atmospheric composition on Earth today Evolutionary microbiology differ markedly from those that existed when life first emerged on this planet more than four billion years ago. During what is known as the Great Oxidation Event, around 2.1 bil- A microbial marriage lion years ago5, oxygen accumulated in the atmosphere and oceanic waters, a develop- forged in nitrate ment that had a major bearing on the course of life on Earth. Oxygen is toxic to most organ- William H. Lewis & Thijs J. G. Ettema isms that thrive in environments devoid of it. However, some micro organisms learnt to Symbiotic interactions between organisms have aided harness oxygen’s chemical properties, using major evolutionary transitions. The interaction between it as an electron acceptor in energy-generating two microorganisms has parallels with the evolution of pathways. This type of oxygen-dependent pro- cess, called aerobic respiration, is much more mitochondria — key organelles in eukaryotic cells. See p.445 energy-efficient than fermentation, a form of non-oxygen-dependent energy metabolism of ancient origin, which enables many anaerobic In the vast diversity of microbial life, numerous an endosymbiosis in which a host cell belong- organisms to survive without oxygen. examples exist of symbiosis — a process ing to a group of single-celled organisms called Eukaryotic cells probably arose sometime whereby different organisms maintain a stable Asgard archaea2,3 took up a type of bacterial cell after the Great Oxidation Event6, and their relationship with one another. Such inter- that belonged to the phylum Proteo bacteria4. ability to perform aerobic respiration was actions generally offer some form of benefit Mitochondria in eukaryotic cells are consid- acquired through the mitochondrial endo- to one or more of the organisms involved. Graf ered to be the direct descendants of these once- symbiont. The capacity for efficient energy et al.1 report on page 445 the discovery of an free-living proteobacterial endosymbionts. production that this provided is thought to intriguing example of symbiosis between Graf and colleagues describe an intriguing have conferred selective advantages during microorganisms. This finding might shed light bacterial endosymbiont that they discov- eukaryotic evolution, although the exact con- on the types of process that led to the evolu- ered living in a ciliate, a type of eukaryotic, tribution to, for example, the emergence of tion of mitochondria, the energy-producing single-celled microbe. Although associa- cellular complexity is debated7. organelles found in eukaryotic cells (those tions between these types of organism are not Current evidence6 indicates that early eukar- containing a nucleus). uncommon, this particular case has some of yote evolution and diversification occurred In some cases, symbiotic partners can the hallmarks of the type of endosymbiosis under conditions in which oxygen was pres- become integrated in such a way that one part- that gave rise to mitochondria. That includes ent. However, some groups of eukaryotes ner is taken up into the cell of the other part- the production of energy in the form of ATP nevertheless thrive in environments devoid ner by a process called endosymbiosis (Fig. 1). molecules by the energy-generating process of oxygen. These anaerobic eukaryotes are Endosymbiotic interactions have enabled key known as respiration. This process is also con- thought to have evolved from aerobic mito- transitions during the history of life on Earth. A nected to a mechanism by which ATP might be chondrion-bearing ancestors. prime example of this is thought to be the inter- exported from the endosymbiont to provide In the absence of oxygen, the anaerobic action that gave rise to the first eukaryotic cell. the host with energy. eukaryotes use a fermentation-based metab- This ancestral eukaryote probably formed from The environmental conditions and olism, which subjects them to more-stringent a b Last ciliate c Anaerobic common ancestor ciliate Hydrogenosome Asgard ATP Ciliate from Last eukaryotic O2 archaeal + H2O ATP common ancestor H+ Lake Zug host cell Aerobic respiration + H2 Mitochondrion using an ETC Fermentation ATP H+ + H2 ATP Eukaryotic Endosymbiosis O2 ATP + H2O diversification Endosymbiosis Nitrate + N Aerobic respiration 2 Anaerobic respiration using an ETC Other using an ETC Free-living lineages proteobacterial Free-living ancestor of mitochondria Gammaproteobacterium Figure 1 | Organelle evolution. a, Eukaryotic cells, those with a nucleus adapted to thrive in environments without oxygen. The mitochondria of these (nucleus not shown), probably arose when a type of single-celled host called ciliates have evolved into organelles called hydrogenosomes. Anaerobic ciliates an Asgard archaeal cell2,3 took up a proteobacterial cell in a process called carry out fermentation, a process in which ATP is generated and hydrogen ions 4 + 1 endosymbiosis . The proteobacterium evolved to form mitochondrial (H ) gain electrons to form hydrogen (H2). Graf et al. report the discovery of an organelles in the last common ancestor of all eukaryotes. Through the anaerobic ciliate with a gammaproteobacterial endosymbiont. This bacterium’s process of aerobic respiration, in which oxygen (O2) is consumed and water is genome encodes the components needed to generate ATP by converting nitrate formed as electrons are transferred along an electron-transport chain (ETC), a to nitrogen (N2) using anaerobic respiration, and to export ATP to the host. mitochondrion produces energy in the form of ATP molecules. b, Eukaryotes This finding reveals how anaerobic ciliates can regain the ability to carry out diversified, and only some lineages, such as the last common ancestor of respiration using an ETC. These features are similar to processes associated with organisms called ciliates, retained mitochondria. c, Some lineages of ciliate mitochondrial evolution. Nature | Vol 591 | 18 March 2021 | 375 ©2021 Spri nger Nature Li mited. All ri ghts reserved. ©2021 Spri nger Nature Li mited. All ri ghts reserved. News & views energy regimes than those of aerobic eukar- mitochondria in eukaryotes. In both cases, res- production, has been replaced or retained in yotes. This kind of metabolism has arisen in piratory capacity was acquired by an anaerobic the ciliate’s hydrogenosomes. Evidence indicat- various types of anaerobic eukaryote, and is host cell through the metabolic integration of ing that the ATP transporter identified by Graf associated with the evolution of mitochon- a proteobacterial endosymbiont, and mecha- and colleagues can export ATP to the ciliate host dria into organelles called hydrogenosomes8. nisms can be identified for energy exchange would help to confirm the proposed symbiotic All hydrogenosomes have, to some degree, between symbiont and host cell. Furthermore, interaction. Further discovery and exploration lost mitochondrial pathways for aerobic res- a substantial reduction of the endosymbiont of similarly surprising symbiotic interactions in piration, and generate hydrogen rather than genome is observed, although mitochondrial poorly explored parts of the microbial world is carbon dioxide and water as an end product genomes are typically either much smaller than certainly an exciting prospect for the future. of their energy-generating pathways. Ciliates the endosymbiont genome observed by Graf are exceptionally effective at adapting to oxy- and colleagues, or have been lost completely William H. Lewis and Thijs J. G. Ettema are in gen-depleted environments, and mitochon- (as is the case for several hydrogenosomes10). the Laboratory of Microbiology, Wageningen drion-to-hydrogenosome transitions have Despite these fascinating similarities, there University and Research, NL-6708 WE occurred independently several times in this are also notable differences. Mitochondrial Wageningen, the Netherlands. W.H.L. is also in group of organisms9. endosymbiosis was a much more ancient the Department of Biochemistry, University of Graf and colleagues investigated an anaero- event, enlisting an archaeal host cell rather Cambridge, Cambridge, UK. bic ciliate belonging to the class Plagiopylea, than a modern eukaryotic cell. Mitochondria, e-mails: [email protected]; found in the deepest layers of Lake Zug in even if now reduced from their original form, [email protected] Switzerland. This environment lacks oxygen or even lost from some present-day eukar- 11 and contains relatively high levels of nitrate. yotes , became an integral part of eukary- 1. Graf, J. S. et al. Nature 591, 445–450 (2021). An initial assessment using microscopy otic cells. Genes inherited from the original 2. Eme, L., Spang, A., Lombard, J., Stairs, C. W. & revealed that, unusually, these ciliates have mitochondrial endosymbiont were often re­­ Ettema, T. J. G. Nature Rev. Microbiol. 15, 711–723 (2017). 3. Zaremba-Niedzwiedzka, K. et al. Nature 541, 353–358 a bacterial endosymbiont (belonging to the targeted to the nuclear genome, and some of (2017). class Gamma proteobacteria), rather than an the proteins these genes encoded adopted var- 4. Roger, A. J., Muñoz-Gómez, S. A. & Kamikawa, R. archaeal endosymbiont that produces meth- ious functions throughout the cell. A similar Curr. Biol. 27, R1177–R1192 (2017). 5. Lyons, T. W., Reinhard, C. T. & Planavsky, N. J. Nature 506, ane, which is the more typical type of endo- level of integration is unlikely for the bacterial 307–315 (2014). symbiont present in anaerobic ciliates. endosymbionts of the ciliate