Abstract
The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.
Highlights
The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs
Does the similarity among Sp tm tm p24 (SP24), ORF2, and other viral proteins come from homology? Significant sequence similarity is widely considered evidence of homology, because there is no imperious constraint on protein sequences that would make convergent evolution likely
Several lines of argument strongly suggest that the similarity among SP24, ORF2, and other viral proteins is due to homologous descent. (i) The region similar among ORF2 proteins is most likely globular (Fig. 3), and the caveat above does not apply. (ii) The TM segments of SP24 are predicted to carry significant evolutionary information, unlike simple “anchor” TM segments [45]. (iii) The fact that both ORF2 and ORF3 of chroparaviruses have significant similarity to those of negeviruses considerably strengthens the homology hypothesis, since it seems difficult to envision why convergent evolution would have occurred twice. (iv) There is a plausible mechanism to explain homology, i.e., horizontal transfer between similar organisms (RNA viruses) that infect similar hosts
Summary
The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. To keep the size of the data set manageable, we focused on a subset composed of proteins from viruses with positive, single-stranded RNA viral genomes and for which BLAST detected no homologs in other genera by using the parameters and database described above.
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