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Panorama of ancient metazoan macromolecular complexes

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.


Derivation of complexesa, The 2,153 proteins present in the 981 derived metazoan complexes participate in multiple assemblies (‘moonlighting’) to an extent comparable to the sharing of subunits reported for literature-derived complexes (CORUM). For comparison, we examined the 1,550 unique proteins from the full CORUM set of 1,216 human complexes passing our selection criteria for supporting evidence (‘Unmerged’) and the 1,461 unique proteins from the non-redundant set of 501 merged complexes used as the reference for splitting our training and testing sets, with some of the largest complexes removed to avoid bias in training (‘Merged’; see ‘Optimizing the two-stage clustering’ in Extended Methods for details). b, Schematic of 981 identified complexes containing 2,153 unique proteins. In this graphical representation, 7,669 co-complex interactions are shown as lines, and proteins as nodes. Red and green interactions were previously annotated in CORUM. Red interactions were used in training the classifier and/or clustering procedure, while green interactions were held out for validation purposes. Gray interactions were not previously annotated in CORUM.
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Figure 8: Derivation of complexesa, The 2,153 proteins present in the 981 derived metazoan complexes participate in multiple assemblies (‘moonlighting’) to an extent comparable to the sharing of subunits reported for literature-derived complexes (CORUM). For comparison, we examined the 1,550 unique proteins from the full CORUM set of 1,216 human complexes passing our selection criteria for supporting evidence (‘Unmerged’) and the 1,461 unique proteins from the non-redundant set of 501 merged complexes used as the reference for splitting our training and testing sets, with some of the largest complexes removed to avoid bias in training (‘Merged’; see ‘Optimizing the two-stage clustering’ in Extended Methods for details). b, Schematic of 981 identified complexes containing 2,153 unique proteins. In this graphical representation, 7,669 co-complex interactions are shown as lines, and proteins as nodes. Red and green interactions were previously annotated in CORUM. Red interactions were used in training the classifier and/or clustering procedure, while green interactions were held out for validation purposes. Gray interactions were not previously annotated in CORUM.

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
Derivation of complexesa, The 2,153 proteins present in the 981 derived metazoan complexes participate in multiple assemblies (‘moonlighting’) to an extent comparable to the sharing of subunits reported for literature-derived complexes (CORUM). For comparison, we examined the 1,550 unique proteins from the full CORUM set of 1,216 human complexes passing our selection criteria for supporting evidence (‘Unmerged’) and the 1,461 unique proteins from the non-redundant set of 501 merged complexes used as the reference for splitting our training and testing sets, with some of the largest complexes removed to avoid bias in training (‘Merged’; see ‘Optimizing the two-stage clustering’ in Extended Methods for details). b, Schematic of 981 identified complexes containing 2,153 unique proteins. In this graphical representation, 7,669 co-complex interactions are shown as lines, and proteins as nodes. Red and green interactions were previously annotated in CORUM. Red interactions were used in training the classifier and/or clustering procedure, while green interactions were held out for validation purposes. Gray interactions were not previously annotated in CORUM.
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Figure 8: Derivation of complexesa, The 2,153 proteins present in the 981 derived metazoan complexes participate in multiple assemblies (‘moonlighting’) to an extent comparable to the sharing of subunits reported for literature-derived complexes (CORUM). For comparison, we examined the 1,550 unique proteins from the full CORUM set of 1,216 human complexes passing our selection criteria for supporting evidence (‘Unmerged’) and the 1,461 unique proteins from the non-redundant set of 501 merged complexes used as the reference for splitting our training and testing sets, with some of the largest complexes removed to avoid bias in training (‘Merged’; see ‘Optimizing the two-stage clustering’ in Extended Methods for details). b, Schematic of 981 identified complexes containing 2,153 unique proteins. In this graphical representation, 7,669 co-complex interactions are shown as lines, and proteins as nodes. Red and green interactions were previously annotated in CORUM. Red interactions were used in training the classifier and/or clustering procedure, while green interactions were held out for validation purposes. Gray interactions were not previously annotated in CORUM.
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.