1638 Eukaryotic systematics: a user’s guide for cell biologists and parasitologists GISELLE WALKER1*, RICHARD G. DORRELL2†, ALEXANDER SCHLACHT3† and JOEL B. DACKS3* 1 Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK 2 Department of Biochemistry, University of Cambridge, Hopkins Building, Downing Site, Tennis Court Road, Cambridge, UK, CB2 1QW 3 Department of Cell Biology, School of Molecular and Systems Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7 (Received 12 November 2010; revised 22 November 2010; accepted 23 November 2010; first published online 15 February 2011) SUMMARY Single-celled parasites like Entamoeba, Trypanosoma, Phytophthora and Plasmodium wreak untold havoc on human habitat and health. Understanding the position of the various protistan pathogens in the larger context of eukaryotic diversity informs our study of how these parasites operate on a cellular level, as well as how they have evolved. Here, we review the literature that has brought our understanding of eukaryotic relationships from an idea of parasites as primitive cells to a crystallized view of diversity that encompasses 6 major divisions, or supergroups, of eukaryotes. We provide an updated taxonomic scheme (for 2011), based on extensive genomic, ultrastructural and phylogenetic evidence, with three differing levels of taxonomic detail for ease of referencing and accessibility (see supplementary material at Cambridge Journals On-line). Two of the most pressing issues in cellular evolution, the root of the eukaryotic tree and the evolution of photosynthesis in complex algae, are also discussed along with ideas about what the new generation of genome sequencing technologies may contribute to the field of eukaryotic systematics. We hope that, armed with this user’s guide, cell biologists and parasitologists will be encouraged about taking an increasingly evolutionary point of view in the battle against parasites representing real dangers to our livelihoods and lives. Keywords: Algae, primitive, phylogeny, parasite. INTRODUCTION development, as many diseases caused by protistan pathogens have their biggest impacts in Africa, To look around, the diversity of life would appear to South America and South-East Asia (see the World be populated by animals, plants and fungi. Health Organization webpage for the most recent and Appearances can be deceiving. Bacteria aside, the motivating statistics, http://www.who.int/vaccine_ vast diversity of cells on the planet today is composed research/diseases/en/). of unicellular eukaryotic microbes, or protists. These While the traditional approach to parasitology predominantly single-celled creatures can be at the involves focused experimental work in the individual same time beautiful, bizarre and deadly. Plasmodium organisms, a complementary way forward is to take a falciparum, the causative agent of cerebral malaria broader sweep, knitting together genetic, medical and which kills close to a million people a year (Snow et al. cell biological information across a framework of 2005), may be the most notorious protistan pathogen. eukaryotic relationships. This allows for comparisons It is hardly the only one. From our top (the brain- between distantly related parasites, yielding insight eating amoeba Naegleria fowleri) to our tail (gut into convergently evolved pathogenic mechanisms parasites Giardia and Entamoeba), a myriad array of (e.g. the regulations of antigenic variation in microbial eukaryotes – may inhabit, parasitise, and Plasmodium and Trypanosoma (Duraisingh et al. ravage the human body. Understanding the biology 2005; Horn and Barry, 2005)) or similarities that of these organisms and how they kill is a critical can be exploited in a single treatment (e.g. the use of task impacting not only human health but global metronidazole against anaerobic microbes). It also allows for comparisons between the parasites and * To whom correspondence should be addressed: Department of Cell Biology, School of Molecular and their free-living relatives. This can uncover the Systems Medicine, Faculty of Medicine and Dentistry, evolutionary path taken to parasitism and highlight University of Alberta, Edmonton, Alberta, Canada, T6 G lab-safe model organisms for study (e.g. the free- 2H7. Tel: +1-780-248-1493. Fax: +1-780-492-0450. living soil amoeba Naegleria gruberi instead of its E-mail: [email protected]. Department of Anatomy and deadly cousin Naegleria fowleri (Fritz-Laylin et al. Structural Biology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand. E-mails: [email protected]; 2010)). Finally, comparisons amongst parasitic [email protected]. sister-taxa allow for knowledge translation between † Contributed equally. experimental models and less studied related Parasitology (2011), 138, 1638–1663. © Cambridge University Press 2011 doi:10.1017/S0031182010001708 Downloaded from https:/www.cambridge.org/core. Open University Library, on 20 Jan 2017 at 08:23:37, subject to the Cambridge Core terms of use, available at https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0031182010001708 Eukaryotic systematics 1639 organisms. A result in Plasmodium might be appli- of gene sequences of mitochondrial origin (HSP60, cable to Eimeria:afinding in Trypanosoma brucei may HSP70, IscU) and later, the localizing of these gene be of relevance in Leishmania aetheopica. products (by immuno-microscopy) to double mem- This comparative approach means delving into brane-bound organelles found in these taxa (Clark fields initially appearing tangential to parasitology. and Roger, 1995; Bui et al. 1996; Roger et al. 1996, Our current understanding of eukaryotic systematics 1998; Tovar et al. 2003). Secondly, it has been shown is based both on molecular and microscopic evidence. that systematic phylogenetic error, such as ‘long Consequently molecular phylogenetics and genomics branch attraction’, has had a major effect on the are playing an increasingly important role. positioning of these organisms in the tree (Philippe Evolutionary cell biology and ancient eukaryotic and Germot, 2000; Dacks et al. 2002). The less evolution are two of the high-profile fields dependent conserved gene sequences were clustered together on eukaryotic systemics. They, in turn, are crucial for regardless of whether the divergence was due to rapid the interpretation of parasitological and cell biologi- evolution (as in many parasitic taxa) or a protracted cal data in this comparative framework. period of time in which to accumulate independent In this review, we will discuss the latest literature mutations (as in the prokaryotic sequences used as on higher-level protist systematics and provide an outgroups for the eukaryotic analyses). This artifact updated scheme of the major divisions of eukaryotic caused otherwise highly divergent protists to be diversity. Each of these divisions will be described, mistaken for basal eukaryotes. When accounted for, highlighting some of the parasitic organisms and the by algorithms and models that take different modes of current and upcoming genome projects. Finally, we sequence evolution into account (Holder and Lewis, will explore two of the most pressing controversies in 2003), the ‘primitive’ parasites and other proposed eukaryotic systematics and discuss the anticipated basal eukaryotes were either clearly linked with role that next generation sequencing might play in the relatives elsewhere in the tree (as in the case of evolutionary study of parasites and eukaryotes in Microsporidia and fungi (Keeling and Fast, 2002)) or general. were unresolved. The period following the demise of the Archezoa hypothesis was one of taxonomic agnosticism and SHIFTING VIEWS ON EUKARYOTIC SYSTEMATICS: caution with respect to interpretation of molecular FROM ‘ PRIMITIVE’ PROTOZOA TO DIVERSE sequence data and the evolution of eukaryotes. Such SUPERGROUPS data were still of immense value but a growing The tree of eukaryotes perhaps most familiar to many number of researchers abandoned the search for a parasitologists is that of a collection of crown single gene that would resolve relationships, great eukaryotes (animals, plants, fungi and many algae) and small, in favour of a strategy whereby different with a ladder-like sequential divergence of prominent genes were used to test hypotheses about particular parasites such as Giardia, Trichomonas, Encephalito- taxonomic relationships (e.g. EF2 demonstrating the zoon and Trypanosoma from the base. This view of monophyly of red and green algae (Moreira et al. eukaryotic relationships, and the place of parasites in 2000) or actin phylogenies uniting the cercozoans and it, was based on analyses of SSU rDNA genes and foraminiferans (Keeling, 2001)). These resolved single protein coding genes performed during the relationships would then contribute to a consensus early to mid-1990s (Sogin, 1991; Sogin and Silber- view of the eukaryotic tree as a whole. It was also a man, 1998). Such a phylogeny very much supported time for a renewed appreciation of ultrastructural the Archezoa hypothesis (Cavalier-Smith, 1983, data and the realization of the need for this to be 1987), a prevailing paradigm at the time (and still interpreted in the light of molecular results (Taylor, one sometimes held today) that these “amitochondri- 1999). ate” protists represent basal eukaryotic lineages that These ideas crystallized in a seminal paper by diverged before the acquisition of the mitochondrial