Hello,

If I have a set of orthologous proteins, it is assumed that these will have a shared function due to the maintenance of evolutionary pressure following speciation (as I understand).  

If I have a set of proteins that fall within a single PFAM, is the assumption of shared functionality as strong as it would be for the ortholog group?  I am guessing not, as the second paragraph of the reference's introduction explicitly says they do not always share function.  But then, no assumption is complete, so I imagine there will also be orthologs that do not share function.  

I assume there is a degree of uncertainty regarding how high quality the group of orthologs is (e.g. if it is found by RSD or RBH or tree based methods).  But with that in mind, would you say the assumption of shared functionality is stronger for the PFAM group or for the orthologous group?

Thanks!


Reference:
Nucleic Acids Research, Volume 47, Issue D1, 08 January 2019, Pages D427–D432, https://doi.org/10.1093/nar/gky995


Edit - for anyone interested there's some interesting discussion here - https://www.biostars.org/p/128/#128 
I would say stronger for the orthologous groups than in the PFAM groups. The pfam works only on conserved domains, while orthogroups (usually) take the whole sequence into account.

Moreover, it is not because you share a certain domain that you then also share a common function. Most eukaryotic proteins have a multi domain structure and thus the true biological function is a combination of those domains rather than 1 specific domain (though that also exists in eukaryotes).  Some domain are very common (kinase domain, DNA binding, ... ) and others are quite specific. 

If solely the absence or presence of a domain would determine function (and/or orthology) the problem of orthology defining would have been solved already (which it is not unfortunately)