Evolution and diversification of the nuclear pore complex

Abstract

The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically composed of over 300 polypeptides, the NPC shares evolutionary origins with endo-membrane and intraflagellar transport system complexes. The modern NPC was fully established by the time of the last eukaryotic common ancestor and, hence, prior to eukaryote diversification. Despite the complexity, the NPC structure is surprisingly flexible with considerable variation between lineages. Here, we review diversification of the NPC in major taxa in view of recent advances in genomic and structural characterisation of plant, protist and nucleomorph NPCs and discuss the implications for NPC evolution. Furthermore, we highlight these changes in the context of mRNA export and consider how this process may have influenced NPC diversity. We reveal the NPC as a platform for continual evolution and adaptation.

Keywords: eukaryogenesis; evolutionary biology; nuclear pores; nuclear protein transport.

Figure 1.. Evolutionary origins of the NPC.

(A) Protocoatomer hypothesis states that a single protocoatomer (left, dark purple line) originated sometime early in eukaryotic evolution and gave rise to the two major coat protein families — type I (red lines) and type II (blue lines). Type I and type II coat proteins jointly formed the Proto-NPC — progenitor of the LECA NPC (right) — the concentric assembly of octagonally symmetric inner (IR, purple and dark blue), outer (OR, orange) and membrane (MR, beige) rings anchored in the NE pore that houses the nuclear basket (light blue), the cytoplasmic export platform (pink and burgundy) and FG-repeat nucleoporins (green). (B) An assembly of type I and II coat proteins formed an NPC protomer that populated the double inner ring via oligomerisation and stoichiometric duplication, and further — via paralogous duplication — the outer rings of LECA NPC. (C) Further diversification post-LECA gave rise to many NPC architectures in major taxa of eukaryotic tree (top) that principally differ in the stoichiometry and symmetry of outer cytoplasmic and nucleoplasmic rings (CR and NR), the manner of outer ring attachment to the inner rings and presence and symmetry of specific FG-nup and MR elements.

Figure 2.. Comparisons of nucleoporins across species in selected taxa.

Data collated for H. Sapiens [8], S. cerevisiae [10], S. pombe [12], C. thermophilum [14], C. reinhardtii [17], A. thaliana [18], M. domestica [19], T. thermophila [20], T. brucei [21] species and Chlorarachniophytes and Cryptophyceae species clades [125]. Nucleoporins are listed according to their complex and ring disposition in NPC compartments: the inner ring (IR), outer cytoplasmic and nucleoplasmic rings (CR and NR), membrane ring (Mem. Ring, MR), cytoplasmic filaments (Cyt. Filaments, CF) and nuclear basket (Nuc. Basket, NB). Nucleoporins are additionally coloured by type: FG-nups and linker FG-nups in IR, CR and NR, CF and NB in swamp green; Nup93/Nic96 complex core in IR in blue; core IR scaffold Nups in purple (also present in ORs as connector Nups); OR Nups in orange; pore membrane proteins (POMs) in MR in beige; Cytoplasmic Export platform scaffold in CF in pink; mRNP Remodelling in CF in burgundy, and basket scaffold Nups in NB in light blue. Each row represents an orthologous nucleoporin group. Nucleoporins absent in an organism are indicated by a dash (-). In cases of paralogous duplication within an organism — multiple nucleoporins are listed in square brackets, i.e. [ScNup167 ScNup170]. Alternative nucleoporin names are listed in round brackets, i.e. HsNup42 (HshCG1). Ring stoichiometry noted for IR and ORs. Exclusive Y-complex component distribution in S. pombe is additionally indicated by colour: red for CR-specific and blue for NR-specific. Macronuclei/micronuclei- (MAC-/MIC-) specificity for nucleoporins in Tetrahymena is denoted by Mac- or Mic-prefixes in gene names or * and ** for POMs. Trypanosoma-specific Multi-Complex FG-Nup and Nup76 complexes are shown by additional brackets. In ‘architecture’ column (left) given are the schematic protein fold architectures common for the orthologous Nup groups. Additional unique architectures are indicated for TbNup65 that sports a trans-membrane helix uniquely in its orthologous group (demonstrated on the right), and for lineage-specific Nups TtPOM82, TtNup185, TbNup64, TbNup75, TbNup98, TbNup140 and TbNup149.

Figure 3.. mRNA export machinery evolution.

(A) Schematic summarising interactions and participants in the global RNA-independent mRNA export machinery. Nascent mRNA complexes with THO/TREX and after displacement of UAP56, export factor Nxf1 is recruited. mRNP is delivered to TREX-2 which facilitates the entry to the NPC. Nxf1 interacts with FG-repeats along the NPC and components at the cytoplasmic face catalyse the release of mRNA. (B) TREX and TREX-2 complexes, export factors, nuclear basket and cytoplasmic NPC components across taxa are summarised. Compared components are shown on the left, depicted with small coloured circles. All the experimental characterised components are written. With a dash, components are certainly absent, dotted circles, components identified in silico, but not experimentally characterised yet. Components marked with a double black star have been identified, but participation in mRNA export has not been proven. n.i. component not identified yet.

Figure 4.. Outstanding questions in NPC evolution and known NPC diversifications.

(A) While the structural core of LECA NPC — its inner and outer rings — can be convincingly traced to type I and type II coat proteins (left), it is yet unclear how the NPC acquired its other components — responsible for mRNA processing and general permselective function (right). As individual FG-nups/transport factor combinations were shown sufficient to execute partial per-selective function, and POMs — to form pores in lipid bilayers, the possibility arises that these components formed a separate simple pore before incorporation into NPC. (B) Summary of principal variations and evolutionary events in NPC architectures post-LECA. Principal architectural changes are named for each compartment. Principal evolutionary events are named and indicated. Paralogous duplication events indicated by a — a,b pairs with slight colour change. Gene loss — by dashed lines and letters. Gene gain — by a — c pairs and colour change. Changes in stoichiometry — shown schematically. Principal complex gains are named.