Abstract
Domains are the structural, functional and evolutionary units of proteins. They combine to form multidomain proteins. The evolutionary history of this molecular combinatorics has been studied with phylogenomic methods. Here, we construct networks of domain organization and explore their evolution. A time series of networks revealed two ancient waves of structural novelty arising from ancient ‘p-loop’ and ‘winged helix’ domains and a massive ‘big bang’ of domain organization. The evolutionary recruitment of domains was highly modular, hierarchical and ongoing. Domain rearrangements elicited non-random and scale-free network structure. Comparative analyses of preferential attachment, randomness and modularity showed yin-and-yang complementary transition and biphasic patterns along the structural chronology. Remarkably, the evolving networks highlighted a central evolutionary role of cofactor-supporting structures of non-ribosomal peptide synthesis pathways, likely crucial to the early development of the genetic code. Some highly modular domains featured dual response regulation in two-component signal transduction systems with DNA-binding activity linked to transcriptional regulation of responses to environmental change. Interestingly, hub domains across the evolving networks shared the historical role of DNA binding and editing, an ancient protein function in molecular evolution. Our investigation unfolds historical source-sink patterns of evolutionary recruitment that further our understanding of protein architectures and functions.
Highlights
Domains are the structural, functional and evolutionary units of proteins
We build a time series of networks of domain organization embedding evolutionary information derived from the sequence and structure of millions of protein sequences encoded in hundreds of genomes
We found that evolutionary recruitment in proteins is ongoing and highly modular
Summary
Functional and evolutionary units of proteins. They combine to form multidomain proteins. Phylogenomic trees of domain structures helped uncover the natural history of biocatalysis by tracing chemical mechanisms in enzymatic r eactions[44], analyze the optimization and increase of protein folding speed derived from a flexibility-correlated factor known as contact order (the average relative distance of amino acid contacts in the tertiary structure of proteins)[45], and study the history of an ‘elementary functionome’ with a bipartite network of elementary functional loop sequences and structural domains of p roteins[46] This last study revealed two initial waves of functional innovation involving founder ‘p-loop’ and ‘winged helix’ domain structures, and the emergence of hierarchical modularity and power law behavior in network evolution. The accumulation of architectures continued to date but with a decreasing rate[7,46]
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