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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.

No MeSH data available.


Properties of new and old proteins and complexesa, The 2,153 protein components in the conserved animal complexes tend to be more ancient than the 2,301 proteins reported in the CORUM reference complexes or in two recent large-scale protein interaction assays, based on either the 7,062 proteins found by affinity purification/mass spectrometry (AP/MS; BioGrid 166968, Huttlin EL (2014/pre-pub), downloaded Feb 10th 2015) or the 3,667 proteins analyzed by yeast two-hybrid assays (Y2H)10. Ages are derived from OMA as in ref. 25. b, Annotation rates (mean count of annotation terms per protein) of old and new proteins in the derived complexes and pairwise PPI, compared with proteins in the CORUM reference complex set. Old proteins (defined by OMA) from the complexes generally exhibited higher annotation rates than new proteins. c, Differential enrichment of old, mixed and metazoan-specific protein complexes for functional annotations (select GO-slim biological process terms shown, top) and protein domains (Pfam, bottom).
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Figure 9: Properties of new and old proteins and complexesa, The 2,153 protein components in the conserved animal complexes tend to be more ancient than the 2,301 proteins reported in the CORUM reference complexes or in two recent large-scale protein interaction assays, based on either the 7,062 proteins found by affinity purification/mass spectrometry (AP/MS; BioGrid 166968, Huttlin EL (2014/pre-pub), downloaded Feb 10th 2015) or the 3,667 proteins analyzed by yeast two-hybrid assays (Y2H)10. Ages are derived from OMA as in ref. 25. b, Annotation rates (mean count of annotation terms per protein) of old and new proteins in the derived complexes and pairwise PPI, compared with proteins in the CORUM reference complex set. Old proteins (defined by OMA) from the complexes generally exhibited higher annotation rates than new proteins. c, Differential enrichment of old, mixed and metazoan-specific protein complexes for functional annotations (select GO-slim biological process terms shown, top) and protein domains (Pfam, bottom).

Mentions: Strikingly, although proteins arising in metazoa (i.e. by gene duplication or other means) account for ~3/4 of all human gene products, they form only ~1/3 (39%; 147) of the clusters (Fig. 3a). These ‘new’ complexes tend to be smaller (i.e., ≤3 components; Fig. 3b) and specific (i.e., components not present in ‘mixed’ complexes). This indicates that although protein number and diversity greatly increased with the rise of animals25, most stable protein complexes were inherited from the unicellular ancestor and subsequently modified slightly over time (Fig. 3c and Supplementary Table 5). Indeed, the dominant phylogenetic profile of complexes across Eukarya (Fig. 3d) is composed either entirely (344 ‘old’ complexes) or predominantly (490 ‘mixed’ complexes) of ancient subunits ubiquitous among eukaryotes (Extended Data Fig. 4a; see Supplementary Table 5 for details), the latter presumably reflecting preferential accretion of new components to pre-existing macromolecules (Fig. 3c)28.


Panorama of ancient metazoan macromolecular complexes
Properties of new and old proteins and complexesa, The 2,153 protein components in the conserved animal complexes tend to be more ancient than the 2,301 proteins reported in the CORUM reference complexes or in two recent large-scale protein interaction assays, based on either the 7,062 proteins found by affinity purification/mass spectrometry (AP/MS; BioGrid 166968, Huttlin EL (2014/pre-pub), downloaded Feb 10th 2015) or the 3,667 proteins analyzed by yeast two-hybrid assays (Y2H)10. Ages are derived from OMA as in ref. 25. b, Annotation rates (mean count of annotation terms per protein) of old and new proteins in the derived complexes and pairwise PPI, compared with proteins in the CORUM reference complex set. Old proteins (defined by OMA) from the complexes generally exhibited higher annotation rates than new proteins. c, Differential enrichment of old, mixed and metazoan-specific protein complexes for functional annotations (select GO-slim biological process terms shown, top) and protein domains (Pfam, bottom).
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Figure 9: Properties of new and old proteins and complexesa, The 2,153 protein components in the conserved animal complexes tend to be more ancient than the 2,301 proteins reported in the CORUM reference complexes or in two recent large-scale protein interaction assays, based on either the 7,062 proteins found by affinity purification/mass spectrometry (AP/MS; BioGrid 166968, Huttlin EL (2014/pre-pub), downloaded Feb 10th 2015) or the 3,667 proteins analyzed by yeast two-hybrid assays (Y2H)10. Ages are derived from OMA as in ref. 25. b, Annotation rates (mean count of annotation terms per protein) of old and new proteins in the derived complexes and pairwise PPI, compared with proteins in the CORUM reference complex set. Old proteins (defined by OMA) from the complexes generally exhibited higher annotation rates than new proteins. c, Differential enrichment of old, mixed and metazoan-specific protein complexes for functional annotations (select GO-slim biological process terms shown, top) and protein domains (Pfam, bottom).
Mentions: Strikingly, although proteins arising in metazoa (i.e. by gene duplication or other means) account for ~3/4 of all human gene products, they form only ~1/3 (39%; 147) of the clusters (Fig. 3a). These ‘new’ complexes tend to be smaller (i.e., ≤3 components; Fig. 3b) and specific (i.e., components not present in ‘mixed’ complexes). This indicates that although protein number and diversity greatly increased with the rise of animals25, most stable protein complexes were inherited from the unicellular ancestor and subsequently modified slightly over time (Fig. 3c and Supplementary Table 5). Indeed, the dominant phylogenetic profile of complexes across Eukarya (Fig. 3d) is composed either entirely (344 ‘old’ complexes) or predominantly (490 ‘mixed’ complexes) of ancient subunits ubiquitous among eukaryotes (Extended Data Fig. 4a; see Supplementary Table 5 for details), the latter presumably reflecting preferential accretion of new components to pre-existing macromolecules (Fig. 3c)28.

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.