Cavalier-Smith Biology Direct 2010, 5:7 http://www.biology-direct.com/content/5/1/7 RESEARCH Open Access Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution Thomas Cavalier-Smith* Abstract Background: The transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long- standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis. Results: I elucidate nuclear and mitotic coevolution, explaining the origins of dicer and small centromeric RNAs for positionally controlling centromeric heterochromatin, and how 27 major features of the cell nucleus evolved in four logical stages, making both mechanisms and selective advantages explicit: two initial stages (origin of 30 nm chromatin fibres, enabling DNA compaction; and firmer attachment of endomembranes to heterochromatin) protected DNA and nascent RNA from shearing by novel molecular motors mediating vesicle transport, division, and cytoplasmic motility. Then octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that generated the fenestrated nuclear envelope, preventing lethal complete cisternal fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC lumens by an FG-nucleoporin meshwork and adopting karyopherins for nucleocytoplasmic exchange conferred compartmentation advantages. These successive changes took place in naked growing cells, probably as indirect consequences of the origin of phagotrophy. The first eukaryote had 1-2 cilia and also walled resting cysts; I outline how encystation may have promoted the origin of meiotic sex. I also explain why many alternative ideas are inadequate. Conclusion: Nuclear pore complexes are evolutionary chimaeras of endomembrane- and mitosis-related chromatin-associated proteins. The keys to understanding eukaryogenesis are a proper phylogenetic context and understanding organelle coevolution: how innovations in one cell component caused repercussions on others. Reviewers: This article was reviewed by Anthony Poole, Gáspár Jékely and Eugene Koonin. Background associated with that membrane, and ribosomes start Cells are of only two fundamental kinds: bacteria (=pro- translating messenger RNA (mRNA) even during tran- karyotes; cells with DNA segregated by surface mem- scription. Eukaryote chromosomes are normally multiple brane motors) and eukaryotes (nucleated cells dividing and linear and never attach directly to the surface by mitosis) [1,2]. In bacteria the typically single and cir- plasma membrane. Instead they are fixed to and sur- cular DNA chromosome is attached to the surface cyto- rounded by a specialised part of the endomembrane sys- plasmic membrane and segregated by protein motors tem (the nuclear envelope, NE) during interphase, the part of the cell cycle when the cell grows, genes are * Correspondence: [email protected] transcribed, and DNA replicated. During cell division, Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK by contrast, eukaryotic chromosomes are compacted, © 2010 Cavalier-Smith; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cavalier-Smith Biology Direct 2010, 5:7 Page 2 of 78 http://www.biology-direct.com/content/5/1/7 precluding transcription or replication, and attach by selective advantages. However, the phylogenetic context their centromeres to microtubules of the mitotic spindle, has changed dramatically with our now much more which moves them into daughter cells. The problem of robust understanding of cell phylogeny (1) [3,7,8,12,13]. nuclear origins therefore requires understanding coevo- Moreover, genomics has enabled molecular origins of lution of about 27 cell components (Appendix 1) and many key eukaryotic constituents, including NPCs, to be how they became functionally interlinked into the fun- traced [14-17], whilst advances in molecular cell biology damentally novel eukaryoticlifecycle[3-5],approxi- tell us how nuclei actually assemble [18,19] and func- mately 850 My ago, at least two billion years after tion. Building on these insights, I now propose the first bacteria evolved [6]. Not only mitosis, but also sex, i.e. specific physical mechanism for evolving nuclear envel- meiosis and syngamy (cell and nuclear fusion), must ope architecture and explain its major genetic conse- have evolved at the same time. This conclusion follows quences and why other theories are inadequate. irrespective of whether the eukaryote tree is between As the field of eukaryogenesis has been confused by a unikonts (animals, fungi and three protozoan phyla) and plethora of contradictory ideas, some not compatible bikonts (plants, chromists and all other protozoan phyla with established evidence, before presenting the novel [7,8] or is instead between Euglenozoa and all other explanations I summarise two areas to put them in con- eukaryotes as shown in Fig. 1 in line with recent argu- text: (1) the phylogenetic origin of the eukaryotic com- ments for the root lying within Eozoa (Euglenozoa plus ponents, and (2) the origin of the endomembrane excavates), most likely between Euglenozoa and exca- system and cytoskeleton. I only outline the conclusions, vates sensu stricto [9]. Peroxisomes, mitochondria, cen- giving references for details, as most of the evidence and trioles, cilia, and Golgi dictyosomes must also have arguments is not new, being already published. Because originated prior to the last common ancestor of all the nature of molecular changes during major evolution- extant eukaryotes, whichever of these positions of the ary transitions is more diversified and complex than root is correct [6]. This radical transformation of cell some molecular evolutionists have realised, I also pre- structure (eukaryogenesis) is the most complex and face my original explanations of the origin of the extensive case of quantum evolution in the history of nucleus with an outline of some basic but widely life [2,3,6]. Beforehand earth was a sexless, purely bac- neglected evolutionary principles that apply to all such terial and viral world. Afterwards sexy, endoskeletal major innovations in body plan. This background is eukaryotes evolved morphological complexity: diatoms, rather long because the proper evolutionary context is butterflies, corals, whales, kelps, and trees. so important: the nucleus did not evolve on its own; Evolution of complex characters typically involves pre- explanations of its origin make no sense without under- adaptation, radical mutational innovation, and different standing the prior evolution of the endomembrane sys- selective forces acting in succession [3,6,10]. Here I tem of which its envelope is a specialised part. paint an integrated picture of how the nucleus, sex, and Intracellular coevolution of about a 100 novel properties the eukaryotic cell cycle originated and congealed into a is at the core of understanding eukaryogenesis. novel, unified, and very conservative cellular lifestyle during later stages of the conversion of a bacterium into Phylogenetic context for eukaryogenesis a eukaryote. In addition to establishing the phylogenetic Eukaryote cells are all evolutionary chimaeras of an context (Fig. 1) there are three crucial problems for ancestrally phagotrophic host cell with nucleus, endo- understanding the origin of the nucleus [5]: (1) assembly membranes, and endoskeleton [3] and an enslaved a- of endomembranes around chromatin (the DNA-histone proteobacterium converted into a mitochondrion close complex); (2) evolution of the nuclear pore complex to the time when the nucleus itself originated, i.e. prior (NPC), which crucially allows a channel between nucleo- to divergence of any extant eukaryotic lineages (Fig. 1) plasm and cytoplasm; and (3) origin of centromeres and [20]. Contrary to some assumptions [17,21], the host for mitotic spindle, without which nuclear chromosomes that symbiogenesis was not an archaebacterium, but an cannot be stably inherited. As first argued 30 years ago otherwise fully developed early eukaryote with NE and [11], origin of the cell nucleus cannot be understood in cilium (a protoeukaryote) or else an intermediate stage isolation from other major innovations of the eukaryotic (prekaryote) that had already evolved rudiments of pha- cell; intracellular coevolution among different cell con- gocytosis (the likely means of engulfing the a-proteo- stituents that interact physically or that profoundly bacterium) and internal membranes