Diversification of the cullin family

Abstract

Background: Cullins are proteins involved in ubiquitination through their participation in multisubunit ubiquitin ligase complexes. In this study, I use comparative genomic data to establish the pattern of emergence and diversification of cullins in eukaryotes.

Results: The available data indicate that there were three cullin genes before the unikont/bikont split, which I have called Culalpha, Culbeta and Culgamma. Fungal species have quite strictly conserved these three ancestral genes, with only occasional lineage-specific duplications. On the contrary, several additional genes appeared in the animal or plant lineages. For example, the human genes Cul1, Cul2, Cul5, Cul7 and Parc all derive from the ancestral Culalpha gene. These results, together with the available functional data, suggest that three different types of ubiquitin ligase cullin-containing complexes were already present in early eukaryotic evolution: 1) SCF-like complexes with Culalpha proteins; 2) Culbeta/BTB complexes; and, 3) Complexes containing Culgamma and DDB1-like proteins. Complexes containing elongins have arisen more recently and perhaps twice independently in animals and fungi.

Conclusion: Most of the known types of cullin-containing ubiquitin ligase complexes are ancient. The available data suggest that, since the origin of eukaryotes, complex diversity has been mostly generated by combining closely related subunits, while radical innovations, giving rise to novel types of complexes, have been scarce. However, several protist groups not examined so far contain highly divergent cullins, indicating that additional types of complexes may exist.

Figure 1

Phylogenetic trees corresponding to animal cullin sequences. The figure corresponds to the NJ tree, but the MP and ML results were topologically so similar that they are also included here. Numbers in the branches refer to bootstrap support, in percentages (order: NJ/MP/ML). Numbers in brackets refer to the number of sequences within each group. Five genes (red) have been found in all animal groups. Two other (orange) are vertebrate-specific or Drosophila-specific. Details of the sequences can be found in Additional File 3.

Figure 2

Dendrogram showing the relationships among fungal cullins. Bootstrap support and number of species in the groups are indicated as in Figure 1. Details of the sequences are described in Additional File 4.

Figure 3

Dendrogram showing the relationships among fungal cullins, after eliminating the saccharomycotina species. Three highly suppported groups are apparent, which appeared before the ascomycota/basidiomycota split.

Figure 4

Dendrogram of cullin sequences obtained from bikont species. Notice the three groups in plants and stramenopiles and the multiple highly divergent groups in alveolata (pink) and excavata (blue). Bootstrap support and number of species per branch are indicated as in the previous figures (again bootstrap order: NJ/MP/ML). Details can be found in Additional File 5.

Figure 5

Phylogenetic relationships obtained for all animal and plant sequences plus sequences from pezizomycotina fungi. The three groups, corresponding to the ancestral Culα, Culβ and Culγ genes, are highly supported by the alternative methods of phylogenetic reconstruction (NJ/MP/ML). Details in Additional File 6.