Protozoan paradigms for cell biology.

changing environments by modifying form and function to achieve homeostasis, and their vast diversity of cellular organisation provides an endless supply of novel material for biologists to investigate. Many of their oddities supply the exception that proves the rule. Among the most studied protozoa are parasites responsible for diseases of humans and other mammals, lower animals and higher plants. Such protozoa experience devastating changes of environment during the course of their often complex life cycles, whether they leave the host to face the outside world before infecting another host (as does Giardia that lives in the gut) or move directly from one host to another (as do vector-transmitted parasites such as the trypanosomes, leishmanias and malaria parasites). In addition, some must avoid elimination by host defences, innate or acquired. Not only has study of the cell biology of protozoan parasites told us much about parasitism as a way of life, it has also told us a great amount about cells in general. The kinetoplastid flagellates, which include the trypanosomes and leishmanias, have been pre-eminent in this respect. These organisms provided the first example of DNA in the cytoplasm: the kinetoplast, which is usually associated with the flagellar bases and is the structure that defines the group. In the early 1960s, the kinetoplast was revealed to be the massed DNA of the single mitochondrion that in Trypanosoma brucei undergoes cyclical repression (in the mammal) and activation (in the tsetse-fly vector), which enables the parasite to adapt to different energy sources and levels of oxygen availability. The kinetoplast is a polygenomic organelle that contains two types of DNA circle: maxicircles (which fulfil the role of mitochondrial DNA in other cells) and the more numerous minicircles (which hold the maxicircles together in a network whose replication products are readily segregated along with the flagellar basal bodies during cell division). The minicircles, it transpired, also encode guide RNAs that are crucial to the editing of faulty maxicircle transcripts. This ensures that the trypanosome can continue to switch its pattern of respiration in the vector and thereby survive transmission from a mammal to the insect vector. Dyskinetoplastic mutants that have suffered major maxicircle deletions cannot be transmitted. The kinetoplast/mitochondrion of trypanosomes has thus provided a splendid model for study of organelle continuity and of organelle activation and repression, as well as revealing for the first time the phenomenon of RNA editing (references in Hide et al., 1997). Cytoplasmic inheritance was pioneered by studies of freeliving ciliate protozoa, the investigations of Paramecium aurelia being most notable. This work raised the question of the relationship between bacterial symbionts and organelles in eukaryotes, and fuelled the massive explosion of interest in the endosymbiont theory of organellar origins. Studies of not only the mitochondria but also the choroplasts of protozoa such as the flagellate Euglena gracilis have contributed much to this debate. The cryptomonad flagellates, with their relict nucleomorphs, provide striking evidence for the evolution of a photosynthetic eukaryote symbiont into a plastid-like organelle. In recent years, the discovery of chloroplast remnants in the non-photosynthetic apicomplexan parasites Plasmodium and Toxoplasma has given cell biologists and parasitologists much food for thought (references in Coombs et al., 1998)! The question of whether all membrane-bound organelles are of symbiotic origin is not so easily answered, and protozoa provide a wealth of such organelles for study. Glycosomes, modified peroxisomes in kinetoplastids that contain enzymes of the glycolytic pathway and operate in conjunction with the mitochondrion in respiratory adaptation, provide a particularly puzzling case in point. The hydrogenosomes of anaerobic protozoa are clearly of polyphyletic origin, and most appear to be derived from mitochondria-like organelles that have surrendered all of their genes to the host nucleus (references in Coombs et al., 1998). The discovery of unusual organelles in parasites must always raise the question of whether these arose 2797 Journal of Cell Science 112, 2797-2798 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0674