the domain distribution includes different evolutionary information at the level of the subphyla. While the classification, based on the most common functional domains from the kinome, is very similar to the classical taxonomy it would also be interesting to try and understand the functional and evolutionary implications of the rare domains appearing only in a certain phyla or fungal species. For example, the ascomycete A. nidulans has unique domains like CNH, FAD-oxidase_C, RCC1 and many more, making a total of 16 unique accessory domains, which suggests that A. nidulans has possibly acquired a diverse kinase-related functionality. Currently, based on its physiology, there is no obvious clue as to why this should be so, but since A. nidulans is one of the beststudied model genetic species there may be a good basis to understand this result in future studies. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19796427 From the most common domain distribution, there are some clear cases of variations between the subgroups. For example the POLO_box domain appears in all Basidiomycota and in the Saccharomycotina, while is quite rare within the filamentous Ascomycota. Polo boxes appear to mediate interaction with multiple proteins through protein-protein interactions. The HEAT domain, common in both Ascomycete subphyla Pezizomycotina and Saccharomycotina, is extremely rare in Basidiomycetes. Many HEAT repeat-containing proteins are involved in intracellular transport processes. Although we cannot fully understand how these differences directly impact the function of the different species, there is a clear correlation between the domain distributions and the taxonomic classification. Conclusions The overall distribution of protein kinases within very different fungal phyla and subphyla seems to be very similar. The overall kinome density is in good agreement with taxonomy. The distribution of additional domains, which could have functional implications, does differ significantly between species, and seems able to provide a functional classification that overlaps with taxonomical classification. Although generally the classical phyla classification correlates with the kinome density and domain distribution, 
there are exceptions. Basidiomycota do not cluster by kinase number, but they have a similar kinome to proteome ratio. MedChemExpress EW-7197 ascomycetes are well clustered by all criteria, with two exceptions: A. nidulans has a different kinome to proteome ratio and a different kinase distribution. Nevertheless, A. nidulans is not unusual according to the PCA analysis. Among the filamentous ascomycetes, there is no obvious clustering according to class within the subphylum Pezizomycotina. We note, however, that the class Eurotiomycetes is over-represented in the sequenced genomes published to date, perhaps because the beneficial, harmful, or pathogenic members of this group, which have drawn much attention over the years. Schizosaccharomyces pombe has a very high kinome density much similar to the Saccharomycotina group. The predicted proteome of Laccaria bicolor has an extraordinary number of TKL kinases; further work can determine whether this is an anomaly, or a more general trait found in mycorrhizal symbionts. Finally, the PCA approach based on the most common domains clusters the Pezizomycotina group and the Saccaromycotina group very tightly, while the Basidiomycetes are more divergent. The approach taken here could be repeated for additional groups of proteins in order to study their evolution and variability wi