I think you are confusing a few different things here, and there is some information that is lacking. The information that is lacking in this discussion is whether the hits for the domains occur at the same spot on the protein, remember a protein can be composed of many domains, if your hmmsearch is returning hits to different portions of your protein, the interpretation of those results are different than when you have two good hits that overlap.
Now, assuming we are talking about a situation where you have two good (as determined by the e-value) hits to the same region of your query protein sequence, if the two domains with hits are closely related to one another (part of the same PFam family, etc) this is the exact same situation as if you were running a BLAST search. You expect to get multiple matches with good e-values in different species, both orthologs and paralogs. With domains there are fewer of them, so you don't always have these results, but it is still expected in many cases.
Also, it is very important to keep in mind, that domains and proteins are two different "units" and we can talk about the evolution of domains and of whole proteins somewhat independently of one another. While related domains are probably often generated by gene duplication and divergence of genes, there are other a host of other processes at play driving that differentiation (exon shuffling, domain re-arrangement, recombination, translocation, etc).
In summary, and the short answer, no you cannot say that what you have represents an intermediate sequence between the two domains. All you know is that you have a domain in your protein sequence that shows strong evidence of being homologous to both domains in question, but that isn't unusual or unexpected in most cases.
7.0 years ago by
DG ♦ 7.2k