Extended Data Figure 10: Proposed evolutionary origin of the NPC from a later amalgam of membrane coating complexes.

a, Diagram depicting how the NPC may have originated from an ancestral coatomer module through a series of duplications, divergence and secondary loss events. Top, the origin of an ancestral proto-NPC coatomer module from an amalgamation of COPI-like and COPII-like complexes. Middle, the initial duplication leading to the origin of the inner and outer rings, and their associated coiled bundles. Presumed secondary losses removed the additional COPII-like subunit of the inner-ring protomer; loss of the adaptin-like subunit from the outer ring may have occurred here, or later in only certain lineages. Bottom, another duplication and divergence within each spoke may then have generated two parallel and laterally-offset paralogous columns; in the outer ring, a COPII-like subunit was then lost from one of the duplicates. The coiled bundles of the outer rings gave rise to the cytoplasmic export complex and nuclear basket by subsequent duplication; the export complex itself is a duplicate with a dimer of trimeric coiled bundles in its core. Outer-ring duplications are not shown. Relevant nucleoporin domains are depicted as follows: β-propellers (cyan circles), α-solenoids (pink bars) and coiled-coil domains (orange sticks). Left, diagrams (grey) exemplify the path of duplications within the whole NPC. Examples of ribbon representations for each module are presented. The anchoring points of the coiled-coil cytoplasmic Nup82 complex and the nuclear basket (orange densities) into an equivalent region of the outer-ring Nup84 complex (grey density) are shown. b, Conserved structural motifs connecting spokes in the outer and inner rings. Diagram showing how the spoke-to-spoke connection is established through similar head-to-head connections of heterodimers containing one COPI-like and one COPII-like subunits in both the outer (left) and the inner (right) NPC rings. Top, nucleoporin domains coloured as in a; bottom, COPI-like Nups in red, COPII-like Nups in blue.