生物与其他生物之间有着永久的密切联系，其相互作用可以根据生物体的关联程度、这些相互作用的持续时间及其对双方的有益或有害影响来分类。所有的中间情况都存在，这形成了一个真正的连续体，其中既有需要其他生物体以养活自己的自由生物，也有生命周期完全受制于特定宿主的寄生虫。共生和寄生说明，除了极端多样化的情况外，相互作用在任何情况下对生物间的生活都至关重要，而且往往是由此构成的系统出现新特性的根源（are often at the origin of the emergence of new properties for the systems thus constituted）。例如，与每个生物体相关的微生物群正是如此。不过与健康个体相比，那些被寄生虫改变的生物体也是这种情况，寄生虫感染了它们，甚至扰乱受感染宿主的行为。
图1.共生与互惠的关系[资料来源：来自勒菲夫尔（Lefèvre）等人；见参考[2] （Coexistence physique durable(symbiose au sens large) 可持续的物理共存（广义上的共生）；Mutualisme(bebefice reciproque), avec ou sans coexistence 互惠主义（互惠互利），有无共存；Interaction parasite 寄生相互作用；Coexistence et mutualisme 共存与互惠；Interaction trasitoire 瞬态交互；Symbiose mutualiste: coexistence et benefice reciproque 互惠共生：共存互利）
图5. 人类微生物组多样性的代表 中间是代表微生物群落物种的系统发育树。在外围是特定微生物群的代表 （肠道、胃、口、阴道，等等）。[来源：从摩根（Morgan）等人复制的方案 (2013); 见参考文献[9].]（A map of diversity in the human microbiome 人类微生物组多样性图；Lactobacillus species (L.gasseri,L. jensenii.L.crispatus,L. iners) are predominant but mutually exclusive in the vagina 乳酸杆菌（Lactobacillus）属(格式乳杆菌（L. gasseri）,詹氏乳杆菌（ L. jensenii），卷曲亚种（L.crispatus）, 惰性乳杆菌（L.iners）)在阴道中占优势，但是相互排斥；Streptococcus dominates the oral cavity with S.mitis > 75% in the cheek 链球菌（Streptococcus）在口腔中占主导地位，脸颊上的缓症链球菌（S.mitis）>75%；Propionibacterium acnes lives on the skin and nose of most people 痤疮丙酸杆菌（Propionibacterium acnes）存在于大多数人的皮肤和鼻子上；Many Corynebacterium species characterize different body sites:C.matruchoti the plaque C.accolens the nose C. croppenstedtii the skin 许多棒状杆菌（Corynebacterium）是不同身体部位的特征：马氏棒杆菌（C.matruchoti）是牙菌斑的特征菌，拥挤棒杆菌（C.accolens）是鼻子的特征菌，克氏棒杆菌（C. croppenstedtii）是皮肤的特征菌；Several Prevotella species are present in the gastrointestinal tract. P. copri is present in 19% of the subjects and dominates the intestinal flora when present 胃肠道中存在着几种普雷沃氏菌（Prevotella）。19%的受试者中存在着粪源普雷沃氏菌（P. copri），并在存在时支配肠道菌；Bacteroides is the most abundant genus in the gut of almost all healthy subjects 在几乎所有的健康受试者的肠道中，拟杆菌（Bacteroides）是数量最多的一个属；Campylobacter includes opportunistic pathogens,but members live in the oral cavities of most Healthy people in the cohort 弯杆菌（Campylobacter）包括机会性病原体，但其成员生活在人群中大多数健康人的口腔中；E.coli is present in the gut of the majority of healthy subjects but at very low abundance 大肠杆菌（E.coli）存在于大多数健康受试者的肠道中，但含量非常低；Staphylococcus epidermidis colonizes external body sites 表皮葡萄球菌（Staphylococcus）定植于身体外部部位；Commensal microbes 共生微生物；Potential pathogens 潜在病原体；The four most abundant phyla 最丰富的四个门；Actinobacteria 放线菌门；Bacteroidetes 拟杆菌门；Firmicutes 厚壁菌门；Proteobacteria 变形菌门；Low abundance phyla 低丰度门；Chloroflexi 绿弯菌门；Spirochaetes 螺旋体门；Cyanobacteria 蓝细菌；Synergistetes 氧菌门；Euryarchaeota 广古菌门；Tenericutes 软壁菌门；Fusobacteria 梭杆菌门；Thermi 热硫杆状菌；Lentisphaerae 黏胶球形菌门；Verrucomicrobia 疣微杆菌门；Lactobacillus 乳酸杆菌；Streptococcus 链球菌；Corynebacterium 棒状杆菌属；Actinomyces 放线菌；Bifidobacterium 双歧杆菌属；Porphyromonas 卟啉菌属；Prevotella 普雷沃氏菌属；Bacteroides 拟杆菌属；Campylobacter 弯杆菌属；Neisseria 奈瑟氏菌属；Acinetobacter 不动杆菌属；Haemophilus 嗜血杆菌属；Escherichia 埃希氏菌属；Veillonella 韦荣氏球菌属；Selenomonas 月形单胞菌属；Fusobacterium 梭杆菌属；Anaerococcus 厌氧球菌属；Clostridium 梭菌属；Ruminococcus 瘤胃球菌属；Staphylococcus 葡萄球菌；Stool 粪便；Cheek 脸颊；Plaque 牙菌斑；Tongue 舌头；Nose 鼻子；Vagina 阴道；Skin 皮肤）
[1] Selosse M.A. (2000). La Symbiose. Vuibert, Paris.
[2] Lefèvre T., Renaud F., Selosse M.-A., Thomas F. (2010). Chapitre 14, Évolution des interactions entre espèces, in F. Thomas, T. Lefèvre & M. Raymond (ed.), Biologie évolutive, p. 555-653. De Boeck, Paris.
[3] Selosse MA, Gilbert A (2011) Des champignons qui dopent les plantes. La Recherche 457, 72-75.
[4] Selosse MA & Gilbert A (2011) Mushrooms that boost plants. Research 457, 72-75.
[5] Cleveland A., Verde E.A. & Lee R.W. (2011) Nutritional exchange in a tropical tripartite symbiosis: direct evidence for the transfer of nutrients from anemonefish to host anemone and zooxanthellae, Marine Biology, 158: 589-602
[8] Dawkins R. (1982) The extended phenotype. Oxford University Press, Oxford.
[9] Morgan X.C., Segata N. & Huttenhower C. (2013) Biodiversity and functional genomics in the human microbiome, Trends Genet. 29, 51–58
[10] Gross R., Vavre F., Heddi A.&Hurst G.D.D., Zchori-Fein E.&Bourtzis K.（2009）Immunity and symbiosis. Molecular Microbiology 3,751-759.
[11] Selosse M.A. （2016） Au delà de l’organisme: l’holobionte. Pour la Science,269,80-84.Combes C.（1995）Interactions durables. Écologie et évolution du parasitisme. Éditions Masson,525p.
[12] From Meeûs T. & Renaud F（2002）Parasites within the new phylogeny of eukaryotes. Trends in Parasitology 18, 247-251.
[13] De Meeûs T., Prugnolle F. & Agnew P. (2009) Asexual reproduction in infectious diseases. In Lost Sex, Schön I, Martens K & van Dijk P eds, Springer, NY, p. 517-533.
[17] Zheng et al (2011) Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biology 12: R116
[18] Dawkins R. (1976) The selfish gene. Oxford University Press.
[19] Lefèvre T.&Thomas F（2008）Behind the scene, something else is pulling the strings: Emphasizing parasitic manipulation in vector-borne diseases. Infection, Genetics and Evolution 8,504-519.
Jacques JOYARD, 乔亚德·雅克，法国国家科学研究中心（CNRS），格勒诺布尔大学，细胞与植物生理学实验室主任级研究员。
Symbiosis and parasitism
Living organisms are permanently closely associated with each other. Their interactions can be classified according to the level of association of the organisms involved, the duration of these interactions and their beneficial (or not) impact on both partners. All intermediate situations exist, forming a true continuum from free organisms that need other organisms to feed themselves to parasites which life cycle is entirely based on specific hosts. Symbiosis and parasitism illustrate -beyond the extreme diversity of situations- that interactions are in all cases essential to partners’ lives, and are often at the origin of the emergence of new properties for the systems thus constituted. This is the case, for example, of microbiota associated with each of the living organisms. But it is also the case for organisms modified by parasites that infect them and even disturb the behaviour of infected hosts compared to healthy individuals.
The network of interactions and interdependencies that exists between billions of organisms within the biosphereA living space where all the Earth’s ecosystems are located, corresponding to the thin layer of the atmosphere, hydrosphere and lithosphere where life is present. This dynamic living space is maintained by an energy supply (mainly due to the sun) and the metabolism of living organisms in interaction with their environment.; a level of organization that is founder of the concept of biodiversity (read What is biodiversity?). These interactions are most often of mutual benefit and their role in the physiology and adaptation of organisms to the environment is essential. For example, many animals cannot digest without the help of bacteria in their digestive tract, most plants can only use the soil with fungi colonizing their roots, which they feed in return [1].
Figure 1. Relationship between symbiosis and mutualism. [Source: From Lefèvre et al.; see ref. [2].
But this is not always the case: interactions between two organisms can be classified according to their beneficial, harmful or neutral effect for both partners. Thus, one can distinguish interactions that are beneficial for one partner and harmful for the other (predation, parasitism), beneficial for one and neutral for the other (commensalism) and mutually beneficial interactions (mutualism). In addition, all intermediate situations exist, in a true continuum of interaction types (Figure 1) [2]. They can also be classified according to their instantaneous (predation) or sustainable nature (parasitism, mutualism, etc.), as well as according to the degree of association between the partners [2]. Etymologically, the term symbiosis refers to “the common life of organisms of distinct species”. This broad definition refers to a sustainable coexistence, involving all or part of the life cycle of the two organisms, regardless of the exchanges between them. A more restrictive definition reserves the term symbiosis for sustainable and mutualist coexistence (see red part in Figure 1).
Other benefits depend on the ability of one of the partners to move (pollination by bees, seed dispersal by ants or birds). On the balance sheet, similarly functioning associations have been set up several times during the evolution. Such convergences are illustrated by the diversity of insects cultivating fungi (ants, termites, beetles) and eukaryotesUnicellular or multicellular organisms whose cells have a nucleus and organelles (endoplasmic reticulum, Golgi apparatus, various plasters, mitochondria, etc.) delimited by membranes. Eukaryotes are, together with bacteria and archaea, one of the three groups of living organisms. that harbour photosynthetic algae in their cells (such as the appearance of chloroplastsOrganites of the cytoplasm of photosynthetic eukaryotic cells (plants, algae). As a site of photosynthesis, chloroplasts produce O2 oxygen and play an essential role in the carbon cycle: they use light energy to fix CO2 and synthesize organic matter. They are thus responsible for the autotrophy of plants. Chloroplasts are the result of the endosymbiosis of a photosynthetic prokaryote (cyanobacterium type) in a eukaryotic cell, about 1.5 billion years ago. in the eukaryotic cell) (see Symbiosis and evolution). All the organizations have had the opportunity to contract, during their evolution, one or more mutualist symbiosis(s). This is particularly true for large multicellular organisms, which constitute an ecosystem for microscopic organisms. The rhizosphere (the soil surrounding the root of plants) or the digestive tract of animals are thus major microbial niches, populated by thousands of species for each individual host, some of whose occupants are favourable to the host. As a result, each organism has a procession of symbiotes, especially developed in multicellular organisms.
Other emergences are functional. In the example of nodules (Figure 4D), the bacteroid uses energy obtained from its respiration to reduce -thanks to the nitrogenaseEnzyme complex specific to certain prokaryotes that catalyzes the complete sequence of reactions during which the reduction of dinitrogen N2 leads to the formation of ammonia NH3. This reaction is accompanied by hydrogenation.– the atmospheric nitrogen N2 to ammonium NH3, which serves as a source of nitrogen for the plant (and bacteroid). Conversely, the plant provides carbon and oxygen supply. Oxygen is required for respiration, but nitrogenase is inactivated by oxygen: this contradiction explains why a free rhizobiumAerobic soil bacterium that can create symbiosis with legumes. These bacteria are found in nodules where they will fix and reduce atmospheric nitrogen, which can then be assimilated by the plant. In exchange plants provide carbonaceous substrates to bacteria. in the soil is unable to fix nitrogen. On the other hand, in the nodosity, oxygen does not diffuse freely, but is captured by a protein of the host cell, leghaemoglobin [7]. Located around the bacteroid, leghaemoglobin protects the nitrogenase from the inactivating effects of the oxygen and provides an oxygen reserve for bacteria respiration. Nitrogen fixation can therefore only be achieved within in the nodosity.
Many other functional traits are induced by symbiosis, such as some protective effects that rely on the induction of partner defences, tolerated by the symbiont but harmful to pathogens. Mycorrhizal fungi, for example, induce the accumulation of protective tannins at the root level, which are responsible for inducing an increased level of defence and reactivity throughout the plant, including the aerial parts. Thus, the mycorrhized plant reacts faster and more strongly to an herbivore or parasite than a non-mycorrhized control plant. In lichens, algae induce the fungus to synthesize secondary metabolites that have a protective role against strong light and herbivores.
Figure 5. Representation of the diversity of the human microbiome. In the centre is the phylogenetic tree representing the species of the microbiota. On the periphery, representation of specific microbiota (gut, stomach, mouth, vagina, etc.). [Source: Scheme reproduced from Morgan et al (2013); See ref. [9].]Overall, the phenotypeAll the observable characteristics of an individual. of the organism therefore also results from its symbionts, either by adding their capacities or because they modify it. The phenotype is therefore more than what the genome encodes. Symbionts and their genes are part of what Dawkins [8] calls an “extended phenotype”, that is, the set of elements recruited into the environment that modify the phenotype of a species. In humans, for example, the digestive tract contains a large number of bacterial species (Figure 5): metagenomic analysis applied to our intestine has shown that it contains nearly 100,000 billion microorganisms, ten times more than our own cells! This is called the microbiota (see Human microbiotas: allies for our health).
The gut microbiotaAll microorganisms (bacteria, yeasts, fungi, viruses) living in a specific environment (called microbiome) in a host (animal or plant). An important example is the set of microorganisms living in the intestine or intestinal microbiota, formerly called “intestinal flora”. is essential for the proper functioning of its human host, not only in terms of digestion or vitamin production, of course, but also for metabolism, immunity… or the nervous system. The imbalances in the intestinal flora are now suspected of being at the origin of a series of pathologies: obesity, diabetes, cardiovascular diseases, allergies, inflammatory diseases, even autism [2],[7]. The human microbiota is not limited to the digestive tract: international metagenomic programs have identified genes from a large number of symbiotic microorganisms living in the mouth, nose, vagina or on the skin (Figure 5).
Figure 6. Microbial modulation of interactions between a host and its parasites/pathogens. The action of the host genotype (represented by the blue ellipse) and all environmental factors that affect the composition of the microbiota will affect the interaction between the host and its parasites/pathogens, particularly through the immune system. [Source: Adapted from Gross et al. [See ref. 10]]The microbiota is able to modulate the interactions between a host and its parasites/pathogens (Figure 6). The action of the microbiota can be direct (competition) or indirect through its action on the establishment, maturation and functioning of the immune system. We know, by studying mice raised in an axenicCaracterise a culture (of prokaryotic or eukaryotic cells, tissues, living organisms) free of all saprophytic or pathogenic germs. environment, that the development of the nervous system and even the behaviour are partly influenced by it!
It has therefore been proposed that the unit relevant for biology or evolution should be less the organism than the symbiotic procession: we speak of holobiontemeans the biological unit composed of the host (plant or animal) and all its microorganisms. to name this entity more relevant to the importance of biotic interactions [11].
4. Parasitism, an evolutionary success story
If one of the partners in the symbiosis discovers how to use the other effectively, it becomes a parasite. There is indeed a continuum between symbiosis and parasitism [5]. The parasite exploits resources provided by another unrelated individual, the host, to the detriment of the latter. Parasitism is a long-lasting interaction with a host, unlike predation, where the interaction lasts only as long as the time of capture and digestion. However, from an evolutionary point of view, it can be said that predation is only an extreme form of parasitism. There are parasites that slowly kill their host. This is the case of plant parasitic fungi (Mildew, Armillaries, Hoof fungus, etc…) that complete their life cycle on dead tissues. When a cheetah grabs an antelope, there is an exchange of energy and only energy. In host parasite systems where the host survives (referred to as biotrophic parasitism), the duration of the interaction is quite different: the two organisms then live together, often one in the other, sometimes cell in cell or even genome within genome. The genetic information of each partner is expressed side by side and durably in a tiny portion of space [11].
All living beings are affected by parasitism as hosts or parasites (Figure 7). Among the known species, 30% of the approximately 2 million eukaryotic species are thought to be parasites [12]. The best known parasito-faunaAll the parasitic fauna of an organism. is that of man. It consists of 179 species of parasites, 35 of which appear to be specific to Homo sapiens [13]. This image can be increased by hyperparasitism (parasite’s parasites), a widespread phenomenon in parasitic arthropods and parasitoidsAn organism that develops on or in a “host” organism in a two-phase process: it is first biotrophic and then predatory, leading to the final death of the host. [14]. Recent estimates suggest that the world of viruses, which parasitize cells by diverting their functioning to the production of new viral particles, has been profoundly underestimated. They are present in all ecosystems and would constitute the most abundant and diversified genetic entities in living organisms [15].
For evolutionistsPartisans of evolutionism, who believe that species evolve over time,, host-parasite models raise countless questions about parasitism itself, the evolutionary dynamics of their interactions, and the evolutionary consequences on host species. The role played by parasites on the world of free species is indeed enormous. The success of the parasitic lifestyle has never been denied throughout the evolutionary process because a host offers, to any organism that knows how to exploit it, not only habitat and food but also an effective means of dispersal. While in the past, research has focused on the direct effects of pathogens on the fertility and survival of their hosts, current research illustrates consequences on such diverse traits as behaviour, selection processes and life history, to name but a few.
The parasite cycle is the result of the transformations undergone by a parasite during its lifetime to ensure its reproduction, in the various ecological niches it occupies: host(s), external environment. While many parasite species have simple cycles, exploiting a single host species, others successively exploit several host species: this allows seasonal relays, or to multiply infectious forms, because the success rate of host colonization is often low. The complexity of the cycles has appeared several times independently during the evolution. Among the most complex records, we can mention the case of the trematode Halipegus ovocaudatus whose cycle includes 4 obligatory hosts: a mollusc, a crustacean copepod, a dragonfly larva and a frog. In addition to these extreme situations, complex cycles with two or three hosts are found, particularly in helminthsGeneric term that includes various types of worms that are generally parasitic: roundworms (nematodes), thorny trunk worms (acanthocephalus – “thorny-headed” worms) and flatworms (plathelminths : these are codes and trematodes). or rust (pathogenic fungi). In addition to the complexity of simple cycles, there are also complex cycles during the evolution of secondary simplifications.
When infected with plasmodium, mosquitoes change their behaviour: they become more active, more aggressive and bite more people, thus increasing their probability of transmission [2]. These changes seem to be synchronized with the development of the parasite (e.g. decrease in mosquito bite rate when the parasite is immature, and increase when the parasite has reached the transmissible stage). Once in the vertebrate host, these same parasites seem to be able to modify the odours of the hosts to make them more attractive to mosquito vectors. This change in host behaviour after infection is a characteristic example of parasitic manipulation [2].
6. Parasitic manipulations
Some parasites are capable of significantly modifying the physiology, morphology or behaviour of their host with the consequence of increasing their probability of transmission. This host exploitation strategy is now described in many host parasite systems phylogeneticallyAdverb describing the result of an analysis of the relationship relationships between distant living things. distant. Phenotypic Characterize a trait or character of a living organism (anatomical, physiological, molecular or behavioural aspects), which can be analyzed. changes in infected hosts are generally considered an illustration of the extended phenotype concept [18]. These phenotypic changes actually correspond to the expression of the parasite’s genes and the effect of the corresponding proteins on the host’s phenotype. According to this idea, these induced modifications are adaptive for the parasite and not for the host.
Some parasite manipulations lead the host to suicidal behaviour. A well described case is that of non-segmented nematomorphsWorms with cylindrical bodies, extremely long and thin (on average from 0.5 to 2.5 mm in diameter for 10 to 70 cm in length). Also called Gordian worms because of the impression they give of making complicated knots with their bodies. worms, whose adult form lives in water and looks like a kind of thread. The host is usually a terrestrial insect, such as a grasshopper (Figure 7H) that hosts the larval form. The adult worm must return to the aquatic environment to reproduce. To do this, it manipulates the host’s behaviour, forcing it to jump into the water. Thanks to this final drowning, he can then return to the environment in which he completes his life cycle. However, this type of suicidal can be beneficial to noninfected animals of the same species, as it reduces the risk of contamination. This is the case of the ant parasitized by Ophiocordyceps (Figure 9B), which is then recognized as such and rejected from the anthill by its congeners.
In a few cases concerning plants, the determinism of handling is a little better known. It reveals a surprisingly convergent mechanism in pathogenic fungi and bacteria, but also in plant-parasitic nematodesRound, non-segmented worms. Some lead a “free” life (in soil, water, etc.). Others have a parasitic life, within fungal, plant or animal organisms.. They cause root deformations where they take shelter and feed, called galls. The genomes of these organisms encode a multitude of small secreted proteins (or peptides), which modify the functioning of other host proteins. We talk about effectors: some penetrate the host cells, and reorganize the metabolism or alter the defense reactions… Sometimes they act at the level of the cell nucleus and are responsible for changes in gene expression. It is likely that these mechanisms also play a role in other types of parasitism: they are even found in mycorrhizal fungi. This suggests that secreted peptides could contribute to the changes observed in mutualist symbiosis – again highlighting the existence of similarities in mechanisms between mutualist and parasitic symbiosis.
Beyond the spectacular and fascinating nature of parasitic manipulation, some of the pathogens involved are responsible for many crop losses, but also for serious diseases, including vector-borne diseases such as malaria mentioned above, dengueMosquito-borne viral infection in tropical and subtropical regions around the world. Causes a flu-like syndrome that can progress to life-threatening complications. There is no specific treatment for dengue fever,, trypanosomiasisInfections caused by trypanosome parasites, or leishmaniasisParasitic diseases causing very disabling or even fatal skin or visceral diseases if not treated. They are caused by various parasites of the genus Leishmania, transmitted by the bite of insects commonly known as sandflies., and thus represent major public health problems [19].
[1] Selosse M.A. (2000). La Symbiose. Vuibert, Paris.
[2] Lefèvre T., Renaud F., Selosse M.-A., Thomas F. (2010). Chapitre 14, Évolution des interactions entre espèces, in F. Thomas, T. Lefèvre & M. Raymond (ed.), Biologie évolutive, p. 555-653. De Boeck, Paris.
[3] Selosse MA, Gilbert A (2011) Des champignons qui dopent les plantes. La Recherche 457, 72-75.
[4] Selosse MA & Gilbert A (2011) Mushrooms that boost plants. Research 457, 72-75.
[5] Cleveland A., Verde E.A. & Lee R.W. (2011) Nutritional exchange in a tropical tripartite symbiosis: direct evidence for the transfer of nutrients from anemonefish to host anemone and zooxanthellae, Marine Biology, 158: 589-602
[7] Leghaemoglobin. Oxygen binding protein with a structure very similar to blood hemoglobin. Present in the nodules of legumes, it protects the enzymatic complex (nitrogenase/hydrogenase) from the effects of oxygen which inactivates it and constitutes a reserve of oxygen for bacteria (aerobic activity).
[8] Dawkins R. (1982) The extended phenotype. Oxford University Press, Oxford.
[9] Morgan X.C., Segata N. & Huttenhower C. (2013) Biodiversity and functional genomics in the human microbiome, Trends Genet. 29, 51–58
[10] Gross R., Vavre F., Heddi A. & Hurst G.D.D., Zchori-Fein E. &Bourtzis K. (2009) Immunity and symbiosis. Molecular Microbiology 3, 751-759.
[11] Selosse M.A. (2016) Au delà de l’organisme : l’holobionte. Pour la Science, 269, 80-84.
[11] Combes C. (1995) Interactions durables. Écologie et évolution du parasitisme. Éditions Masson, 525 p.
[12] From Meeûs T. & Renaud F. (2002) Parasites within the new phylogeny of eukaryotes. Trends in Parasitology 18, 247-251.
[13] De Meeûs T., Prugnolle F. & Agnew P. (2009) Asexual reproduction in infectious diseases. In Lost Sex, Schön I, Martens K & van Dijk P eds, Springer, NY, p. 517-533.
[14] Parasitoid: an organism that develops on or in a “host” organism in a two-phase process: it is first biotrophic and then predatory, leading to the final death of the host.
[15] Hamilton G. (2008) Welcome to the virosphere. New Scientist 199, 38-41.
[17] Zheng et al (2011) Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biology 12: R116
[18] Dawkins R. (1976) The selfish gene. Oxford University Press.
[19] Lefèvre T. & Thomas F. (2008) Behind the scene, something else is pulling the strings: Emphasizing parasitic manipulation in vector-borne diseases. Infection, Genetics and Evolution 8, 504-519.
