T he idea that the eukaryotic cell is actually a colony of microbes was first suggested in the

The Serial Endosymbiosis Theory of Eukaryotic Evolution

by Jeremy Mohn

(c) 1998

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he transition between eukaryotes, cells with nuclei, and prokaryotes, cells which lack nuclei, is considered by many biologists to be the most profound change in evolutionary history. In an attempt to describe the way in which this gap was bridged, scientists have proposed the serial endosymbiosis theory (SET). The term "endosymbiosis" specifies the relationship between organisms which live one within another (symbiont within host) in a mutually beneficial relationship. The SET states that the evolution of eukaryotes from prokaryotes involved the symbiotic union of several previously independent ancestors. According to the theory, these ancestors included a host cell, an ancestor of mitochondria, an ancestor of chloroplasts, and, more controversially, a prokaryote that brought with it the structures that today provide cellular motion.

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he idea that the eukaryotic cell is actually a colony of microbes was first suggested in the 1920s by American biologist Ivan Wallin (Fausto-Sterling 1993). The originator of the modern version of the SET is biologist Lynn Margulis. In 1981, Margulis published the first edition of her book entitled Symbiosis in Cell Evolution in which she proposed that

eukaryotic cells originated as communities of interacting entities that joined together in a specific order. With time, the members of this union became the organelles of a single host (Margulis 1993). The organelle progenitors could have gained entry into a host cell as undigested prey or as an internal parasite after which the combination became mutually beneficial to both organisms. As the organisms became more interdependent, an obligatory symbiosis evolved.

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he SET postulates that the ancestors of mitochondria were free-living bacteria, similar to

today’s Daptobacter and Bdellovibrio, that developed the ability to efficiently respire oxygen

(Margulis and Sagan 1987). The ancestors of chloroplasts, today’s cyanobacteria, were

originally independent photosynthetic organisms. In addition, the whiplike cilia that are common in eukaryotes but are not found in prokaryotes are thought to have derived from still another group of free-living bacteria, the modern spirochetes. According to the SET, the

original prokaryotic host cell was an archaebacterium, similar to today’s Thermoplasma, that could withstand high temperatures and acidic conditions (Margulis and Sagan 1987). This host cell was neither photosynthetic nor capable of effectively using oxygen.

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hroughout her writings, Margulis contends that symbiosis is a major driving force behind evolution. In her opinion, cooperation, interaction, and mutual dependence among life forms

allowed for life’s eventual global dominance. As a result, Darwin’s notion of evolution as the

incomplete. According to Margulis and Sagan (1986), "Life did not take over the globe by combat, but by networking." Rather than focus solely on the elimination of competitors,

Margulis’ view of evolution downplays competition itself on the basis of symbiotic relationships.

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ne early and important discovery in support of the SET occurred in the laboratory of Kwang W. Jeon, a biologist at the University of Tennessee. Jeon witnessed the establishment of an amoeba-bacteria symbiosis in which new bacterial symbionts became integrated in the host amoeba (Jeon 1991). In 1966, when the bacteria first infected the amoebas, they were lethal to their hosts. However, as time progressed, some of the infected amoebas survived and became dependent on their newly acquired endosymbionts within a few years. Jeon was able to prove this dependency by performing nuclei transplants between infected amoebas and amoebas lacking the bacteria. If left alone, the hybrid amoebas died in a matter of days. Yet if he reinfected these hybrids with the once-lethal bacteria, the amoebas recovered and once again began to grow (Margulis and Sagan 1987). This discovery served to demonstrate that endosymbiosis could provide a major mechanism for cellular evolution and explain the introduction of new species (Jeon 1991).

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lthough some of Margulis’ ideas remain controversial, there is mounting evidence in

support of the SET (Fausto-Sterling 1993). The bulk of this evidence serves to defend the notion of an endosymbiotic origin of mitochondria and chloroplasts. The recognition that new mitochondria and chloroplasts can arise only from preexisting mitochondria and chloroplasts was one of the first clues. Scientists found that mitochondria and chloroplasts cannot be formed in a cell that lacks them because nuclear genes only code for some of the proteins of which they are made. Also, both mitochondria and chloroplasts have their own sets of genes that are more similar to those of prokaryotes than those of eukaryotes. They both contain a circular molecule of DNA, just like that found in prokaryotes. Finally, both mitochondria and chloroplasts have their own protein-synthesizing machinery. Their ribosomal structures and their ribosomal RNA (rRNA) more closely resemble those of prokaryotes. These three lines of evidence have been cited to firmly establish the theory of the origin of mitochondria and chloroplasts through the process of endosymbiosis.

that emphasizes the role of various kinds of mutations in the evolutionary separation of eukaryotic cells from prokaryotic cells.

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he main controversy between the endogenous and exogenous hypotheses for the origin of undulipodia rests upon a question of chronology. Proponents of the endogenous hypothesis claim that microtubules preceded the origin of undulipodia, which eventually arose

endogenously. In contrast, the exogenous hypothesis states that motility symbioses gave rise to cells with undulipodia, and this acquisition subsequently led to the internal structures involved in mitosis (Bermudes, Margulis, and Tzertzinis1987). Although the symbiotic origin of undulipodia is gaining support, the controversy is yet to be solved. According to Bermudes and Margulis (1985), there is insufficient evidence to prove either direct filiation or the symbiotic hypothesis for the origin of undulipodia.

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n important distinctive element of the SET is the overall chronology of symbiotic

acquisitions in the origin of the eukaryotic cell. In order to fully understand the theory’s

implications for the classification of all life forms, a brief summary of the current interpretation of endosymbiotic events is necessary. According to the theory, eukaryotes evolved when archaeal and eubacterial cells merged in anaerobic symbiosis. The archaeal cell provided the cytoplasm while the eubacterial cell (a spirochete) allowed for mobility and, eventually, mitosis. Some of these anaerobic cells then incorporated oxygen-respiring eubacteria (similar to Daptobacter or Bdellovibrio) to become mitochondria-containing aerobes from which most protoctists, animals, and fungi evolved. Finally, some of these aerobes went on to incorporate photosynthesizing cyanobacteria to become chloroplast-containing algae and plants. The divisions or domains implied by this description (Archaea, (true)Bacteria, and Eukarya) are consistent with the widely acknowledged classification system described by Olsen, Woese, and Overbeek (1994).

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lthough the nucleus is the defining characteristic of the eukaryotic cell, the origin of this organelle and its relation to symbiosis is uncertain. Margulis tends to favor a process

involving the combination of direct filiation and symbiosis as the source of the nucleated cell. She believes that some prokaryotic cells evolved primitive nuclei through direct filiation but remained prokaryotic. Others evolved these same structures but also acquired other symbiotic genes and consequently became eukaryotes (Margulis 1993). Overall, the traditional view of the origin of the nucleus states that the nuclear genome originated through direct evolution from an archaebacterial ancestor.

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1996 paper by Golding and Gupta disputes the traditional view of the origin of the nucleus and suggests an alternative called the chimeric model. The term "chimeric" refers to an organism containing tissues from at least two genetically distinct parents. The chimeric model proposes that the first eukaryotic cell arose as the result of a unusual fusion event between a Gram-negative eubacterium (host) without a cell wall and an archaebacterium (symbiont) in which both parents made major contributions to the cell’s nuclear genome. The

nucleus appeared as the result of the folding in of the host’s membrane around the engulfed

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he chimeric model is based on genetic and biochemical evidence. One piece of genetic evidence that supports the model is the fact that prokaryotic cells are homogenomic (having genetic material from one parent only), whereas eukaryotic cells are heterogenomic (having genetic material from more than one parent). Biochemical evidence in support of the chimeric model involved the phylogenetic, or evolutionary, analysis of sequence data from proteins. This analysis demonstrated a close relationship between Gram-negative bacteria and

eukaryotes on one hand and Gram-positive bacteria and archaebacteria on the other (Golding and Gupta 1996). Even more protein sequence data suggested a relationship between

eukaryotes and archaebacteria. These data imply that a symbiotic relationship between Gram-negative bacteria and archaebacteria as the progenitors of the eukaryotic cell is feasible. Overall, the sequence data support the chimeric model.

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ecent research by Martin and Müller (1998) into the origin of the mitochondrion has led to a new theory of endosymbiosis called the "hydrogen hypothesis." In the current picture of the origin of the eukaryotic cell, the mitochondrion was a "lucky accident" (Vogel 1998). The ancestral host cell simply engulfed the mitochondrion ancestor, did not fully ingest it, and an even more successful cell resulted. According to the hydrogen hypothesis, however, the first eukaryotic cell did not form simply by accident. Instead, it was the result of a purposeful union between an archaebacterial host cell, a methanogen that consumed hydrogen and carbon dioxide to produce methane, and a future mitochondrion symbiont that made

hydrogen and carbon dioxide as waste products of anaerobic metabolism. Thus, although the symbiont was probably capable of aerobic respiration, the symbiosis began as a result of the

products of anaerobic metabolism. The host’s dependence upon hydrogen produced by the

symbiont is identified as the selective principle that consolidated the common ancestor of eukaryotic cells (Martin and Müller 1998).

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he hydrogen hypothesis has some important implications that contradict the current view of the relationship between eukaryotes and archaebacteria. In the current view, the eukaryotes branched off from the archaebacteria long before the archaebacteria had divided into their present-day groups. The hydrogen hypothesis implies that the first eukaryotes appeared much later in the evolutionary picture, meaning they are more closely tied to the archaebacteria. In order for the hydrogen hypothesis to be confirmed, an analysis of the complete sequences of eukaryotic and archaebacterial genomes must be completed (Vogel 1998).

nucleic acid metabolism while the latter provided most metabolic characteristics (López-Garcia and Moreira 1998). Mitochondria are thought to have derived from a later,

independent symbiotic event. As with the hydrogen hypothesis, further genetic sequencing analyses are necessary in order for the claims of the syntrophic hypothesis to be upheld.

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t has been nearly thirty years since Lynn Margulis first published a book on the origin of eukaryotic cells. Since that time, biology has undergone extraordinary changes. The most noticeable change is the extensive accumulation of sequence data for both nucleic acids and proteins. The collection of new data will undoubtedly lead to continuous revision of the serial endosymbiosis theory of the origin of the eukaryotic cell. Despite the uncertain future, the crucial foundation has been laid. Symbiosis is now accepted by the scientific community as an important factor in generating evolutionary change. The next steps include the

development of more elaborate methods to interpret genetic and molecular sequence data and the undertaking of a fresh look at the fossil record. These tactics might reveal significant information concerning one of the most challenging and fascinating problems in evolutionary biology, the origin of the eukaryotes.

Bibliography

Bermudes, D., L. Margulis, and G. Tzertzinis. 1987. Prokaryotic Origin of Undulipodia. In: Endocytobiology III (eds. John J. Lee and Jerome F. Fredrick). The New York Academy of Sciences, New York, pp. 187-197.

Bermudes, D., and L. Margulis. 1985. Symbiosis as a Mechanism of Evolution: Status of the Symbiosis Theory. Symbiosis 1: 101-124.

Fausto-Sterling, A. 1993. Is Nature Really Red in Tooth and Claw? Discover 14: 24-27.

Jeon, K.W. 1991. Amoeba and x-Bacteria: Symbiont Acquisition and Possible Species Change. In: Symbiosis as a Source of Evolutionary Innovation (eds. L. Margulis and R. Fester). The MIT Press, Cambridge, Mass., pp. 118-131.

López-García, P., and D. Moreira. 1998. Symbiosis Between Methanogenic Archaea and delta-Proteobacteria as the Origin of Eukaryotes: The Syntrophic Hypothesis. Journal of Molecular Evolution 47: 517-530.

Margulis, L. 1981. Symbiosis in Cell Evolution, 1st Edition. Freeman, New York.

Margulis, L. 1993. Symbiosis in Cell Evolution, 2nd Edition. Freeman, New York.

Margulis, L., and D. Sagan. 1986. Microcosmos. Summit Books, New York.

Margulis, L., and D. Sagan. 1987. Bacterial Bedfellows. Natural History 96(3): 26-33.

Olsen, G.J., C.R. Woese, and R. Overbeek. 1994. The Winds of (Evolutionary) Change: Breathing Life into Microbiology. Journal of Bacteriology 176(1): 1-6.