Symbiosis As a General Principle in Eukaryotic Evolution

Home , Trophosome

Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis as a General Principle in Eukaryotic Evolution

Angela E. Douglas

Department of Entomology, Cornell University, Ithaca, New York 14853 Correspondence: [email protected]

Eukaryotes have evolved and diversified in the context of persistent colonization by nonpathogenic microorganisms. Various resident microorganisms provide a metabolic capability absent from the host, resulting in increased ecological amplitude and often evolutionary diversification of the host. Some microorganisms confer primary metabolic pathways, such as photosynthesis and cellulose degradation, and others expand the repertoire of secondary metabolism, including the synthesis of toxins that confer protection against natural enemies. A further route by which microorganisms affect host fitness arises from their modulation of the eukaryotic-signaling networks that regulate growth, development, behavior, and other functions. These effects are not necessarily based on interactions beneficial to the host, but can be a consequence of either eukaryotic utilization of microbial products as cues or host– microbial conflict. By these routes, eukaryote–microbial interactions play an integral role in the function and evolutionary diversification of eukaryotes.

ukaryotes do not live alone. They bear living The current interest in the microbiota as- Ecells of bacteria (Eubacteria and Archaea), sociated with eukaryotes stems from key tech- and often eukaryotic microorganisms, on their nological advances for culture-independent surfaces and internally without any apparent analysis of microbial communities, especially ill effect. Furthermore, there is now persuasive high-throughput sequencing methods to iden- evidence that all extant eukaryotes are derived tify and quantify microorganisms (Caporaso from an association with intracellular bacteria et al. 2011; Zaneveld et al. 2011). The Human within the Rickettsiales that evolved into mi- Microbiome Project (commonfund.nih.gov), tochondria (Williams et al. 2007), with the MetaHIT (metahit.eu), and other initiatives implication that this propensity to form persis- are yielding unprecedented information on the tent associations has very ancient evolutionary taxonomic diversity and functional capabilities roots. In this respect, the eukaryotes are differ- of microorganisms associated with humans, ent from the bacteria, among which only a sub- other animals, and also plants, fungi, and uni- set associate with eukaryotes, speciﬁcally mem- cellular eukaryotes (the protists), as well as abi- bers of about 11 of an estimated 52 phyla of otic habitats (Qin et al. 2010; Muegge et al. 2011; Eubacteria (Sachs et al. 2011) and a tiny minor- Human Microbiome Project 2012a; Lundberg ity of Archaea (Gill and Brinkman 2011). et al. 2012; Bourne et al. 2013). Much of this

Editors: Patrick J. Keeling and Eugene V. Koonin Additional Perspectives on The Origin and Evolution of Eukaryotes available at www.cshperspectives.org Copyright # 2014 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a016113 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113

1 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

research has focused on the Eubacteria, but eu- This article comprises three sections: the karyotic members of the microbiota, especially two types of interaction are considered in turn, the fungi, are increasingly being investigated with the key patterns and processes illustrated (Iliev et al. 2012; Findley et al. 2013). by specific examples from a range of symbioses Although driven by technological change, in animals, plants, and other eukaryotes; and these culture-independent studies of the micro- the concluding comments address some key biota of humans and other eukaryotes are hav- unanswered questions about symbiosis in eu- ing profound consequences for our conceptual karyotes. This article does not review the full understanding. In particular, there is a growing diversity of associations made in this article on appreciation that the germ theory of disease, the general principles of symbiosis in eukary- which has played a crucial role in improving otic evolution; interested readers are referred public health and food production through to Douglas (2010). the 20th century, has also led to the widespread but erroneous belief that all microorganisms associated with animals and plants are patho- SYMBIOSIS AS A SOURCE OF NOVEL gens. This outmoded perception is increasingly CAPABILITIES being replaced by the recognition that eukary- The Ancient Evolutionary Roots of Symbioses otes are chronically infected with benign and Founded on Metabolism beneficial microorganisms, and that disease can result from disturbance to the composition Eukaryotes have repeatedly gained access to or activities of the microbiota (McFall-Ngai complex metabolic capabilities by forming sym- et al. 2013; Stecher et al. 2013). bioses with other organisms that possess these This article reviews the pervasive impact of functions. By acquiring the organism (not just symbiosis with microorganisms on the traits the genes), eukaryotes have gained not only the of their eukaryotic hosts and the resultant con- genes coding specific enzymes, but also the ge- sequences for the evolutionary history of eu- netic and cellular machinery for their regulated karyotes. For the great majority of associations, expression. the effects of symbiosis can be attributed to The capacity to acquire metabolic capabili- two types of interaction. The first interac- ties by symbiosis is evident in the common an- tion—“symbiosis as a source of novel capabili- cestor of all extant eukaryotes and can be linked ties”—is founded on metabolic or other traits to the metabolic limitations in the lineage giv- possessed by the microbial partner but not the ing rise to the eukaryotes. In particular, this eukaryotic host. By gaining access to these ca- lineage lacked the capacity for autotrophic pabilities, eukaryotes have repeatedly derived carbon fixation and aerobic respiration; these enhanced nutrition, defense against natural en- traits had evolved in the Eubacteria, presumably emies, or other selectively important character- more recently than the common ancestor of istics. The second interaction—“the symbiotic the two groups. The association with the a-pro- basis of health”—comprises the improved vigor teobacterial ancestor of mitochondria probably and fitness that eukaryote hosts gain through evolved 1–2 billion years ago. All extant eukary- microbial modulation of multiple traits, includ- otes have mitochondria or are descended from ing growth rates, immune function, nutrient mitochondriate ancestors, raising the possibili- allocation, and behavior, even though the effects ty that the acquisition of mitochondria defined cannot be ascribed to specific microbial capa- the evolutionary origin of eukaryotes (Embley bilities absent from the host. There is increasing and Martin 2006). (We cannot, however, ex- evidence that the health benefits of symbiosis clude the alternative scenario that the ancestor are commonlya consequence of microbial mod- of mitochondria was acquired by bona fide eu- ulation of the signaling networks by which the karyotic cells, with the subsequent extinction of growth and physiological function of eukaryote all amitochondriate eukaryotic lineages.) Fur- hosts are coordinated. thermore, the mitochondria have undergone

2 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

substantial evolutionary diversification, includ- size with a high surface area:volume ratio, al- ing the transformation into hydrogenosomes, though some bacteria can attain relatively large functionally distinct organelles that generate cell sizes through various adaptations (Schulz ATP with the production of hydrogen and lack and Jorgensen 2001). Furthermore, the bac- oxidative phosphorylation (Hjort et al. 2010). terial-derived organelles represent additional Hydrogenosomes have evolved multiple times subcellular compartments with key roles in me- in secondarily anaerobic eukaryotes, including tabolism (e.g., b-oxidation of fatty acids, steroid various ciliate protists and the lorificeran ani- hormone synthesis) and signaling (e.g., apopto- mals in anoxic marine sediments (van der Gie- sis, calcium signaling), thereby enhancing cellu- zen et al. 2005; Danovaro et al. 2010). The evo- lar efficiency and capacity to mediate complex lutionary history of eukaryotic acquisition of interactions. oxygenic photosynthesis by symbiosis with the cyanobacterial ancestor of chloroplasts is also Symbioses Founded on Primary Metabolism complex. Unlike mitochondria, which evolved of Microbial Symbionts just once, chloroplasts have evolved from two different cyanobacterial groups (Keeling 2013). Symbiosis with microorganisms is not restricted One cyanobacterial-derived chloroplast is allied to associations involving eubacterial endosym- to Synechoccus and has been reported in the rhi- bionts that evolved in the distant ancestors of zarian amoeba Paulinella chromatophora (Na- modern eukaryotes. Rather, the capacity to ac- kayama and Ishida 2009; Nowack and Grossman quire bacterial or eukaryotic microorganisms is 2012). The other lineage is in the very successful a persistent theme in the biology of the eukary- Archaeplastids, including both algae (e.g., Rho- otes and a major factor shaping adaptation of dophytes, Chlorophytes) and terrestrial plants, eukaryotes to different habitats and lifestyles, as with the subsequent evolution of some algae well as the evolutionary diversification of many into secondary, and even tertiary, chloroplasts groups. Particularly striking examples are pro- in further groups of eukaryotes (Keeling 2013). vided by the acquisition of photosynthetic algae Without doubt, the evolutionary and eco- (eukaryotic microorganisms that are, them- logical success of the eukaryotes is founded on selves, the product of symbiosis) by fungi, gen- their acquisition of aerobic respiration and pho- erating the lichens that account for nearly half of tosynthesis by symbiosis, with the transition of all Ascomycete fungal species, and by various bacterial symbionts to organelles. Without these animals, including the corals, whose capacity capabilities, the eukaryotes as a group would to form reefs in the photic zone is symbiosis have been excluded from oxic habitats (occu- dependent. pied by the photosynthetic cyanobacteria and Furthermore, aerobic respiration and pho- aerobic bacteria) and restricted to the low-ener- tosynthesis are not the only complex metabolic gy lifestyle dictated by hypoxia and anoxia. The traits acquired by eukaryotes through symbio- localization of electron transport chain in aero- sis, although none of the microbial partners bic respiration and photosynthesis to the intra- contributing these other traits are known to cellular compartments of mitochondria and have evolved into organelles. Nitrogen fixation plastids, respectively, provided additional evo- and chemosynthesis are two metabolic capa- lutionary opportunities for eukaryotes. The re- bilities that are apparently absent from the an- striction of energy production to the organellar cestral eukaryote and have been acquired by membranes, separate from cell membrane func- multiple eukaryotic groups by symbiosis. An- tion, permitted large cell size and associated re- giosperm plants of the eurosid clade are partic- duction in the ratio of (cell membrane surface ularly predisposed to associate with nitrogen- area)/(cell volume) without prejudicing energy fixing bacteria, notably the rhizobia (including production (Lane and Martin 2010). (Bacterial Rhizobium and Bradyrhizobium in the a-pro- cells with the respiratory chain localized to the teobacteria) and the actinobacteria Frankia. cell membrane are generally restricted to small The access to atmospheric nitrogen in these

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 3 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

plants facilitates their utilization of nitrogen- flagellates (the most basal animals, and closest poor soils, for example, in early succession com- relative of animals, respectively) feed on living munities, and is recognized as a contributory organisms, especially bacteria, which provide a factor to the evolutionary diversification of le- nutritionally balanced diet. gumes, with their large, nitrogen-rich seeds Repeatedly in the evolution of animals, sym- protected by nitrogen-containing toxins, in- biosis with microorganisms has enabled ani- cluding alkaloids (Houlton et al. 2008; Corby mals to escape from the nutritional constraint et al. 2011). Nitrogen-fixing symbioses have also of feeding on a nutritionally balanced diet. been reported in protists, for example, in ma- Many microbial symbionts of animals have rine diatoms (Foster et al. 2011), and some an- probably evolved by the progressive delay in animals, notably the wood-feeding shipworms imal digestion of food-associated microorgan- and some termites (Lechene et al. 2007; Desai isms, raising the evolutionary scenario of a shift and Brune 2012). in the animal to a poor-nutrient diet coupled to Chemosynthesis (the capacity to fix carbon the transition of nutrient acquisition by diges- dioxide using the energy derived from the oxi- tion to biotrophic release from intact microbial dation of reduced substrates, such as hydrogen, cells. Two diets for which animals require nu- hydrogen sulfide, and methane) is widely ex- tritional support from microbial symbionts ploited by animals. The habitats where these are vertebrate blood and plant sap, as indicated associations flourish are zones of oxic/anoxic by the possession of microbial symbionts by mixing, including aquatic sediments, hydro- all animals feeding on these diets through the thermal vents, and hydrocarbon seeps. Many life cycle (Buchner 1965). For example, symbi- animals in these habitats bear chemosynthetic otic microorganisms are borne in the gut or symbionts on their body surface (e.g., annelid specialized cells of the obligately blood-feeding worms), in gills (e.g., bivalve mollusks), or in a leeches, ticks, lice, and bedbugs, and they are central tissue called the trophosome (in pogo- believed to provide their animal hosts with B nophoran worms), and many display reduced vitamins. Plant sap feeding has also evolved capacity for feeding and a digestive tract that is multiple times, but only among insects of the much reduced or absent (Petersen et al. 2011; order Hemiptera (including whiteflies, aphids, Roeselers and Newton 2012). cicadas, and planthoppers). These insects derive Various eukaryotes have compounded the essential amino acids, nutrients in short supply metabolic limitations of their eukaryotic inher- in the plant phloem and xylem sap, and pos- itance by the loss of further metabolic capabil- sibly vitamins from their microbial partners ities. Reduction of metabolic scope is particu- (Douglas 2009). larly evident in the animals, which, as a group, Microbial symbioses have also played an im- lack the capacity to synthesize at least nine of the portant role in animal utilization of structural 20 protein amino acids (the essential amino ac- plant material, including lignocellulose. Her- ids) and various cofactors required for the func- bivory has evolved multiple times in the verte- tion of enzymes central to metabolism (e.g., brates and, where investigated, the extraction of various vitamins). The arthropods have, addi- energy from the ingested cellulose is dependent tionally, lost the capacity for sterol synthesis. on cellulolysis by symbiotic bacteria in an an- Generally, these lost metabolic capabilities com- aerobic portion of the gut, known as the fer- prise many reactions and tend to be energetical- mentation chamber. The waste products of the ly demanding (Wagner 2005). Organisms with bacterial fermentation are short-chain fatty ac- an ample dietary supply of amino acids or co- ids, such as acetic acid and butyric acid. These factors would gain no advantage from retaining products are transported into the epithelial cells these capabilities (relaxed selection) and argu- of the animal and via the blood to other organs, ably the selective advantage of energetic effi- where they are used as a substrate for aerobic ciency from losing them. As predicted from respiration (Karasov and Douglas 2013). Micro- these considerations, the sponges and choano- bial degradation of ingested lignocellulose and

4 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

fermentation of cellulose are generally less im- microbial partner, and perfect correlation be- portant for invertebrate, especially insect, her- tween expression of the secondary metabolic bivores, but can make an important contribu- capability in the host and presence of the mi- tion to the carbon economy of insects, such as crobial partner with these genes. This can be termites, wood roaches, wood wasps, and some illustrated by the contribution of bacterial sym- beetles, that feed on wood products of very low bionts to the production of a biologically active nutritional content (Geib et al. 2008; Suen et al. class of secondary compounds, the polyketides. 2010; Adams et al. 2011). Multiple factors may For example, the beetle Paederus bears bacte- contribute to the greater contribution of mi- ria of the genus Pseudomonas, which have the crobial symbionts to vertebrates than insects genes for polyketide synthase and linked re- feeding on structural plant material. They in- actions required for the production of the poly- clude the greater anatomical barriers to a fer- ketide profile of these animals (Piel et al. 2004a), mentation chamber in a small, highly aerobic and elimination of the Pseudomonas in Paederus insect than in a larger vertebrate with a predom- results in loss of polyketide production (Kell- inantly anoxic gut lumen, and the widespread ner 2001). Similarly, many grasses are protected occurrence of intrinsic cellulases (i.e., of ani- from herbivory by alkaloids that are synthe- mal origin) in invertebrates, including many in- sized by clavicipitaceous fungal endophytes sects, but apparently in no vertebrates (Davison that ramify through the plant tissues (Fletcher and Blaxter 2005; Calderon-Cortes et al. 2012). and Harvey 1981), and the genetic basis of the Consequently, microbial symbiosis is a general fungal synthesis of one key alkaloid loline by the principle for the evolution of herbivory in ver- fungal endophyte in the grass Lolium has been tebrates, but its significance for invertebrate an- established (Spiering et al. 2005). Secondary imals has to be assessed on a case-by-case basis. metabolites synthesized by microbial symbionts have also been shown to contribute to the protection against predators and pathogens in mul- Symbioses and Secondary Metabolism tiple benthic marine animals, including spong- Symbiotic microorganisms can also contribute es (Piel et al. 2004b), bryozoans (Sharp et al. to the secondary metabolism of their eukary- 2007), and tunicates (Kwan et al. 2012). otic hosts. “Secondary metabolism” refers to Just as secondary chemistry is very diverse, metabolic reactions and pathways that do not so are the routes by which eukaryotes have contribute directly to organismal growth and gained access to these often-complex biosyn- reproduction but that can be crucial to the fit- thetic pathways for secondary metabolite syn- ness of the organism in the natural environ- thesis. This is illustrated by recent research on ment. Secondary metabolism includes the syn- the source of carotenoid pigments in animals. thesis of toxins, antibiotics, pheromones and Carotenoids have antioxidant properties and allomones, and pigments, as well as the degra- are also used as pigments. Animals, generally, dation of toxins and other secondary metabo- are unable to synthesize carotenoids, and many lites. The capacity of eukaryotes for secondary derive carotenoids from their diet. However, the metabolism varies widely, even among closely carotenoid profile of some insects is indepen- related species, and the technical difficulties in dent of a dietary supply. In one group of in- working with secondary metabolism has led to sects, the whiteflies, the carotenoids are of sym- various failures to recognize the role of micro- biotic origin, with the carotenoid biosynthesis organisms in the secondary chemistry of genes coded by its bacterial symbiont Portiera some eukaryotes, as well as some unsubstanti- (Sloan and Moran 2013). In two other groups, ated claims of symbiotic secondary metabolism. the aphids and spider mites, the carotenoid Two complementary approaches provide an biosynthesis genes are encoded in the animal excellent test for the role of microbial symbionts genome, following independent lateral transfers in secondary metabolism: identification of the from fungi (Moran and Jarvik 2010; Altincicek relevant genes in the sequenced genome of the et al. 2012; Novakova and Moran 2012).

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 5 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

There is one further aspect to secondary fungus genome has multiple genes for laccases metabolism that deserves careful consideration: (a type of phenoloxidase). Enzymatically ac- the contribution of resident microorganisms tive laccase enzyme is passed through the gut to the detoxification of secondary metabolites. of ants feeding on the fungus and released This is currently a “hot topic” in biomedical onto plant material, where it can degrade plant research, in the light of evidence that the activ- compounds, such as tannins and flavonoids (De ities of the gut microbiota can determine the Fine Licht et al. 2013). half-life and metabolic fate of orally adminis- tered drugs, with clinically important impli- THE SYMBIOTIC BASIS OF HEALTH cations for drug efficacy and toxicity (Haiser and Turnbaugh 2012; Holmes et al. 2012; Haiser The function of all living organisms is orches- et al. 2013). An analogous issue has been of trated by signaling networks that coordinate persistent concern in the discipline of herbi- processes within individual cells and, for mul- vory for decades. Although herbivorous ani- ticellular forms, also among cells, tissues, or- mals generally possess a diverse array of detox- gans, and so on. It has long been known that ifying enzymes, including cytochrome P450 these regulatory networks can be manipulated monooxygenases, glutathione S-transferases, by pathogens and parasites, with various con- and esterases (Despres et al. 2007), symbiotic sequences ranging from the reorganization of microorganisms have long been invoked to me- the cytoskeleton and intracellular trafficking diate the detoxification of plant allelochemicals to the restructuring of host growth patterns, re- (Jones 1984; Berenbaum 1988; Dillon and Dil- productive schedules, and behavior (Gandon lon 2004). Supportive evidence comes from a et al. 2002; Bhavsar et al. 2007; Hughes et al. few systems. The microbiota in the foregut fer- 2012). It is now becoming increasingly clear mentation chamber (the rumen) of ruminant that the nonpathogenic resident microorgan- mammals has the potential to detoxify ingested isms can also modulate the signaling networks allelochemicals in the food, as illustrated by the of their eukaryotic hosts and that these manip- reported capacity of the rumen microbiota of ulations are generally advantageous for the host. indigenous Indonesian cattle to degrade the Although the data are still fragmentary, various toxic amino acid mimosine in the tropical le- lines of evidence are consistent with the hy- gume Leucaena leucocephala (Cheeke 1994). pothesis that eukaryotes derive health benefits Similarly, the capacity of reindeer to use rein- from symbiosis because their regulatory net- deer moss (a lichen, Cladonia rangiferina) has works are structured to function in the context been attributed to a bacterium Eubacterium of interactions with the resident microbiota. rangiferina in the reindeer rumen, which can The health benefits of symbiosis can be metabolize usnic acid, an abundant metabolite illustrated by plant-growth-promoting rhizo- in the lichen that is toxic to most animals bacteria (PGPRs), including strains of Azo- (Sundset et al. 2008, 2010). Plant allelochemical spirillum, Bacillus subtilis, Pseudomonas putida, detoxification has also been implicated in cer- and Enterobacter cloacae. As the term suggests, tain insect symbioses, notably bark-feeding bee- PGPRs are associated with plant roots and pro- tles and leaf-cutting ants. The gut microbiota of mote plant growth. The underlying processes the mountain pine beetle Dendroctonus ponder- are complex and variable, but very commonly osae include bacteria of the genera Pseudomo- involve the capacity to synthesize signaling mol- nas, Serratia, Rahnella, and Burkholderia that ecules, including plant hormones, for example, bear genes involved in the degradation of ter- the auxin indole-3-acetic acid (IAA), and vola- penes, the principal defensive compounds of tiles, for example, 2,3-butanediol (Spaepen the trees infested by these beetles (Adams et al. et al. 2007; Lugtenberg and Kamilova 2009; 2013). The leaf-cutting ant Acromyrmex echina- Roca et al. 2013). The best-studied interaction tior maintains, and feeds on, the symbiotic fun- relates to PGPR-derived IAA, which triggers gus Leucocoprinus gongylophorus in its nest. The increased root branching and a higher densi-

6 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

ty of root hairs. This altered root morphology promote host health and vigor by increasing the enhances nutrient uptake from the soil, there- amplitude of host signaling. by promoting plant growth (Dobbelaere et al. The hyperlipidemia and hyperglycemia 1999; Steenhoudt and Vanderleyden 2000). The displayed by Drosophila containing mutant A. important implication of these results is that pomorum are reminiscent of the elevated lip- the plant regulatory networks controlling the id and glucose levels in the laboratory mouse pattern of plant growth are not structured to treated with antibiotics that alter the composi- generate optimal growth of microbe-free plants, tion of the gut microbiota (Cho et al. 2012). The which is achieved only in the context of signal gut microbiota of the mouse can also be altered exchange with associated rhizosphere bacteria. by diet or mutation, especially of the mouse The IAA-producing PGPRs are an example immune system and nutrient signaling, with of resident microorganisms that influence host correlated phenotypic lesions, especially in nu- growth by the release of molecules that are also trient allocation and immune function (Mas- an integral part of the host-signaling network lowski and Mackay 2011; Claesson et al. 2012; (in this case, a plant hormone). Other com- Maynard et al. 2012). Transplant studies sug- pounds produced by microbial symbionts are gest that the altered microbial community like- not known elements of the host-signaling net- ly contributes to the altered host phenotype. work but, nevertheless, act to modulate (ampli- When introduced to germ-free control mice fy or dampen) host signaling. One example (reared on the standard diet/of wild-type geno- comes from research on the association between type), the recipients display similar deleterious the Drosophila fruit fly and its gut microbiota. phenotypic traits (Vijay-Kumar et al. 2010; When the microorganisms are eliminated, the Smith et al. 2013). These various data sets re- Drosophila display depressed development rates inforce the growing appreciation that the com- and elevated levels of lipid and circulating glu- position and activities of the resident micro- cose, similar to the phenotypic traits of flies biota are important for host health, such that with impaired insulin signaling (Shin et al. perturbation of the microbiota can contribute 2011). Flies infected with a mutant of a domi- to chronic ill health, a condition known as “dys- nant bacterial symbiont, Acetobacter pomorum, biosis.” The concept of dysbiosis, first coined a that cannot produce the enzyme pyrroloquino- century ago (Metchnikoff 1910), has gained rel- line quinone-dependent alcohol dehydrogenase evance in the context of hypotheses put forward (PQQ-ADH) also display these traits, together to account for the increase in immunological with reduced expression of the genes for insu- and metabolic disease in humans, with reduced lin-like peptides (dilp-3 and dilp-5). PQQ-ADH exposure of children to environmental micro- mediates the oxidation of ethanol to acetic acid. organisms (hygiene hypothesis) or to specific When acetic acid was supplied in the food, de- members of the human resident microbiota velopment rates, lipid and glucose contents, and (disappearing microbiota hypothesis) as pos- dilp gene expression in flies bearing the mutant sible drivers (Strachan 1989; Blaser and Falkow bacteria shifted to values found in conventional 2009). flies. These data suggest that acetic acid pro- Given the fitness costs of dysbiosis, the sus- duced by wild-type A. pomorum stimulates in- ceptibility of the regulatory circuits of animals sulin signaling in the fly. Although the processes and plants to modulation by their resident mi- by which acetic acid interacts with insulin sig- crobiota appears as a very real vulnerability. naling are unknown, the resultant speeding of How is it that eukaryote-signaling networks larval development is advantageous for the in- are not insulated from the influence of resident sect, which develops in rotting fruit and must microorganisms, but appear to be under joint complete larval development before the fruit host–microbial control? resources are exhausted. As with the IAA-pro- Two sets of processes may contribute to the ducing PGPRs associated with plant roots, the symbiotic basis of health. The first is that micro- acetic-acid-producing bacteria in fruit fly guts organisms provide a reliable cue for current or

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 7 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

future environmental conditions. Eukaryotes the immune system and other defenses can that respond appropriately to the microbial proliferate, and it is also frequently a route for products, that is, display regulated changes in dispersal. Consequently, many microorganisms growth or developmental patterns, behavior, have no selective interest in the reproductive and the like, would be at a selective advantage. output of their host. (Exceptionally, the various For example, the profile of metabolic end-prod- maternally inherited forms are in conflict with ucts from bacteria associated with rotting fruit the host over host sex ratio.) Thus, microorgan- may provide a reliable cue for the longevity of isms in the animal gut may favor hyperphagia the fruit resource, enabling Drosophila larvae to despite its negative consequences for host fit- titrate their developmental time to environmen- ness, modulate gut peristalsis rates to optimize tal circumstance. Specifically, the amplified in- their residence time at the expense of optimal sulin production in response to Acetobacter-de- nutrient absorption by the host, and dampen rived acetic acid increases developmental rates, immune responses to favor their persistence and this may be highly adaptive in the natural (de La Serre et al. 2010; Round et al. 2011; Mat- environment. Microbial products are used as sumoto et al. 2012; Maynard et al. 2012). cues by various eukaryotes. For example, a sul- Counterintuitively, host–microbial conflict fonolipid released from specific bacteria, Algo- over the amplitude of host-signaling pathways riphagus machipongonensis, induces colony for- can lead to host dependence, but only where the mation in choanoflagellates (Alegado et al. prevalence of the interacting microorganisms 2012); N-acyl homoserine-lactones (quorum- in the host population is very high. This impor- sensing molecules) released from Vibrio bacteria tant effect was first shown by research on the promote settling of motile zoospores of the relationship between a parasitic wasp, Asobara green alga Enteromorpha (Joint et al. 2002); tabida, and the vertically transmitted bacterium and compounds released from the bacterium Wolbachia. Several lines of evidence suggest Pseudoalteromonas associated with the substrate that Wolbachia induces oxidative stress and a in marine environments promote the settling linked dampening of apoptotic signaling, prob- and metamorphosis of barnacle larvae (Had- ably as a result of disruption of iron metabo- field 2011). lism (Kremer et al. 2009). As a likely conse- I describe these various compounds as cues quence, elimination of Wolbachia by antibiotic because their production by microorganisms is treatment results in massive apoptosis (pro- independent of the response of the eukaryotic grammed cell death) of the ovaries, leaving the host, that is, whether and how a eukaryote de- wasp reproductively sterile. It has been argued rives information from microbial compounds that, over evolutionary time, the wasp apoptotic has no effect on their production by the micro- pathways have gained heightened responsive- organisms. If a microbe-derived compound is a ness, in compensation for the inhibitory manip- reliable cue, the signaling network of the eu- ulation by Wolbachia (Pannebakker et al. 2007). karyote may evolve to increasing dependence Importantly, this effect is constitutive (presum- on that cue through reduced responsiveness to ably because Wolbachia is always present under other environmental factors, and this may result natural conditions), with the consequence that in dependence on specific microbial products appropriate apoptotic signaling requires the for sustained function of the signaling network manipulative intervention of the Wolbachia bac- and, ultimately, host health. teria. Analogous host compensation for micro- The alternative basis for microbial impacts bial manipulation may contribute to the mul- on host-signaling networks derives from con- tiple demonstrations of interactions between flict between the microorganisms and host. the resident microbiota and the developmental, Conflict is inevitable because of incomplete se- nutritional, neurological, and immunological lective overlap between a eukaryotic host and its health of animals (Stappenbeck et al. 2002; resident microbiota. A eukaryote is a nutrient- Smith et al. 2007; Bravo et al. 2011; Olszak rich patch in which microorganisms tolerant of et al. 2012). Additionally, host dependence on

8 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

microbial products for sustained health may be cent advances in single-cell imaging and sin- retained in eukaryotic lineages, where the con- gle-cell sequencing (Pamp et al. 2012; Pernice flict is resolved because of the sheer complexity et al. 2012; Lasken 2013) offer unprecedented of signaling networks. Elimination of microbial opportunities to investigate such heterogeneity. modulation of one pathway may be selected These ecological issues segue into long- against because the multiple, knock-on effects standing evolutionary questions, particularly on linked signaling pathways are highly delete- whether the microbiota can influence the spe- rious. Ultimately, the symbiotic basis of host ciation patterns and evolutionary diversifica- health may only be explicable in the context of tion of their hosts (Brucker and Bordenstein the deep evolutionary history of interactions 2013). In certain instances, evolutionary change between eukaryotes and their resident micro- may be facilitated by among-microbe transfer of biota. symbiosis-related gene clusters via “symbiosis islands” (Finan 2002), equivalent to pathoge- nicity islands in pathogenic bacteria, or by the CONCLUDING COMMENTS displacement of one microbial partner by an- It has taken a long time for biologists gener- other taxon with different traits (Koga et al. ally to appreciate the significance of associa- 2013; Toju et al. 2013). With the dramatically tions with symbiotic microorganisms for eu- improving genomic technologies, it is becom- karyotes. Despite the discovery of the dual ing increasingly feasible to answer these funda- nature of lichens (fungi and algae/cyanobacte- mental questions. ria) and near-ubiquitous associations between We should also recognize that most current plant roots and mycorrhizal fungi in the 1800s, research is focused on a tiny subset of the di- symbioses were treated as mere curiosities of versity of symbioses, notably a few phyla of Eu- nature through much of the last century. The bacteria associated with animals, especially hu- overwhelming molecular evidence for bacterial mans and laboratory mice. A major outstanding origins of mitochondria and plastids, together issue is the taxonomic and functional diversity with the realization that the resident microbio- of symbioses across the evolutionary radiation ta is vital for the human health and productivi- of eukaryotes. In particular, relatively little is ty of crops and livestock has, at last, placed sym- known about symbioses involving protists as biosis in the mainstream of biology. And yet, either host or symbiont, even though the pro- multiple questions central to our understand- tists account for most of the evolutionary diver- ing of the function and evolution of symbioses sity of eukaryotes. Some of these associations remain. are apparently without parallel in animals or Tremendous opportunities are being pro- plants, for example, motility conferred on large vided by the latest sequencing technologies. Al- protists by spirochete ectosymbionts (Cleveland though currently used mostly to catalog the and Grimstone 1964), and protection from composition and activities of bacterial com- predators by extrusive structures associated munities (Human Microbiome Project 2012b), with bacterial symbionts of the ciliate Euplodi- these methods are starting to be applied to in- nium (Petroni et al. 2000). Reinvigorated re- vestigate both the diversity of eukaryotic micro- search on symbioses involving protists has the bial symbionts and how microbial communities potential to expand and modify our concept of are structured (Costello et al. 2012). A key un- the general principles of symbiosis. resolved question is whether the functional traits of resident microorganisms can be pre- ACKNOWLEDGMENTS dicted from their taxonomic composition. Perhaps such a relationship is frequently con- This work is supported by NIH grant founded by microbe–microbe and microbe– 1R01GM095372-01, NSF grant BIO 1241099, host interactions, resulting in spatiotemporal and the Sarkaria Institute for Insect Physiology variation in the traits of microorganisms. Re- and Toxicology.

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 9 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

REFERENCES Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, Adams AS, Jordan MS, Adams SM, Suen G, Goodwin LA, O’Sullivan O, et al. 2012. Gut microbiota composition Davenport KW, Currie CR, Raffa KF. 2011. Cellulose-de- correlates with diet and health in the elderly. Nature 488: grading bacteria associated with the invasive woodwasp 178–184. Sirex noctilio. ISME J 5: 1323–1331. Cleveland LR, Grimstone AV.1964. The fine structure of the Adams AS, Aylward FO, Adams SM, Erbilgin N, Aukema flagellate Mixotricha paradoxa and its associated micro- BH, Currie CR, Suen G, Raffa KF. 2013. Mountain pine organisms. Proc Roy Soc London B 159: 668–686. beetles colonizing historical and naive host trees are as- Corby HDL, Smith DL, Sprent JI. 2011. Size, structure and sociated with a bacterial community highly enriched in nitrogen content of seeds of Fabaceae in relation to nod- genes contributing to terpene metabolism. Appl Environ ulation. Bot J Lin Soc 167: 251–280. Microbiol 79: 3468–3475. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Rel- Alegado RA, Brown LW, Cao S, Dermenjian RK, Zuzow R, man DA. 2012. The application of ecological theory to- Fairclough SR, Clardy J, King N. 2012. Bacterial regula- ward an understanding of the human microbiome. Sci- tion of colony development in the closest living relatives ence 336: 1255–1262. of animals. eLife 1: e00013. Danovaro R, Dell’Anno A, Pusceddu A, Gambi C, Heiner I, Altincicek B, Kovacs JL, Gerardo NM. 2012. Horizontally Kristensen RM. 2010. The first metazoa living in perma- transferred fungal carotenoid genes in the two-spotted nently anoxic conditions. BMC Biol 8: 30. spider mite Tetranychus urticae. Biol Lett 8: 253–257. Davison A, Blaxter M. 2005. Ancient origin of glycosyl hy- Berenbaum MR. 1988. Micro-organisms as mediators of drolase family 9 cellulase genes. Mol Biol Evol 22: 1273– intertrophic and intratrophic interactions. In Novel as- 1284. pects of insect–plant interactions (ed. Barbosa P, Letour- De Fine Licht HH, Schiott M, Rogowska-Wrzesinska A, neau DK), pp. 91–123. Wiley, New York. Nygaard S, Roepstorff P, Boomsma JJ. 2013. Laccase de- Bhavsar AP, Guttman JA, Finlay BB. 2007. Manipulation of toxification mediates the nutritional alliance between host-cell pathways by bacterial pathogens. Nature 449: leaf-cutting ants and fungus-garden symbionts. Proc 827–834. Natl Acad Sci 110: 583–587. Blaser MJ, Falkow S. 2009. What are the consequences of the de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, disappearing human microbiota? Nat Rev Microbiol 7: Raybould HE. 2010. Propensity to high-fat diet-induced 887–894. obesity in rats is associated with changes in the gut micro- Bourne DG, Dennis PG, Uthicke S, Soo RM, Tyson GW, biota and gut inflammation. Am J Physiol 299: G440– Webster N. 2013. Coral reef invertebrate microbiomes G448. correlate with the presence of photosymbionts. ISME J Desai MS, Brune A. 2012. Bacteroidales ectosymbionts of 7: 1459. gut flagellates shape the nitrogen-fixing community in Bravo JA, Forsythe P,Chew MV,Escaravage E, Savignac HM, dry-wood termites. ISME J 6: 1302–1313. Dinan TG, Bienenstock J, Cryan JF. 2011. Ingestion of Despres L, David JP, Gallet C. 2007. The evolutionary ecol- Lactobacillus strain regulates emotional behavior and ogy of insect resistance to plant chemicals. Trends Ecol central GABA receptor expression in a mouse via the Evol 22: 298–307. vagus nerve. Proc Natl Acad Sci 108: 16050–16055. Dillon RJ, Dillon VM. 2004. The gut bacteria of insects: Brucker RM, Bordenstein SR. 2013. The hologenomic basis Nonpathogenic interactions. Annu Rev Entomol 49: 71– of speciation: Gut bacteria cause hybrid lethality in the 92. genus Nasonia. Science 341: 667–669. Dobbelaere S, Croonenburghs A, Thys A, Vande Broek A, Buchner P. 1965. Endosymbioses of animals with plant mi- Vanderleyden J. 1999. Phytostimulatory effect of Azospi- croorganisms. Wiley, Chichester, UK. rillum brasilense wild type and mutant strains altered in IAA production on wheat. Plant Soil 212: 155–164. Calderon-Cortes N, Quesada M, Watanabe H, Cano-Cama- cho H, Oyama K. 2012. Endogenous plant cell wall di- Douglas AE. 2009. The microbial dimension in insect nu- gestion: A key mechanism in insect evolution. Annu Rev tritional ecology. Funct Ecol 23: 38–47. Ecol Evol Syst 43: 45–71. Douglas AE. 2010. The symbiotic habit. Princeton University Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Loz- Press, Princeton, NJ. upone CA, Turnbaugh PJ, Fierer N, Knight R. 2011. Embley TM, Martin W.2006. Eukaryotic evolution, changes Global patterns of 16S rRNA diversity at a depth of mil- and challenges. Nature 440: 623–630. lions of sequences per sample. Proc Natl Acad Sci 108: Finan TM. 2002. Evolving insights: Symbiosis islands and 4516–4522. horizontal gene transfer. JBac184: 2855–2856. Cheeke PR. 1994. A review of the functional and evolution- Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, ary roles of the liver in the detoxification of poisonous Schoenfeld D, Nomicos E, Park M, NIH Intramural plants, with special reference to pyrrolizidine alkaloids. Sequencing Center Comparative Sequencing Program, Vet Hum Toxicol 36: 240–247. et al. 2013. Topographic diversity of fungal and bacterial Cho I, YamanishiS, Cox L, Methe´ BA, Zavadil J, Li K, Gao Z, communities in human skin. Nature 498: 367–370. Mahana D, Raju K, Teitler I, et al. 2012. Antibiotics in Fletcher LR, Harvey IC. 1981. An association of a Lolium early life alter the murine colonic microbiome and adi- endophyte with ryegrass staggers. New Zeal VetJ 29: 185– posity. Nature 488: 621–626. 186.

10 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

Foster RA, Kuypers MM, Vagner T, Paerl RW, Musat N, Kellner RL. 2001. Suppression of pederin biosynthesis Zehr JP. 2011. Nitrogen fixation and transfer in through antibiotic elimination of endosymbionts in Pae- open ocean diatom–cyanobacterial symbioses. ISME J derus sabaeus. J Insect Physiol 47: 475–483. 5: 1484–1493. Koga R, Bennett GM, Cryan JR, Moran NA. 2013. Evolu- Gandon S, Agnew P, Michalakis Y. 2002. Coevolution be- tionary replacement of obligate symbionts in an ancient tween parasite virulence and host life-history traits. Am and diverse insect lineage. Environ Microbiol 15: 2037– Nat 160: 374–388. 2081. Geib SM, Filley TR, Hatcher PG, Hoover K, Carlson JE, del Kremer N, Voronin D, Charif D, Mavingui P, Mollereau B, Mar Jimenez-Gasco M, Nakagawa-Izumi A, Sleighter RL, Vavre F. 2009. Wolbachia interferes with ferritin expres- Tien M. 2008. Lignin degradation in wood-feeding in- sion and iron metabolism in insects. PLoS Pathog 5: sects. Proc Natl Acad Sci 105: 12932–12937. e1000630. Gill EE, Brinkman FS. 2011. The proportional lack of Kwan JC, Donia MS, Han AW, Hirose E, Haygood MG, archaeal pathogens: Do viruses/phages hold the key? Schmidt EW. 2012. Genome streamlining and chemical Bioessays 33: 248–254. defense in a coral reef symbiosis. Proc Natl Acad Sci 109: 20655–20660. Hadfield MG. 2011. Biofilms and marine invertebrate larvae: What bacteria produce that larvae use to choose Lane N, Martin W. 2010. The energetics of genome com- settlement sites. Annu Rev Mar Sci 3: 453–470. plexity. Nature 467: 929–934. Haiser HJ, Turnbaugh PJ. 2012. Is it time for a metagenomic Lasken RS. 2013. Single-cell sequencing in its prime. Nature basis of therapeutics? Science 336: 1253–1255. Biotechnol 31: 211–212. Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus Lechene CP, Luyten Y, McMahon G, Distel DL. 2007. EP, Turnbaugh PJ. 2013. Predicting and manipulating Quantitative imaging of nitrogen fixation by indi- cardiac drug inactivation by the human gut bacterium vidual bacteria within animal cells. Science 317: 1563– Eggerthella lenta. Science 341: 295–298. 1566. Hjort K, Goldberg AV, Tsaousis AD, Hirt RP, Embley TM. Lugtenberg B, Kamilova F. 2009. Plant-growth-promoting 2010. Diversity and reductive evolution of mitochondria rhizobacteria. Annu Rev Microbiol 63: 541–556. among microbial eukaryotes. Philos Trans R Soc Lond B Lundberg DS, Lebeis SL, Paredes SH, Yourstone S, Gehring J, Biol Sci 365: 713–727. Malfatti S, Tremblay J, Engelbrektson A, Kunin V,del Rio TG, et al. 2012. Defining the core Arabidopsis thaliana Holmes E, Kinross J, Gibson GR, Burcelin R, Jia W, Petters- root microbiome. Nature 488: 86–90. son S, Nicholson JK. 2012. Therapeutic modulation of microbiota–host metabolic interactions. Sci Trans Med Maslowski KM, Mackay CR. 2011. Diet, gut microbiota and 4: 136–137. immune responses. Nat Immunol 12: 5–9. Houlton BZ, Wang YP, Vitousek PM, Field CB. 2008. A Matsumoto M, Ishige A, Yazawa Y,Kondo M, Muramatsu K, unifying framework for dinitrogen fixation in the terres- Watanabe K. 2012. Promotion of intestinal peristalsis by trial biosphere. Nature 454: 327–330. Bifidobacterium spp. capable of hydrolysing sennosides in mice. PLoS ONE 7: e31700. Hughes DP, Brodeur J, Thomas F. 2012. Host manipulation by parasites. Oxford University Press, Oxford. Maynard CL, Elson CO, Hatton RD, Weaver CT. 2012. Re- ciprocal interactions of the intestinal microbiota and im- Human Microbiome Project Consortium. 2012a. Structure, mune system. Nature 489: 231–241. function and diversity of the healthy human micro- McFall-Ngai M, Hadfield MG, Bosch TC, Carey HV,Doma- biome. Nature 486: 207–214. zet-Loso T, Douglas AE, Dubilier N, Eberl G, Fukami T, Human Microbiome Project Consortium. 2012b. A frame- Gilbert SF,et al. 2013. Animals in a bacterial world, a new work for human microbiome research. Nature 486: imperative for the life sciences. Proc Natl Acad Sci 110: 215–221. 3229–3236. Iliev ID, Funari VA,Taylor KD, Nguyen Q, Reyes CN, Strom Metchnikoff E. 1910. The prolongation of life: Optimistic SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, et al. studies. Heinemann, Portsmouth, NH. 2012. Interactions between commensal fungi and the Moran NA, Jarvik T. 2010. Lateral transfer of genes from C-type lectin receptor Dectin-1 influence colitis. Science fungi underlies carotenoid production in aphids. Science 336: 1314–1317. 328: 624–627. Joint I, Tait K, Callow ME, Callow JA, Milton D, Williams Muegge BD, Kuczynski J, Knights D, Clemente JC, Gonzalez P, Camara M. 2002. Cell-to-cell communication across A, Fontana L, Henrissat B, Knight R, Gordon JI. 2011. the prokaryote–eukaryote boundary. Science 298: 1207. Diet drives convergence in gut microbiome functions Jones CG. 1984. Microorganisms as mediators of plant re- across mammalian phylogeny and within humans. Sci- source exploitation by insect herbivores. In A new ecology: ence 332: 970–974. Novel approaches to interactive systems (ed. Price PW, Nakayama T, Ishida K. 2009. Another acquisition of a pri- et al.), pp. 53–99. Wiley, New York. mary photosynthetic organelle is underway in Paulinella Karasov WH, Douglas AE. 2013. Comparative digestive chromatophora. Curr Biol 19: R284–R285. physiology. Compr Physiol 3: 741–783. Novakova E, Moran NA. 2012. Diversification of genes Keeling PJ. 2013. The number, speed, and impact of plastid for carotenoid biosynthesis in aphids following an endosymbioses in eukaryotic evolution. Annu Rev Plant ancient transfer from a fungus. Mol Biol Evol 29: 313– Biol 64: 583–607. 323.

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 11 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

A.E. Douglas

Nowack EC, Grossman AR. 2012. Trafficking of protein into Sharp KH, Davidson SK, Haygood MG. 2007. Localization the recently established photosynthetic organelles of Pau- of “Candidatus Endobugula sertula” and the bryostatins linella chromatophora. Proc Natl Acad Sci 109: 5340– throughout the life cycle of the bryozoan Bugula neritina. 5345. ISME J 1: 693–702. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, Shin SC, Kim S-H, You H, Kim B, Kim AC, Lee K-A, Yoon Glickman JN, Siebert R, Baron RM, Kasper DL, et al. J-H, Ryu J-H, Lee W-J. 2011. Drosophila microbiome 2012. Microbial exposure during early life has persistent modulates host developmental and metabolic homeosta- effects on natural killer T cell function. Science 336: 489– sis via insulin signaling. Science 334: 670–674. 493. Sloan DB, Moran NA. 2013. The evolution of genomic in- Pamp SJ, Harrington ED, Quake SR, Relman DA, Blainey stability in the obligate endosymbionts of whiteflies. Ge- PC. 2012. Single-cell sequencing provides clues about the nome Biol Evol 5: 783–793. host interactions of segmented filamentous bacteria Smith K, McCoy KD, Macpherson AJ. 2007. Use of axe- (SFB). Genome Res 22: 1107–1119. nic animals in studying the adaptation of mammals to Pannebakker BA, Loppin B, Elemans CP,Humblot L, Vavre their commensal intestinal microbiota. Sem Immunol 19: F. 2007. Parasitic inhibition of cell death facilitates sym- 59–69. biosis. Proc Natl Acad Sci 104: 213–215. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya Pernice M, Meibom A, VanDen Heuvel A, Kopp C, Domart- R, Cheng J, Kau AL, Rich SS, Concannon P, Mycha- Coulon I, Hoegh-Guldberg O, Dove S. 2012. A single-cell leckyj JC, et al. 2013. Gut microbiomes of Malawian view of ammonium assimilation in coral–dinoflagellate twin pairs discordant for kwashiorkor. Science 339: symbiosis. ISME J 6: 1314–1324. 548–554. Petersen JM, Zielinski FU, Pape T, Seifert R, Moraru C, Spaepen S, Versees W, Gocke D, Pohl M, Steyaert J, Vander- Amann R, Hourdez S, Girguis PR, Wankel SD, Barbe V, leyden J. 2007. Characterization of phenylpyruvate decar- et al. 2011. Hydrogen is an energy source for hydrother- boxylase, involved in auxin production of Azospirillum mal vent symbioses. Nature 476: 176–180. brasilense. J Bacteriol 189: 7626–7633. Petroni G, Spring S, Schleifer K-H, Verni F, Rosati G. 2000. Spiering MJ, Moon CD, Wilkinson HH, Schardl CL. 2005. Defensive extrusive ectosymbionts of Euplotidium (Cil- Gene clusters for insecticidal loline alkaloids in the iophora) that contain microtubule-like structures are grass–endophytic fungus Neotyphodium uncinatum. Ge- bacteria related to Verrucomicrobia. Proc Natl Acad Sci netics 169: 1403–1414. 97: 1813–1817. Stappenbeck TS, Hooper LV, Gordon JI. 2002. Develop- Piel J, Hofer I, Hui D. 2004a. Evidence for a symbiosis island mental regulation of intestinal angiogenesis by indigen- involved in horizontal acquisition of pederin biosyn- ous microbes via Paneth cells. Proc Natl Acad Sci 99: thetic capabilities by the bacterial symbiont of Paederus 15451–15455. fuscipes beetles. J Bacteriol 186: 1280–1286. Stecher B, Maier L, Hardt WD. 2013. “Blooming” in the gut: Piel J, Hui D, Wen G, Butzke D, Platzer M, Fusetani N, How dysbiosis might contribute to pathogen evolution. Matsunaga S. 2004b. Antitumor polyketide biosynthesis Nat Rev Microbiol 11: 277–284. by an uncultivated bacterial symbiont of the marine Steenhoudt O, Vanderleyden J. 2000. Azospirillum, a free- sponge Theonella swinhoei. Proc Natl Acad Sci 101: living nitrogen-fixing bacterium closely associated with 16222–16227. grasses: Genetic, biochemical and ecological aspects. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh FEMS Microbiol Rev 24: 487–506. C, Nielsen T, Pons N, Levenez F, Yamada T, et al. 2010. A Strachan DP. 1989. Hay fever, hygiene, and household size. human gut microbial gene catalogue established by meta- Brit Med J 299: 1259–1260. genomic sequencing. Nature 464: 59–65. Suen G, Scott JJ, Aylward FO, Adams SM, Tringe SG, Pin- Roca A, Pizarro-Tobias P, Udaond Z, Fernańdez M, Matilla to-TomasAA, Foster CE, Pauly M, WeimerPJ, Barry KW, MA, Molina-Henares MA, Molina L, Segura A, Duque E, et al. 2010. An insect herbivore microbiome with Ramos JL. 2013. Analysis of the plant growth-promoting high plant biomass-degrading capacity. PLoS Genet 6: properties encoded by the genome of the rhizobacterium e1001129. Pseudomonas putida BIRD-1. Environ Microbiol 15: 780– Sundset MA, Kohn A, Mathiesen SD, Praesteng KE. 794. 2008. Eubacterium rangiferina, a novel usnic acid-resis- Roeselers G, Newton IL. 2012. On the evolutionary ecology tant bacterium from the reindeer rumen. Naturwiss 95: of symbioses between chemosynthetic bacteria and bi- 741–749. valves. Appl Microbiol Biotechnol 94: 1–10. Sundset MA, Barboza PS, Green TK, Folkow LP, Blix AS, Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Maz- Mathiesen SD. 2010. Microbial degradation of usnic acid manian SK. 2011. The Toll-like receptor 2 pathway estab- in the reindeer rumen. Naturwiss 97: 273–278. lishes colonization by a commensal of the human micro- Toju H, Tanabe AS, Notsu Y,Sota T, Fukatsu T. 2013. Diver- biota. Science 332: 974–977. sification of endosymbiosis: Replacements, co-speciation Sachs JL, Skophammer RG, Regus JU. 2011. Evolutionary and promiscuity of bacteriocyte symbionts in weevils. transitions in bacterial symbiosis. Proc Natl Acad Sci 108: ISME J 7: 1378–1390. 10800–10807. van der Giezen M, Tovar J, Clark CG. 2005. Mitochondrion- Schulz HN, Jorgensen BB. 2001. Big bacteria. Annu Rev derived organelles in protists and fungi. Int Rev Cytol 244: Microbiol 55: 105–137. 175–225.

12 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis in Eukaryotic Evolution

Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Williams KP,Sobral BW,Dickerman AW.2007. A robust spe- Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley cies tree for the a-proteobacteria. JBac189: 4578–4586. RE, Gewirtz AT. 2010. Metabolic syndrome and altered Zaneveld JR, Parfrey LW, Van Treuren W, Lozupone C, Cle- gut microbiota in mice lacking Toll-like receptor 5. Sci- mente JC, Knights D, Stombaugh J, Kuczynski J, Knight ence 328: 228–231. R. 2011. Combined phylogenetic and genomic approach- WagnerA. 2005. Energy constraints on the evolution of gene es for the high-throughput study of microbial habitat expression. Mol Biol Evol 22: 1365–1374. adaptation. Trends Microbiol 19: 472–482.

Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016113 13 Downloaded from http://cshperspectives.cshlp.org/ on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press

Symbiosis as a General Principle in Eukaryotic Evolution

Angela E. Douglas

Cold Spring Harb Perspect Biol 2014; doi: 10.1101/cshperspect.a016113

Subject Collection The Origin and Evolution of Eukaryotes

The Persistent Contributions of RNA to Eukaryotic Origins: How and When Was the Eukaryotic Gen(om)e Architecture and Cellular Mitochondrion Acquired? Function Anthony M. Poole and Simonetta Gribaldo Jürgen Brosius Green Algae and the Origins of Multicellularity in Bacterial Influences on Animal Origins the Plant Kingdom Rosanna A. Alegado and Nicole King James G. Umen The Archaeal Legacy of Eukaryotes: A Missing Pieces of an Ancient Puzzle: Evolution of Phylogenomic Perspective the Eukaryotic Membrane-Trafficking System Lionel Guy, Jimmy H. Saw and Thijs J.G. Ettema Alexander Schlacht, Emily K. Herman, Mary J. Klute, et al. Origin and Evolution of the Self-Organizing The Neomuran Revolution and Phagotrophic Cytoskeleton in the Network of Eukaryotic Origin of Eukaryotes and Cilia in the Light of Organelles Intracellular Coevolution and a Revised Tree of Gáspár Jékely Life Thomas Cavalier-Smith On the Age of Eukaryotes: Evaluating Evidence Protein Targeting and Transport as a Necessary from Fossils and Molecular Clocks Consequence of Increased Cellular Complexity Laura Eme, Susan C. Sharpe, Matthew W. Brown, Maik S. Sommer and Enrico Schleiff et al. Origin of Spliceosomal Introns and Alternative How Natural a Kind Is ''Eukaryote?'' Splicing W. Ford Doolittle Manuel Irimia and Scott William Roy Protein and DNA Modifications: Evolutionary What Was the Real Contribution of Imprints of Bacterial Biochemical Diversification Endosymbionts to the Eukaryotic Nucleus? and Geochemistry on the Provenance of Insights from Photosynthetic Eukaryotes Eukaryotic Epigenetics David Moreira and Philippe Deschamps L. Aravind, A. Maxwell Burroughs, Dapeng Zhang, et al.

For additional articles in this collection, see http://cshperspectives.cshlp.org/cgi/collection/

The Eukaryotic Tree of Life from a Global Bioenergetic Constraints on the Evolution of Phylogenomic Perspective Complex Life Fabien Burki Nick Lane

For additional articles in this collection, see http://cshperspectives.cshlp.org/cgi/collection/