Telomeres, tethers and trypanosomes

Abstract

Temporal and spatial organization of the nucleus is critical for the control of transcription, mRNA processing and the assembly of ribosomes. This includes the occupancy of specific territories by mammalian chromosomes, the presence of subnuclear compartments such as the nucleolus and Cajal bodies and the division of chromatin between active and inactive states. These latter are commonly associated with the location of DNA within euchromatin and heterochromatin respectively; critically these distinctions arise through modifications to chromatin-associated proteins, including histones, as well as the preferential localization of heterochromatin at the nuclear periphery. Most research on nuclear organization has focused on metazoa and fungi; however, recent technical advances have made more divergent eukaryotes accessible to study, with some surprising results. For example, the organization of heterochromatin is mediated in metazoan nuclei in large part by lamins, the prototypical intermediate filament proteins. Despite the presence of heterochromatin, detected both biochemically and by EM in most eukaryotic organisms, until this year lamins were thought to be restricted to metazoan taxa, and the proteins comprising the lamina in other lineages were unknown. Recent work indicates the presence of lamin orthologs in amoeba, while trypanosomatids possess a large coiled-coil protein, NUP-1, that performs functions analogous to lamins. These data indicate that the presence of a nuclear lamina is substantially more widespread than previously thought, with major implications for the evolution of eukaryotic gene expression mechanisms. We discuss these and other recent findings on the organization of nuclei in diverse organisms, and the implications of these findings for the evolutionary origin of eukaryotes.

Figure 1. Evolutionary histories of known nuclear envelope components. (A) Cartoon of structures at, and associated with, the nuclear envelope. Shown are the nuclear pore complex/karyopherins (red), Sun/Kash (LINC complex) proteins (blue) and known components of a nuclear lamina (lamins, green; NUP-1, yellow). (B) The evolutionry distributions of the nuclear pore complex/karyopherins, Sun/Kash proteins and known nuclear lamina proteins are shown colorized and overlaid upon a schematic phylogeny of the eukaryotes, emphasizing the five contemporary-recognized supergroups. FECA, First eukaryotic common ancestor; LECA, Last eukaryotic common ancestor; KAP, karyopherin; SAR + CCTH, stramenopiles alveolates, and Rhizaria + cryptomonads, centrohelids, telonemids and haptophytes.

Figure 2. Relative sizes of metazoan and trypanosomatid nuclei and lamina monomers. Blue ovals indicate the relative sizes of a fibroblast and trypanosome nucleus, at 10 μm and 1.5 μm in diameter. The molecular weight of the unikont lamins is approximately 60 kDa while NUP-1 is 450 kDa; these are indicated as white bars close to the indicator lines for each nucleus. The inference is that the structural arrangement of the lamina in these systems is potentially very different.

Figure 3. Maximum likelihood phylogenetic tree of the SUN domains. The values supporting the separation into two main subfamilies are: approximate likelihood ratio test calculated with PhyML 3.0/non-parametric bootstrap calculated in RAxML 7.2.6/posterior probabilities from PhyloBayes 3.3b. The right panel depicts the domain structures of SUN-domain containing proteins of the representative species used in the phylogenetic analyses. Position of the SUN domain is symbolized by the blue box. Red rectangles represent hydrophobic patches predicted as transmembrane domains by TMHMM Server v. 2.0. Dashed red rectangles represent hydrophobic patches, which were not predicted as transmembrane domains. Red taxa are species where considerable characterization of the SUN proteins has been achieved.