Evolution of increased complexity in a molecular machine

• Published in: Nature (London) Vol. 481; no. 7381; pp. 360 - 364
• Main Authors: Finnigan, Gregory C., Hanson-Smith, Victor, Stevens, Tom H., Thornton, Joseph W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-01-2012; Nature Publishing Group
• Subjects: Algorithms; Asymmetry; Biological and medical sciences; Complexity; Computational Biology; Conformational dynamics in molecular biology; Evolution; Evolution, Molecular; Extinction, Biological; Fundamental and applied biological sciences. Psychology; Fungi; Fungi - classification; Fungi - enzymology; Fungi - genetics; Gene Duplication; Genes; Genetics; Humanities and Social Sciences; letter; Models, Biological; Molecular biophysics; Molecular machines; multidisciplinary; Mutagenesis; Mutation; Phylogenetics; Phylogeny; Physiological aspects; Protein Conformation; Proteins; Reproduction; Saccharomyces cerevisiae - enzymology; Science; Science (multidisciplinary); Structure; Vacuolar Proton-Translocating ATPases - chemistry; Vacuolar Proton-Translocating ATPases - genetics; Vacuolar Proton-Translocating ATPases - metabolism; United States; Molecular evolution; Molecular assembly; Biochemical compound; Protein
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10724

Increased complexity in an essential molecular machine evolved through simple, high-probability genetic mechanisms.
Step-by-step route to complexity
In a real-life variation on the 'Jurassic Park' theme, ancestral proteins have been resurrected from synthetic DNA using sequences inferred from current versions of their genes. Finnigan
et al
. take the idea further with the reconstruction of a multiprotein complex — the transmembrane ring of the proton pump V-ATPase — using a protocol that mimics millions of years of evolution. Starting from a two-component 'ancestral' version of the protein, gene duplication and purely degenerative mutations are sufficient to trigger increased complexity in V-ATPase. Through this gradual process, the three-component complexes found in fungi and yet more elaborate equivalents in other organisms can evolve without the need for functions generated by low-probability combinations of mutations.
Many cellular processes are carried out by molecular ‘machines’—assemblies of multiple differentiated proteins that physically interact to execute biological functions
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. Despite much speculation, strong evidence of the mechanisms by which these assemblies evolved is lacking. Here we use ancestral gene resurrection
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and manipulative genetic experiments to determine how the complexity of an essential molecular machine—the hexameric transmembrane ring of the eukaryotic V-ATPase proton pump—increased hundreds of millions of years ago. We show that the ring of Fungi, which is composed of three paralogous proteins, evolved from a more ancient two-paralogue complex because of a gene duplication that was followed by loss in each daughter copy of specific interfaces by which it interacts with other ring proteins. These losses were complementary, so both copies became obligate components with restricted spatial roles in the complex. Reintroducing a single historical mutation from each paralogue lineage into the resurrected ancestral proteins is sufficient to recapitulate their asymmetric degeneration and trigger the requirement for the more elaborate three-component ring. Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.