Discovery and Analysis of Repeat and Low-Complexity Architectures in Proteins and Their Conserved Evolutionary Relationships Using Self-Homology Dot Plots.

Proteins that contain sequence repetitions and low complexity regions can be analyzed using self-homology dot plot analysis. Dot plots can readily identify protein sequence repeats; the number of repeats and their length and location within the protein sequence are readily identifiable from the dot plots without the need to pre-define any of these attributes, making this method largely model-independent. We discuss the criteria for statistical identification of protein repeats and recommend simple ways of identifying protein repeats. While higher levels of sequence conservation within the repeats do make them easier to formally identify, this method can identify protein repeats with fairly low levels of conservation, as well as notably non-tandem repetitions with sizeable sections of complex, non-repeat sequence separating the individual repeat instances. Furthermore, even simple visual examination of these dot plots can discover conserved patterns within families of closely related proteins, and the level of this conservation can be readily quantified using a Jaccard index. Exhaustive pairwise comparisons can be assembled using hierarchical clustering methods to get a picture of the conserved repeat architectures within families of repeat proteins.