. Boddy)
SPBC409.12C YDR082W nuclear telomere cap complex subunit Stn1 (pers.comm. Paul Russell)
SPCC1393.14  YLR010C nuclear telomere cap complex subunit Ten1 (pers.comm. Paul Russell, is also a new gene)
SPAC1250.07    YOR110W TFIIIC subunit Sfc7 PMID:17409385








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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