Complex enzymes with multiple catalytic activities are hypothesized to have 
evolved from more primitive precursors. Global analysis of the Phytophthora 
sojae genome using conservative criteria for evaluation of complex proteins 
identified 273 novel multifunctional proteins that were also conserved in P. 
ramorum. Each of these proteins contains combinations of protein motifs that are 
not present in bacterial, plant, animal, or fungal genomes. A subset of these 
proteins were also identified in the two diatom genomes, but the majority of 
these proteins have formed after the split between diatoms and oomycetes. 
Documentation of multiple cases of domain fusions that are common to both 
oomycetes and diatom genomes lends additional support for the hypothesis that 
oomycetes and diatoms are monophyletic. Bifunctional proteins that catalyze two 
steps in a metabolic pathway can be used to infer the interaction of orthologous 
proteins that exist as separate entities in other genomes. We postulated that 
the novel multifunctional proteins of oomycetes could function as potential 
Rosetta Stones to identify interacting proteins of conserved metabolic and 
regulatory networks in other eukaryotic genomes. However ortholog analysis of 
each domain within our set of 273 multifunctional proteins against 39 sequenced 
bacterial and eukaryotic genomes, identified only 18 candidate Rosetta Stone 
proteins. Thus the majority of multifunctional proteins are not Rosetta Stones, 
but they may nonetheless be useful in identifying novel metabolic and regulatory 
networks in oomycetes. Phylogenetic analysis of all the enzymes in three 
pathways with one or more novel multifunctional proteins was conducted to 
determine the probable origins of individual enzymes. These analyses revealed 
multiple examples of horizontal transfer from both bacterial genomes and the 
photosynthetic endosymbiont in the ancestral genome of Stramenopiles. The 
complexity of the phylogenetic origins of these metabolic pathways and the 
paucity of Rosetta Stones relative to the total number of multifunctional 
proteins suggests that the proteome of oomycetes has few features in common with 
other Kingdoms.