Cells from eukaryotic organisms (e.g. Animals, Plants, Fungi, Protists) differ from those of the prokaryotes (Bacteria and Archaea) in a large number of characteristics. These differences are so vast that the evolution of the eukaryotic cell from prokaryotic ancestors is widely regarded as a major evolutionary discontinuity.[1,2] Although there are no clear intermediates in this transition, the available evidence strongly indicates that eukaryotic cells have evolved much later (only about 1-1.5 billion years ago) in comparison to the prokaryotic organisms, which existed as far back as 3.5-3.8 Ga ago. The question thus arises how did the transition from prokaryotic to eukaryotic cell come about and who are the progenitors of the ancestral eukaryotic cell?
Analyses of molecular sequences in the past 10-12 years have provided strong evidence that all eukaryotic cells possess large number of genes (representing significant portions of their genomes) that exhibit greater similarity to either Archaea or Bacteria.[5-11] In general, eukaryotic genes for information transfer processes are more closely related to Archaea, whereas those encoding metabolic processes appear to be primarily derived from Bacteria. [5,8,9,12] These results provide strong evidence against a sister-group relationship between Archaea and Eukaryotes and the origin of the eukaryotic cell directly from an archaebacterial ancestor. To account for the unique genotype and phenotype of eukaryotic cells, several hypotheses have been proposed. [4,6,8,13-19] However, the most widely accepted proposals postulate that the fusion or association of distinct bacterial and archaealpartners lead to the origin of eukaryotic cell [4,6,8,11,16-18].
Similarity Between Mitochondria and Bacteria
Protein Signature Indicating the Origin of Plastids from Cyanobacteria (Click to enlarge)
The pioneering work of Margulis in the 1960’s strongly indicated that a number of eukaryotic cell organelles such as mitochondria and plastids originated from bacteria via endosymbiosis.[20-22] The endosymbiotic origin of mitochondria from an alpha proteobacteria and plastids from cyanobacteria is now firmly established based on molecular sequence data and other characteristics. [21-23] In view of the established origin of mitochondria from bacteria, the central question concerning the origin of the eukaryotic cell is when and how various other characteristics, which define a eukaryotic cell (e.g. nucleus, ER, cytoskeleton, etc.) have originated. Some authors have suggested the existence of hypothetical proto-eukaryotic organisms possessing such characteristics, which later engulfed either an Archaea or both an Archaea and Bacteria to give rise to eukaryotic cells.[14,24] However, these hypotheses invoke hypothetical entities for which there exists no evidence. The two main kinds of proposals that have been put forward to explain the origin of these characteristics both contend that they have originated as a result of symbiotic association or fusion between different groups of prokaryotes. However, these two sets of proposals differ from each other in one very important respect. The first set of proposals contend that an ancestral cell which contained various eukaryotic characteristics such as the nucleus, ER and cytoskeleton, etc evolved first as a result of a primary fusion and integration of specific bacterial and archaeal partners. This nucleated cell then served as a host for the subsequent endosymbiotic event leading to the origin of mitochondria (“nucleus first-mitochondria later models”).[6,8,17-19,25] In contrast, the second set of proposals, suggested later, postulate that all of the eukaryotic cell characteristics including the nucleus, ER and cytoskeleton as well as mitochondria, are the result of a single symbiotic event involving a bacterial and an archaeal cell i.e. “mitochondria-nucleus co-origin models”.[16,26,27]
The main impetus for “mitochondria-nucleus co-origin” proposals has come from the observations that a number of protist lineages (e.g., Diplomonads, Metamonada, Microsporidia and Parabasalia), which were originally believed to lack mitochondria, have now been found to contain at least a few genes that appear to be mitochondria-related.[16,29,30] These observations, in conjunction with the finding that some anaerobic protist lineages contain a mitochondria-related organelle hydrogenosome (which releases gaseous hydrogen), has led to the so called ‘hydrogen hypothesis’ of eukaryotic cell formation. According to this hypothesis, the ancestral eukaryotic cell arose as a result of syntrophic association between a hydrogen-dependent archaebacterium (a methanogen) and an α-proteobacterium, which under anaerobic conditions produced molecular hydrogen as a waste product. This syntrophy caused the engulfment of the α-proteobacterium by the archaeal partner, which led to the formation of both mitochondria as well as all other eukaryotic cell characteristics.
Although “mitochondria-nucleus co-origin” proposals may appear to be the most parsimonious way to account for the presence of both mitochondria or at least some mitochondrial genes in different eukaryotes, it offers no explanation of how any of the main characteristics that define a eukaryotic cell (nucleus, endoplasmic reticulum (ER)) evolved. A number of other observations also call into question the validity of these proposals.[6,31] These include: (i) Based on the widespread association between methanogenic archaea and hydrogen-producing proteobacteria, it is difficult to understand why the formation of eukaryotic-like cells was a unique event and it did not occur independently on multiple occasions. (ii) In all established cases of endosymbiosis (e.g. formation of mitochondria and plastids) the metabolic processes which formed the basis of symbiosis have been retained by the resultant organisms. Yet, eukaryotes have not retained any genes for methanogenesis, which is the proposed basis of their origin by these proposals. (iii) There is now strong evidence that proteobacteria (α or δ), which comprise the bacterial partner in this symbiotic event, have evolved much later than cyanobacteria. This finding implies that formation of the ancestral eukaryotic cell took place in an aerobic atmosphere. The proposed symbiosis between an anaerobic hydrogen-producing bacterium and a strictly anaerobic methanogenic archaebacterium should lead to formation of an anaerobic organism, which is expected to be at a great selective disadvantage in the oxygenic atmosphere. (iv) These proposals provides no explanation why eukaryotic genes for information transfer processes are derived from the archaeal partner.[7-9] (v) Molecular sequence data indicate that thermoacidophilic archaea rather than methanogens are the closest relatives of eukaryotes.[6,33]
Gupta and coworkers have developed a detailed proposal for the “nucleus-first, mitochondria-later” origin of the eukaryotic cells based on their work with the Hsp70 and Hsp90 family of proteins.[6,8,25,34-36] Distinct homologs of Hsp70 and Hsp90 encoded by different genes are present in mitochondria, cytosol and ER compartments.[6,25,35] The mitochondrial and hydrogenosomal homologs of the Hsp70 are clearly derived from α- proteobacteria as evidenced by phylogenetic analyses and many common signature sequences.[6,25,35] However, the homologs of Hsp70 which are present in the cytosolic and ER compartments, although they are also derived from bacteria, show no relationship to mitochondrial homologs.[6,8,25] These nuclear-cytosolic homologs contain a large number of “uniquely eukaryotic” signatures that are not present in any mitochondrial, hydrogenosomal or prokaryotic homologs, indicating that they have originated independently of these organelles. [6,8,25] The analyses of Hsp70 and Hsp90 family of proteins also show that ER and cytosolic homologs of these proteins are the results of gene duplication events that occurred at a very early stage in the formation of the eukaryotic cell.[25,37] Since the ER forms the nuclear envelope, an understanding of the events leading to the origin of genes/proteins in this compartment is of central importance for understanding the origin of the eukaryotic cell.
The Hsp70 and Hsp90 family of proteins both comprise major molecular chaperone proteins, which play pivotal roles in the transport of other proteins and molecules across cellular membranes. Gupta and coworkers have proposed that the ancestral eukaryotic cell (lacking mitochondria) evolved as a result of symbiotic association between a Gram-negative bacteria (related to proteobacteria) and an Archaea (most likely belonging to the Crenarachaeota or Eocyte group).[6,8,31] This proposal explains why the Hsp70 and Hsp90 genes were duplicated at an early stage in the evolution of the eukaryotic cell, and account for the fact that their nuclear cytosolic counterparts are derived from a bacterial ancestor other than the one that gave rise to mitochondria. This symbiosis is postulated to have developed in an oxygenic environment that was predominated by antibiotic producing organisms. A combination of these two major selective forces (oxygen and antibiotics sensitivity) led to the association of an antibiotic-resistant and oxygen-sensitive archaea with an oxygen-tolerant (or utilizing) and antibiotic-sensitive bacterium, which provided mutual protection to both in this environment.[6,31] This association led to the envelopment of the archaea by membrane infolds from the bacterial partner to shield it from oxygen. Under these conditions, the cell membrane of the archaea became redundant and was eventually lost. At a later stage, the membrane infolds surrounding the archaea were separated from the bacterial membrane. This led to the formation of the endomembrane system (or the ER) as well as the nucleus of the ancestral eukaryotic cell. Since this newly formed compartment (i.e. ER) had to communicate (i.e. import/export proteins and other molecules) with the rest of the cell, its formation was accompanied or preceded by duplication of the genes for the Hsp70 and Hsp90 chaperones, which are required for protein transport across different compartments.[25,37] The formation of this new cell was accompanied by selection of genes from the two parents. During this process, most of the genes for the information transfer processes (which provide the main targets for antibiotics) were retained from the archaea, whereas those for the metabolic processes were predominantly from the bacterial partner.[6,31] The transfer of all of these genes into the newly formed nuclear compartment completed the integration (or primary fusion) of the original symbionts into a new type of cell, which later served as a host for the endosymbiotic event leading to the development of mitochondria.
In addition to the above model, a number of other variations of the nucleus-first and mitochondria-later proposal have been proposed to account for specific characteristics of eukaryotic cells. To account for the origin of eukaryotic motility machinery (microtubule based), Margulis and coworkers have suggested that the ancestral eukaryotic cell was formed by the association of a motile sulfide-oxidizing spirochete bacteria with a sulfur-reducing Thermoplasma (Archaebacteria).[18,38] Although this proposal is noteworthy because of its attempt to explain the origin of the eukaryotic cytoskeleton and motility (tubulin based), its main drawback is that there is no evidence indicating that any of the genes in eukaryotic cells, including those for the motility functions, are derived from spirochetes.6 Recently, Jenkins et al. have identified a tubulin-related protein in Prosthecobacter, but the possible origin of this gene/protein in this bacterium is unclear. Lake and Rivera  and Horiike et al. have suggested that the nucleus is an endosymbiont which arose from the engulfment of an archaea (or Crenarchaeota) by a Gram-negative bacterium. However, the main difficulty with these models is that the nucleus is not an endosymbiont in the same sense as mitochondria or plastids, which have retained their information transfer machinery and are specifically related to their parental lineages.[21,23]
Based upon the available evidence, it is thus clear that the formation of the ancestral eukaryotic cell constituted an evolutionary discontinuity that involved fusion of different groups of prokaryotes. However, given the unique and highly unusual nature of this fusion event, a clear understanding as to how the ancestral eukaryotic cell and its different unique characteristics originated remains to be achieved.
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Bacterial (Prokaryotic) Phylogeny Webpage (March 2006). http://www.bacterialphylogeny.com/index.html