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Panorama of ancient metazoan macromolecular complexes

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ABSTRACT

Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we then generated a draft conservation map consisting of >1 million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering revealed a spectrum of conservation, ranging from ancient Eukaryal assemblies likely serving cellular housekeeping roles for at least 1 billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, by affinity-purification and by functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic significance and adaptive value to animal cell systems.

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Prevalence of conservation of protein complexes across metazoa and beyonda, Conserved multiprotein complexes, identified by clustering, arranged according to average estimated component age (see Extended Methods and ref. 25). Proteins (nodes) classified as metazoan (green) or ancient (orange); assemblies showing divergent phylogenetic trajectories termed ‘mixed’. b, Example complexes with different proportions of old and new subunits. c, Presumed origins of metazoan (new), mixed, and old complexes; ‘?’ indicates variable origins of new genes. d, Heatmap showing prevalence of selected complexes across phyla. Color reflects fraction of components with detectable orthologs (absence, dark blue). Sea anemone (N. vectensis) most distant metazoan (Cnidarian) analyzed biochemically.
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Figure 3: Prevalence of conservation of protein complexes across metazoa and beyonda, Conserved multiprotein complexes, identified by clustering, arranged according to average estimated component age (see Extended Methods and ref. 25). Proteins (nodes) classified as metazoan (green) or ancient (orange); assemblies showing divergent phylogenetic trajectories termed ‘mixed’. b, Example complexes with different proportions of old and new subunits. c, Presumed origins of metazoan (new), mixed, and old complexes; ‘?’ indicates variable origins of new genes. d, Heatmap showing prevalence of selected complexes across phyla. Color reflects fraction of components with detectable orthologs (absence, dark blue). Sea anemone (N. vectensis) most distant metazoan (Cnidarian) analyzed biochemically.

Mentions: To systematically define evolutionarily conserved functional modules, we partitioned the interaction network using a two-stage clustering procedure (Fig. 1c; see Extended Methods) that allowed proteins to participate in multiple complexes (i.e., moonlighting) as merited (Extended Data Fig. 3a). The 981 putative multiprotein groupings (Fig. 3a; see Supplementary Table 4) includes both many well-known and novel complexes linked to diverse biological processes (Extended Data Fig. 3b). The complexes have estimated component ages spanning from ~500 million (i.e., metazoan-specific, or new) to over 1 billion years (i.e., ancient, or old) of evolutionary divergence. Details of species, orthologs, taxonomic groups, protein ages and evolutionary distances are provided in Supplementary Tables 3 and 5 and Supplementary Material.


Panorama of ancient metazoan macromolecular complexes
Prevalence of conservation of protein complexes across metazoa and beyonda, Conserved multiprotein complexes, identified by clustering, arranged according to average estimated component age (see Extended Methods and ref. 25). Proteins (nodes) classified as metazoan (green) or ancient (orange); assemblies showing divergent phylogenetic trajectories termed ‘mixed’. b, Example complexes with different proportions of old and new subunits. c, Presumed origins of metazoan (new), mixed, and old complexes; ‘?’ indicates variable origins of new genes. d, Heatmap showing prevalence of selected complexes across phyla. Color reflects fraction of components with detectable orthologs (absence, dark blue). Sea anemone (N. vectensis) most distant metazoan (Cnidarian) analyzed biochemically.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5036527&req=5

Figure 3: Prevalence of conservation of protein complexes across metazoa and beyonda, Conserved multiprotein complexes, identified by clustering, arranged according to average estimated component age (see Extended Methods and ref. 25). Proteins (nodes) classified as metazoan (green) or ancient (orange); assemblies showing divergent phylogenetic trajectories termed ‘mixed’. b, Example complexes with different proportions of old and new subunits. c, Presumed origins of metazoan (new), mixed, and old complexes; ‘?’ indicates variable origins of new genes. d, Heatmap showing prevalence of selected complexes across phyla. Color reflects fraction of components with detectable orthologs (absence, dark blue). Sea anemone (N. vectensis) most distant metazoan (Cnidarian) analyzed biochemically.
Mentions: To systematically define evolutionarily conserved functional modules, we partitioned the interaction network using a two-stage clustering procedure (Fig. 1c; see Extended Methods) that allowed proteins to participate in multiple complexes (i.e., moonlighting) as merited (Extended Data Fig. 3a). The 981 putative multiprotein groupings (Fig. 3a; see Supplementary Table 4) includes both many well-known and novel complexes linked to diverse biological processes (Extended Data Fig. 3b). The complexes have estimated component ages spanning from ~500 million (i.e., metazoan-specific, or new) to over 1 billion years (i.e., ancient, or old) of evolutionary divergence. Details of species, orthologs, taxonomic groups, protein ages and evolutionary distances are provided in Supplementary Tables 3 and 5 and Supplementary Material.

View Article: PubMed Central - PubMed

ABSTRACT

Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we then generated a draft conservation map consisting of >1 million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering revealed a spectrum of conservation, ranging from ancient Eukaryal assemblies likely serving cellular housekeeping roles for at least 1 billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, by affinity-purification and by functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic significance and adaptive value to animal cell systems.

No MeSH data available.


Related in: MedlinePlus