  Most approaches to prediction of protein function from primary structure are
based on similarity between the query sequence and sequences of known function.
This approach, however, disregards the occurrence of gene duplication
(paralogy) or convergent evolution of the genes. The analysis of correlated
proteins that share a common domain, taking into consideration the evolutionary
history of genes under study may provide a more reliable annotation of
predicted proteins with unknown function. A computer program that enables
real-time comparison of 'gene trees' with 'species trees' was developed. The
Phylogenetic Genome Annotator (PGA) performs a profile based multiple sequence
alignment of a set of sequences that share a common domain to generate a
phylogenetic gene tree, which is compared to the species phylogeny inferred
from aligned ribossomal RNA data. The correlated protein domains are then
displayed side-by-side with the phylogeny of the corresponding species. The
statistical support of gene clusters (branches) is given by the quartet
puzzling method. This analysis readily discriminates paralogs from orthologs,
enabling the identification of proteins originated by gene duplications and the
prediction of possible functional divergence in groups of similar sequences.
The tool was tested in three distinct subfamilies of the G-protein coupled
receptor superfamily. In the analysed datasets, the paralogy prediction agreed
with the known subfamily grouping, suggesting that subfamily divergence was
facilitated by duplication events in the ancestral nodes.
