Current Biology Dispatches researchers a molecular foothold into mechanisms underlying the activation of the hygroreceptor as well as the encoding of humidity in the brain. Additional work will be necessary to determine whether hygrosensory neurons outside the sacculus [8,15], like the ones expressing waterwitch or nanchung, represent a parallel class of hygrosensory neurons that supplement saccular responses. Molecular identification of all three receptors in the hygrosensory triad will permit the exploration of biophysical principles underlying activation of the hygroreceptor. This will also generate tools to explore other compelling questions such as how humidity and temperature information interact in the brain and how the relevant neural circuits determine humidity set-points in different Drosophila species. REFERENCES 1. Tichy, H. (1987). Hygroreceptor identification and response characteristics in the stick insect Carausius morosus. J. Comp. Physiol. A 160, 43–53. 2. Altner, H., and Loftus, R. (1985). Ultrastructure and function of insect thermo- And hygroreceptors. Annu. Rev. Entomol. 30, 273–295. 3. Yokohari, F. (1978). Hygroreceptor mechanism in the antenna of the cockroach Periplaneta. J. Comp. Physiol. A 124, 53–60. 4. Enjin, A., Zaharieva, E.E., Frank, D.D., Mansourian, S., Suh, G.S.B., Gallio, M., and Stensmyr, M.C. (2016). Humidity sensing in Drosophila. Curr. Biol. 26, 1352–1358. 5. Bentley, I.M. (1900). The synthetic experiment. Am. J. Psychol. 11, 405. 6. Filingeri, D., and Havenith, G. (2015). Human skin wetness perception: psychophysical and neurophysiological bases. Temperature 2, 86–104. 7. Russell, J., Vidal-Gadea, A.G., Makay, A., Lanam, C., and Pierce-Shimomura, J.T. (2014). Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 111, 8269–8274. 8. Liu, L., Li, Y., Wang, R., Yin, C., Dong, Q., Hing, H., et al. (2007). Drosophila hygrosensation requires the TRP channels water witch and nanchung. Nature 450, 294–298. 9. Sayeed, O., and Benzer, S. (1996). Behavioral genetics of thermosensation and hygrosensation in Drosophila. Proc. Natl. Acad. Sci. USA 93, 6079–6084. 10. Abuin, L., Bargeton, B., Ulbrich, M.H., Isacoff, E.Y., Kellenberger, S., and Benton, R. (2011). Functional architecture of olfactory ionotropic glutamate receptors. Neuron 69, 44–60. 11. Larsson, M.C., Domingos, A.I., Jones, W.D., Chiappe, M.E., Amrein, H., and Vosshall, L.B. (2004). Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43, 703–714. 12. Shanbhag, S.R., Singh, K., and Singh, R.N. (1995). Fine structure and primary sensory projections of sensilla located in the sacculus of the antenna of Drosophila melanogaster. Cell Tissue Res. 282, 237–249. 13. Silbering, A.F., Rytz, R., Grosjean, Y., Abuin, L., Ramdya, P., Jefferis, G.S.X.E., et al. (2011). Complementary function and integrated wiring of the evolutionarily distinct Drosophila olfactory subsystems. J. Neurosci. 31, 13357–13375. 14. Su, C.-Y., Menuz, K., Reisert, J., and Carlson, J.R. (2012). Non-synaptic inhibition between grouped neurons in an olfactory circuit. Nature 492, 66–71. 15. Yao, C.A., Ignell, R., and Carlson, J.R. (2005). Chemosensory coding by neurons in the coeloconic sensilla of the Drosophila antenna. J. Neurosci. 25, 8359–8367. Mitochondrial Evolution: Going, Going, Gone Fabien Burki Science for Life Laboratory, Program in Systematic Biology, Department of Organismal Biology, Uppsala University, Norbyvägen 18D, 75236 Uppsala, Sweden Correspondence: fabien.burki@ebc.uu.se http://dx.doi.org/10.1016/j.cub.2016.04.032 Monocercomonoides is the first example of a eukaryote lacking even the most reduced form of a mitochondrion-related organelle. This has important implications for cellular processes and our understanding of reductive mitochondrial evolution across the eukaryotic tree of life. The origin of mitochondria by the endosymbiotic integration of an a-proteobacterium is one of the defining events in eukaryote evolution. Although the details of this endosymbiosis are still unclear [1,2], more than two decades of molecular evolution and cell biology research have demonstrated that the origin of mitochondria predated the divergence of all known eukaryotes. This means that all extant eukaryotes, or at least their ancestral lineages, are predicted to harbor mitochondria in one way or another. And indeed, all species studied to date have been found with either canonical aerobic mitochondria, or less conventional but evolutionarily linked mitochondrionrelated organelles (MROs) in anaerobic and microaerophilic lineages (Figure 1). MROs are loosely defined as degenerated mitochondria exhibiting various degrees R410 Current Biology 26, R408–R431, May 23, 2016 of reduction. They represent a continuum from anaerobic mitochondria (generate ATP using alternative electron acceptors), to more reduced hydrogenosomes (generate ATP via substrate-level phosphorylation, lack an electron transport chain, produce hydrogen), to highly reduced mitosomes (no role in ATP production, lack an electron transport chain, involved in iron-sulfur cluster assembly) [3,4]. So all extant Current Biology Dispatches eukaryotes possess organelles related to mitochondria, right? Not anymore, as we are told by Karnkowska and colleagues in this issue of Current Biology [5], reporting on the recent genome sequencing of the anaerobic microbe Monocercomonoides sp. Demonstrating absence is a daunting task. To provide a compelling case for the complete lack of mitochondrial organelles in Monocercomonoides sp., Karnkowska et al. set out on a range of bioinformatic experiments. First, they show that their draft genome is virtually complete. With that in hand, they confirm that no mitochondrial genome is to be found, which comes as little surprise, as many MROs lost their genome long ago, and mitochondrial metabolism in general is sustained by proteins encoded in the nucleus [6]. Some of these nucleus-encoded proteins represent hallmarks of mitochondrial function, and are typically associated with MROs in other organisms. These include the homologous core of the protein import machinery, transporters of the mitochondrial carrier family, or the mitochondrial iron-sulfur (Fe-S) cluster assembly [7]. Not in Monocercomonoides sp., which lacks all of them. To be comprehensive, the authors also looked at a larger database of known mitochondrial proteins, and expanded their hunt beyond homology searches to look for signature sequence motifs such as mitochondrial targeting signals. Needless to say, none of these approaches came back positive, allowing Karnkowska et al. to infer the general absence of mitochondrial proteins in Monocercomonoides sp., and by extension the unprecedented report of a eukaryote without any kinds of mitochondrial organelles. Of course, not having a mitochondrial organelle at all has biological implications that the organism must cope with. In the first place, how does Monocercomonoides sp. generate its energy? As stated above, MROs towards the most reduced end of the spectrum (e.g. mitosomes) have already lost the ability to produce ATP. Organisms with such organelles use other means instead, for example importing ATP from host cells in the case of intracellular parasites [8], or completely outsourcing the production ‘Textbook’ Mitochondrion Anaerobic Mitochondrion Hydrogenosome Mitosome ee- Loss of MRO in Monocercomonoides ee- O2 Not O2 ATP ISC ISC ATP ISC ISC ATP H2 Mitochondrial genome Generate ATP but oxygen is not the ternimal electron Oxidative phosphorylation to acceptor; other compounds generate ATP; oxygen is the are used, such as fumarate. terminal electron acceptor. Most reduced MRO; no No more detectable MRO electron transport; no oxidative phosphorylaNo oxidative phosphoryla- tion; no ATP generation; participate in Fe-S cluster tion, ATP is generated instead by substrate-level biosynthesis, localization phosphorylation; produce of the ISC pathway. hydrogen. Current Biology Figure 1. Mitochondrial reductive evolution. Very simplified view of mitochondria and related organelles. Major distinguishing features are shown (e.g., presence of a genome, electron transport chain, ATP production, ISC pathway), but by no means represent the full set of metabolic pathways (except for mitosome). Only discrete categories are shown, which do not represent the reality as many intermediate organelles have been described. The ISC pathway is the only function that exists throughout mitochondria and MRO diversity. of ATP to the cytoplasm by substratelevel phosphorylation in glycolytic reactions [3]. Monocercomonoides sp. apparently does just that, as deduced by the presence of a full glycolysis pathway as well as anaerobic fermentation enzymes [5]. Another implication of missing an MRO, in many ways more puzzling, is the absence of a mitochondrial Fe-S biosynthesis pathway (ISC). Fe-S clusters are cofactors of proteins that play essential roles in many cellular reactions, such as electron transport or enzyme catalysis. To be assembled properly in eukaryotes, Fe-S clusters require the joint action of the ISC pathway and its cytosolic counterpart, the CIA pathway [9]. This places the ISC pathway in a pivotal position for the proper functioning of cellular processes, and indeed has been regarded as the only unifying feature of mitochondria and MROs (Figure 1) [10]. So how does Monocercomonoides sp. assemble Fe-S clusters without an MRO? The answer, quite literally, comes from bacteria. Instead of the ISC pathway, Monocercomonoides sp. possesses bacterial genes encoding components of the sulfur mobilization (SUF) machinery, one of the prokaryotic systems that can assemble Fe-S clusters [11]. Acquired through lateral gene transfers (LGTs) from bacteria, these genes seemingly replaced the ISC system in Monocercomonoides sp., allowing it to fulfill the Fe-S biosynthesis requirements right from the cytosol. The precise timing of the SUF acquisition is unknown, but Karnkowska et al. propose that both the SUF and ISC systems have coexisted during some time [5]. This is a reasonable assumption because a relative species, Paratrimastix pyriformis, was found to have homologs of the same SUF system, most likely acquired in a common ancestor, although it remains to be seen whether P. pyriformis has also retained the ISC pathway. The hypothesized co-occurrence of the SUF and ISC systems in an ancestral lineage of Monocercomonoides sp. brings us to the heart of the issue. By creating redundancy, it is now possible to explain how Monocercomonoides sp. became completely amitochondriate. Specifically, the ISC pathway was no longer required since the SUF pathway can perform similar functions, making it dispensable and ultimately resulting in the complete loss of mitochondria. If correct, this scenario would reinforce our understanding of the minimal function of mitochondria, that is, in Fe-S cluster biosynthesis [10]. However, evolution generates diversity in infinite ways, and the mosaic of functions found in MROs is a prime example of that. Although still extremely rare, two other Current Biology 26, R408–R431, May 23, 2016 R411 Current Biology Dispatches cases of replacement of the ISC system are known in unrelated microbial lineages. These are Archamoebae and the breviate amoeba Pygsuia biforma, which have instead a bacterial nitrogenfixation (NIF) system and an archaeal SUF machinery, respectively [12,13]. In both cases, Fe-S requiring enzymes (e.g. [FeFe]-hydrogenase) have been retained along with the MROs where they function, in spite of the absence of the ISC system. Clearly, the situation is different in Monocercomonoides sp., which streamlined its mitochondrial function to the extreme — the loss of the organelle. So in such a complex array of organelles and functions, pinpointing an exact set of causes for mitochondrial loss is premature. It is likely that reductive mitochondrial evolution in Monocercomonoides sp. and MRO-containing lineages is not just the result of genetic opportunities (e.g. LGTs) and functional redundancy. Other forces are at play, including chance, biological constraints due to specific lifestyles (e.g. energy requirement), as well as varying responses to environmental conditions. More generally, such comparisons across the eukaryotic diversity vividly remind us, if need be, of the importance of discovery science. Our current understanding of eukaryote diversity and evolution (see [14] for a recent review) compels us to interpret the absence of mitochondrial organelles in Monocercomonoides sp. as a derived state. It would have been different 20 years ago, under the so-called Archezoa hypothesis, which postulated that some microbial eukaryote lineages diverged before the mitochondrial endosymbiosis, thus ancestrally lacking mitochondria [15]. If today we are confident in the secondarily amitochondriate nature of Monocercomonoides sp., it is because of the continuing discovery and functional characterization of a wide range of MROs in diverse lineages, as well as the improved resolution of the eukaryotic tree. The vast majority of eukaryotic diversity is composed of unicellular microbes — the protists — that, much like Monocercomonoides sp., are key to understanding the evolutionary paths that gave rise to this biodiversity. As shown here by Karnkowska and co-authors [5], genome sequencing is a powerful tool that can shed light on extraordinary cellular and evolutionary processes in unexplored parts of the biosphere. Current research has barely scratched the surface of protist diversity; it is now time to dig deeper. 7. Shiflett, A.M., and Johnson, P.J. (2010). Mitochondrion-related organelles in eukaryotic protists. Annu. Rev. Microbiol. 64, 409–429. REFERENCES 9. Stehling, O., and Lill, R. (2013). The role of mitochondria in cellular iron-sulfur protein biogenesis: mechanisms, connected processes, and diseases. Cold Spring Harb. Perspect. Biol. 5, a011312–2. 1. Poole, A.M., and Gribaldo, S. (2014). Eukaryotic origins: how and when was the mitochondrion acquired? Cold Spring Harb. Perspect. Biol. 6, a015990. 2. Pittis, A.A., and Gabaldón, T. (2016). Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry. Nature 531, 101–104. 3. Müller, M., Mentel, M., van Hellemond, J.J., Henze, K., Woehle, C., Gould, S.B., Yu, R.Y., van der Giezen, M., Tielens, A.G., and Martin, W.F. (2012). Biochemistry and evolution of anaerobic energy metabolism in eukaryotes. Microbiol. Mol. Biol. Rev. 76, 444–495. 4. Stairs, C.W., Leger, M.M., and Roger, A.J. (2015). Diversity and origins of anaerobic metabolism in mitochondria and related organelles. Phil. Trans. R. Soc. B 370, 20140326. 5. Karnkowska, A., Vacek, V., Zubacova, Z., Treitli, S., Petrzelkova, R., Eme, L., Novák, L., Zárský, V., Barlow, L.D., Herman, E.K., et al. (2016). A eukaryote without a mitochondrial organelle. Curr. Biol. 26, 1274–1284. 6. Timmis, J.N., Ayliffe, M.A., Huang, C.Y., and Martin, W.F. (2004). Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat. Rev. Genet. 5, 123–135. 8. Tsaousis, A.D., Kunji, E.R.S., Goldberg, A.V., Lucocq, J.M., Hirt, R.P., and Embley, T.M. (2008). A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453, 553–556. 10. Lill, R. (2009). Function and biogenesis of ironsulphur proteins. Nature 460, 831–838. 11. Takahashi, Y., and Tokumoto, U. (2002). A third bacterial system for the assembly of iron-sulfur clusters with homologs in archaea and plastids. J. Biol. Chem. 277, 28380– 28383. 12. van der Giezen, M., Cox, S., and Tovar, J. (2004). The iron-sulfur cluster assembly genes iscS and iscU of Entamoeba histolytica were acquired by horizontal gene transfer. BMC Evol. Biol. 4, 7. 13. Stairs, C.W., Eme, L., Brown, M.W., Mutsaers, C., Susko, E., Dellaire, G., Soanes, D.M., van der Giezen, M., and Roger, A.J. (2014). A SUF Fe-S cluster biogenesis system in the mitochondrion-related organelles of the anaerobic protist Pygsuia. Curr. Biol. 24, 1176– 1186. 14. Burki, F. (2014). The eukaryotic tree of life from a global phylogenomic perspective. Cold Spring Harb. Perspect. Biol. 6, a016147–7. 15. Cavalier-Smith, T. (1987). Eukaryotes with no mitochondria. Nature 326, 332–333. Imitation: Not in Our Genes Cecilia Heyes All Souls College and Department of Experimental Psychology, University of Oxford, Oxford OX1 4AL, UK Correspondence: cecilia.heyes@all-souls.ox.ac.uk http://dx.doi.org/10.1016/j.cub.2016.03.060 A powerful longitudinal study has failed to find any evidence that newborn babies can imitate facial gestures, hand movements or vocalisations. After 40 years of uncertainty, these findings indicate that humans learn to imitate; this capacity is not inborn. Humans are hyper-social animals. We depend on cooperation with others — relatives, friends, and strangers — to fulfil our basic needs, and to learn the R412 Current Biology 26, R408–R431, May 23, 2016 knowledge and skills that make human lives so very different from those of other animals. Since the 1970s [1], many scientists have been convinced