“Omnis cellula e cellula,” the idea that all cells come from cells, was first popularized by the German cell pathologist Rudolf Virchow in the middle of the nineteenth century. Each cell in organisms living today originated through countless sequential cell divisions, and is connected through an unbroken chain of cells to a primordial cell. How that cell developed is an interesting question!
The origination of eukaryotes from prokaryotic cell ancestors signified a large evolutionary leap. Present-day eukaryotic cells are significantly larger than prokaryotic cells (being 10–30 times larger in linear dimensions, and roughly 1000–10,000 times larger in volume, than a typical bacterium such as Escherichia coli). The genome sizes and total gene numbers of eukaryotes increased, allowing increased functional complexity. That extended to the architecture of the cell (development of internal membrane systems, organelles, and a highly-sophisticated cytoskeleton) and to information processing/gene regulation (the physical separation of transcription from translation, and the development of RNA splicing, RNA interference, and so on). The subsequent evolution of multicellularity allowed extraordinary functional complexity.
The first eukaryotic cell is thought to have originated about 1.5–2 billion years ago. It is now widely accepted to have occurred by a special type of cell fusion, endosymbiosis, in which one cell engulfs another cell without destroying it (so that functions of both cells are retained). Because each of the original cells had a genome and a protein- synthesizing capacity (ribosomes, transfer RNAs, and associated translation factors), the cell fusion resulted in a stable cell with two genomes and two sets of protein- synthesis machinery (Figure 1).
Fig1. Cell fusion by cell engulfment usually results in phagocytosis, but a rare alternative is co-operative symbiosis. Cell engulfment is a form of cell fusion in which one cell, the host cell, has the flexibility to send out cytoplasmic processes to surround another cell and internalize it. (A) The internalized cell is typically destroyed by the host cell (phagocytosis): the genome is cleaved into small fragments and other components are degraded. This process has intermittently allowed a form of horizontal gene transfer during evolution, notably between prokaryotic cells, whereby DNA fragments from the genome of the internalized cell are incorporated into the host-cell genome (see Figure 2A). (B) A rare alternative fate for the internalized cell is that it is not destroyed; instead it co-operates with the host cell in a symbiotic relationship known as endosymbiosis (the internalized cell is known as an endosymbiont). In this case, the fusion cell continues with two genomes and two sets of protein-synthesis machinery (including ribosomes and a complement of transfer RNAs), one of each donated by the host cell and one by the internalized cell. The eukaryote lineage arose by this process; see Figure 2C.
Endosymbiosis can explain the origin of the two eukaryotic organelles that have their own independent genomes and protein-synthesis capacity: mitochondria and chloroplasts. Mitochondria are found in all eukaryotic cells, and originated when an anaerobic eukaryotic precursor cell engulfed an aerobic cell (the endosymbiont became a proto mitochondrion). At that time, oxygen levels were known to be rising rapidly in the atmosphere, and engulfing an aerobic cell would have been advantageous for the anaerobic host cell. (Chloroplasts are thought to have evolved from secondary symbiosis in which a photosynthesizing cell was engulfed by an early eukaryotic cell, giving rise to a eukaryotic lineage leading to plants and algae.)
During the long period of evolutionary time that has elapsed since these endosymbiotic events, there has been an expansion in the size of the host-cell genome, giving rise to the nuclear genome of eukaryotic cells. At the same time, the mitochondrial and chloroplast genomes evolved through a process where most of the original DNA present in the endosymbiont was shed from the genome. The human mitochondrial genome, for example, is only 16.6 kb (about 0.3% of the size of an average prokaryotic genome).
Both archaeal and bacterial DNA sequences contributed to the evolution of eukaryotic genomes. That became clear when inferred eukaryotic protein sequences (much more evolutionarily conserved than the corresponding gene sequences) were compared against translated coding sequences from prokaryotes in order to identify significantly related sequences. Many eukaryotic genes do not have any recognizable equivalent (homolog) in prokaryotic genomes, but some eukaryotic genes have clear homologs in archaea, and some others have clear homologs in bacteria. The archaea– eukaryote homologs are especially common in information processing systems such as DNA replication, transcription, recombination, and DNA repair. By contrast, the bacteria eukaryote homologs are more likely to have operational functions, working in metabolic pathways, as membrane components, and so on.
Phylogenetic analyses of genes in current mitochondria clearly indicate that the endo symbiont that gave rise to the mitochondrial genome was an α-proteobacterium. The host cell was a complex type of archaeon (archaea, but not bacteria, have clear homologs of important eukaryotic proteins working in nuclear DNA replication, and also homologs of eukaryotic histones and of actins that work in the eukaryotic cytoskeleton). However, the nuclear genome of eukaryotes is a mosaic of DNA sequences that originated from both archaeal and bacterial genomes.
The hybrid origins of the nuclear genome are due to repeated rounds of horizontal gene transfer in which sequence components of the genome of various bacterial cells were integrated into the genome of the archaeal eukaryotic precursor cell and its descendants. First, the archaeal eukaryotic precursor cell is envisaged to have developed complexity by repeated phagocytosis of diverse bacterial cells: after degrading each engulfed bacterial cell and cleaving its DNA, bacterial DNA fragments integrated into the host cell’s genome, extending its size and ultimately its functional capabilities. Then, after the endosymbiosis that gave rise to the proto-mitochondrion, many DNA sequences were intermittently shed from the α-proteobacterial genome and transferred to the archaeal host-cell genome (Figure 2). That may have happened over a short period of evolutionary time, but even in modern times mtDNA sequences are occasionally transferred from the mitochondrial to the nuclear genome.
Fig2. A key step in eukaryote evolution was an endosymbiotic event in which a complex anaerobic archaeon engulfed an aerobic α-proteobacterium. The archaeon is imagined to have had some internal membrane structure (not shown here for clarity). (A) It may have achieved complexity through multiple previous events in which it phagocytosed bacterial cells, leading to destruction of the internalized cell and the release of short DNA sequences that were then incorporated into the archaeal genome. After several cycles of internalizing bacterial cells and horizontal gene transfer (HGT) from the ingested bacterial genomes, the host cell genome became a mix of archaeal (blue) and bacterial (orange) DNA sequences. (B) The resulting increase in genome complexity could have speeded-up evolution, leading to the development of additional internal membranes. (C) The key endosymbiosis event involved internalizing an α-proteobacterium. Thereafter, DNA sequences were periodically shed from the internalized cell's genome over a long period of evolutionary time: the genome became much smaller, giving rise to present day mitochondrial genomes. Some of the discarded α-proteobacterial sequences were degraded and lost, but others were incorporated into the archaeal genome (D), which subsequently became more complex, giving rise to the nuclear genome of eukaryotes. This model has been supported by the recent discovery of Lokiarchaeota, complex archaea whose genomes encode an expanded repertoire of eukaryotic signature proteins that suggest sophisticated membrane-remodeling capabilities (see Spang A et al. [2015] Nature 521:173–179; PMID 25945739). (Adapted from Martijn J & Ettema TJ [2013] Biochem Soc Trans 41:451–457; PMID 23356327. With permission from Biochemical Society.)
