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 ␣/␤ class being the first. Although most ancestral folds shared a common architecture of barrels or interleaved ␤-sheets and ␣-helices, many were clearly derived, such as polyhedral folds in the all-␣ class and ␤-sandwiches, ␤-propellers, and ␤-prisms in all-␤ proteins. We also describe transformation pathways of architectures that are prevalently used in nature. For example, ␤-barrels with increased curl and stagger were favored evolutionary outcomes in the all-␤ class. Interestingly, we found cases where structural change followed the ␣-to-␤ 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.

The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture

“…To decrease search times during branch swapping of suboptimal trees, no more than one tree was saved in each replicate. The tree depicted evolutionary relationships of 776 SCOP folds, was well resolved, had strong cladistic structure (P Ͻ 0.01), and was consistent with phylogenies generated from a set of 32 proteomes using a similar approach (13) . All other terminal leaves are unlabeled because they would not be legible.…”

“…Normalized fold abundance data were coded as polarized linearly ordered multistate phylogenetic characters and subjected to phylogenetic analysis using maximum parsimony as the optimality criterion in PAUP* (29). Trees were rooted without the need of external hypotheses (outgroups) by polarizing characters directly with an evolutionary model in which protein architectures that are more prevalent in nature (i.e., reused in many biological contexts) originate from innovations in structural design that occur earlier in evolutionary time (13). The ancestral condition for architectures in proteomes (popular but not necessarily widely shared) was specified by inclusion of a hypothetical ancestor in the search for optimal trees.…”

“…1). Details on the evolutionary model used in phylogenetic analysis and the validity of rooting of our phylogenomic trees (summarized in Materials and Methods) have been described, together with limita- tions and biases of the reconstruction method (13)(14)(15). There were only 16 omnipresent folds, nine of which appeared at the base of the tree.…”

“…The repertoire of architectures in proteomes can therefore be regarded as a collection of historical imprints or molecular fossils that carry considerable phylogenetic history. Using a genomic census of architecture, we recently generated phylogenies that describe the evolution of the protein world at different hierarchical levels of structural organization (13)(14)(15). These genomic-based phylogenies (phylogenomic trees) were used to classify proteins (mostly globular), define structural transformations, and uncover evolutionary patterns in structure.…”

History of biological metal utilization inferred through phylogenomic analysis of protein structures

“…Here, we expand upon this previous study by examining a larger set of elements and introduce a temporal scale. The relative timing for the evolution of metal-binding protein structures, both those exclusive and promiscuous in metal choice, was determined using a phylogeny of protein architectures that has been developed and refined over the past 7 years (18,19). The occurrences and abundances of all of the diverse Fe-, Zn-, Mn-, Co-, Ni-, Cu-, Mo-, and Ca-binding protein families in 313 genomes were also determined.…”