RESEARCH HIGHLIGHTS

SYSTEMS BIOLOGY Ancient protein complexes revealed

A systematic analysis of protein-complex history, they applied the approach to eight some interesting conclusions. For example, composition across a billion years of evo- species—mouse, frog, fly, worm, sea urchin, despite the fact that the majority of human lution reveals a spectrum of conservation. sea anemone, amoeba and yeast—spanning proteins arose in animals, they found that by Comparative analyses of protein-protein a billion years of evolution. and large, most stable human protein com- interaction networks from Escherichia coli to With this massive set of experiments, the plexes were likely inherited from a unicellular humans have shown that such networks are researchers identified and quantified 13,386 ancestor. Membership in such ancient com- conserved and relatively slow-evolving. Yet protein orthologues. They developed a plexes was either conserved or mixed with open questions remain about whether physi- machine learning–classification method to animal-specific components, and these com- cal interactions are preserved between evolu- pull out interactions that were conserved plexes tended to be abundant, ubiquitously tionarily distinct species, what these protein between human proteins and their worm, expressed and functionally associated with complexes are and what they do. fly, mouse and sea urchin orthologues (the core cellular processes. The relatively rare These are some of the questions that data from the other four species were used complexes consisting solely of proteins that Andrew Emili of the University of Toronto, to benchmark the approach). Their final net- arose in animals, in contrast, tended to have Edward Marcotte of the University of Texas at work contained 16,655 human co-complex functions strongly linked to multicellularity. Austin and their colleagues set out to answer. interactions with supporting evidence from The team’s draft protein-complex conser- In a previous study, the team developed a at least two other species. vation map is available at http://metazoa. standardized approach to determine protein Next, the team used these results to pre- med.utoronto.ca and should suggest inter- membership in soluble human complexes, dict co-complex interactions between esting avenues for future analysis. using biochemical fractionation followed by orthologous protein pairs for an additional Allison Doerr mass spectrometry. In their new work, seek- 122 eukaryotes, some of which they validated RESEARCH PAPERS ing to discover which of the human protein using affinity purification coupled with mass Wan, C. et al. Panorama of ancient metazoan macro- complexes had been conserved throughout spectrometry. Clustering analysis led to molecular complexes. Nature 525, 339–344 (2015). Nature America, Inc. All rights reserved. America, Inc. © 201 5 Nature npg

NATURE METHODS | VOL.12 NO.11 | NOVEMBER 2015 | 1011