title: Use of structural phylogenetic networks for classification of the ferritin-like superfamily.
abstract: In the postgenomic era, bioinformatic analysis of sequence similarity is an immensely powerful tool to gain insight into evolution and protein function. Over long evolutionary distances, however, sequence-based methods fail as the similarities become too low for phylogenetic analysis. Macromolecular structure generally appears better conserved than sequence, but clear models for how structure evolves over time are lacking. The exponential growth of three-dimensional structural information may allow novel structure-based methods to drastically extend the evolutionary time scales amenable to phylogenetics and functional classification of proteins. To this end, we analyzed 80 structures from the functionally diverse ferritin-like superfamily. Using evolutionary networks, we demonstrate that structural comparisons can delineate and discover groups of proteins beyond the "twilight zone" where sequence similarity does not allow evolutionary analysis, suggesting that considerable and useful evolutionary signal is preserved in three-dimensional structures.
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University Stockholm, 106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundin
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Poole
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Sjöberg
authors.forename: Martin
authors.initials: M
authors.lastname: Högbom
mesh_terms: D019143:Evolution, Molecular; D005293:Ferritins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D008958:Models, Molecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary
chemical_list: D005293:Ferritins