title: An evolutionarily structured universe of protein architecture.
abstract: Protein structural diversity encompasses a finite set of architectural designs. Embedded in these topologies are evolutionary histories that we here uncover using cladistic principles and measurements of protein-fold usage and sharing. The reconstructed phylogenies are inherently rooted and depict histories of protein and proteome diversification. Proteome phylogenies showed two monophyletic sister-groups delimiting Bacteria and Archaea, and a topology rooted in Eucarya. This suggests three dramatic evolutionary events and a common ancestor with a eukaryotic-like, gene-rich, and relatively modern organization. Conversely, a general phylogeny of protein architectures showed that structural classes of globular proteins appeared early in evolution and in defined order, the alpha/beta class being the first. Although most ancestral folds shared a common architecture of barrels or interleaved beta-sheets and alpha-helices, many were clearly derived, such as polyhedral folds in the all-alpha class and beta-sandwiches, beta-propellers, and beta-prisms in all-beta proteins. We also describe transformation pathways of architectures that are prevalently used in nature. For example, beta-barrels with increased curl and stagger were favored evolutionary outcomes in the all-beta class. Interestingly, we found cases where structural change followed the alpha-to-beta tendency uncovered in the tree of architectures. Lastly, we traced the total number of enzymatic functions associated with folds in the trees and show that there is a general link between structure and enzymatic function.
authors.affiliation: Vital NRG, Knoxville, Tennessee 37919, USA. gca@uiuc.edu
authors.forename: Gustavo
authors.initials: G
authors.lastname: Caetano-Anollés
authors.forename: Derek
authors.initials: D
authors.lastname: Caetano-Anollés
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D030562:Databases, Protein / Q000706:statistics & numerical data; D004798:Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; D011506:Proteins; D020543:Proteome