Comparison of sequence-based and structure-based phylogenetic trees of homologous proteins: Inferences on protein evolution

Abstract

Several studies based on the known three-dimensional (3-D) structures of proteins show that two homologous proteins with insignificant sequence similarity could adopt a common fold and may perform same or similar biochemical functions. Hence, it is appropriate to use similarities in 3-D structure of proteins rather than the amino acid sequence similarities in modelling evolution of distantly related proteins. Here we present an assessment of using 3-D structures in modelling evolution of homologous proteins. Using a dataset of 108 protein domain families of known structures with at least 10 members per family we present a comparison of extent of structural and sequence dissimilarities among pairs of proteins which are inputs into the construction of phylogenetic trees. We find that correlation between the structure-based dissimilarity measures and the sequence-based dissimilarity measures is usually good if the sequence similarity among the homologues is about 30% or more. For protein families with low sequence similarity among the members, the correlation coefficient between the sequence-based and the structure-based dissimilarities are poor. In these cases the structure-based dendrogram clusters proteins with most similar biochemical functional properties better than the sequence-similarity based dendrogram. In multi-domain protein families and disulphide-rich protein families the correlation coefficient for the match of sequence-based and structure-based dissimilarity (SDM) measures can be poor though the sequence identity could be higher than 30%. Hence it is suggested that protein evolution is best modelled using 3-D structures if the sequence similarities (SSM) of the homologues are very low.

Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability

“…4). 3D structure-based evolution analysis is well established 27 and has been shown to be more robust than to sequence-based analyses where the sequence similarity is limited, since the structure directly determines biological functions 28 . Given that the sequence similarities of the flaviviruses from different groups are relatively low (<40%), we performed a structure-based phylogeny, which suggests that encephalitic flaviruses (JEV group) are more structurally similar than are dengue viruses (DENV group), interestingly, ZIKV links the JEV and DENV groups and is more similar to the JEV group (Fig.…”

Analysis of proteins with the 'hot dog' fold: Prediction of function and identification of catalytic residues of hypothetical proteins

“…Pairwise structural superposition of the monomers and dimers was carried out using DaliLite. These results are used to calculate the structural distance measure (SDM) [ 48 , 49 ]. SDM values are calculated based on structural superposition and thus provide a better model for the evolutionary relation of proteins with very low sequence identities.…”

UPF201 Archaeal Specific Family Members Reveal Structural Similarity to RNA-Binding Proteins but Low Likelihood for RNA-Binding Function

“…While the structural divergence exponentially decreases as the sequence similarity increases, the same is not true when then the sequence similarity is below 25% or so. Moreover, tertiary structures tend to be more conserved in evolution and retain the functional properties than sequences [60], [61]. Accordingly, the structure based phylogenetic tree is more informative than that based on sequence (Figure 3a and 3b).…”