Extensive Expansion of A1 Family Aspartic Proteinases in Fungi Revealed by Evolutionary Analyses of 107 Complete Eukaryotic Proteomes.

REVUELTA MV; VAN KAN JAL; KAY, J; TEN HAVE A

Genome Biology and Evolution

Oxford University Press

Año: 2014 vol. 6 p. 1480 - 1494

1759-6653

The A1 family of eukaryotic aspartic proteinases (APs) forms one of 16 aspartic proteinase families.Although one of the best characterized families, the recent increase in genome sequence data hasrevealed many fungal AP homologues with novel sequence characteristics. The present study wasperformed to explore the fungal AP sequence space and to obtain an in-depth understanding offungal AP evolution.Using a comprehensive phylogeny of ~700 AP sequences from the complete proteomes of 87 fungiand 20 non-fungal eukaryotes, eleven major clades of APs were defined of which clade I largelycorresponds to the A1A subfamily of pepsin-archetype APs. Clade II largely corresponds to the A1Bsubfamily of nepenthesin-archetype APs. Remarkably, the nine other clades contain only fungalAPs, thus indicating fungal APs have undergone a large sequence diversification. The topology ofthe tree indicates fungal APs have been subject to both ?birth and death? evolution and ´functionalredundancy and diversification´. This is substantiated by co-clustering of certain functionalsequence characteristics. A meta-analysis towards the identification of Cluster DeterminingPositions (CDPs) was performed in order to investigate the structural and biochemical basis fordiversification. Seven CDPs contribute to the secondary structure of the enzyme. Three other CDPsare found in the vicinity of the substrate binding cleft.Tree topology, the large sequence variation among fungal APs and the apparent functionaldiversification suggest that an amendment to update the current A1 AP classification based on acomprehensive phylogenetic clustering might contribute to refinement of the classification in theMEROPS peptidase database.