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NEWS & VIEWS MAL ARIA The gorilla connection Plasmodium falciparum is the agent of the deadliest form of human malaria. A survey of Plasmodium diversity in African apes reveals that western gorillas are the reservoir species for this parasite. S A . E D WA R D C . H O L M E S W hen it comes to disease, chimpanzees get a bad press. We have known for more than a decade that chimpanzees are the source of HIV-1, the major cause of AIDS, and probably acquired the virus themselves by eating infected monkeys1. More recently, chimpanzees have been proposed as the reservoir of human Plasmodium falciparum2, a parasite that causes the most severe type of malaria. On page 420 of this issue3, however, Liu et al. show that another of our great-ape cousins — the gorilla — is in fact a more likely progenitor species for this form of human malaria. Common chimpanzees (Pan troglodytes) carry their own type of malaria parasite, Plasmodium reichenowi. For some time, this was represented by a single isolate, which seemed to be the closest relative of human P. falciparum. Such an intimate phylogenetic relationship quite reasonably led to the idea that these two Plasmodium species diverged at the same time as humans and chimpanzees separated, between 5 million and 7 million years ago4. This theory of host–parasite co-divergence was accepted with little challenge until recent studies revealed that African primates carry a far greater diversity of Plasmodium than previously realized2,5,6, leading to a re-evaluation of the likely ancestry of human malaria. Of most note, it has been proposed that the genetically homogeneous P. falciparum of humans is simply a strain of the more diverse P. reichenowi that jumped from chimpanzees, and far more recently than implied by co-divergence2. Liu et al.3 made their discovery through two key extensions to the sampling of Plasmodium biodiversity in non-human primates. First, by using ape faecal material, obtained noninvasively, as a source of Plasmodium DNA, they were able to examine more than 2,500 retrospectively collected samples from chimpanzees, bonobos (Pan paniscus) and both eastern gorillas (Gorilla beringei) and western gorillas (Gorilla gorilla) from central Africa. Second, they employed a genome-amplification technique that enabled them to screen for animals that had been infected with multiple Plasmodium lineages. The results of their survey are striking: Human P. falciparum C1 G1 C3 G3 C2 G2 Other Plasmodium species Figure 1 | Origin of human Plasmodium falciparum. This phylogenetic tree illustrates the remarkable diversity of Plasmodium parasites infecting African apes, as documented by Liu et al.3, and their relationship to human P. falciparum. The tree describes evolutionary patterns in Plasmodium strains isolated from chimpanzees (groups C1–C3; blue) and western gorillas (groups G1–G3; red) in central Africa. The original strain of chimpanzee Plasmodium reichenowi falls into group C1. The genetically homogeneous human P. falciparum strains (black) fall within the diversity of gorilla parasites in group G1, suggesting that their ancestry lies with gorillas. The point of cross-species transmission from gorillas to humans is marked by an arrow, but its timing is uncertain. whereas no Plasmodium infection was evident in either bonobos or eastern gorillas, 32–48% of the chimpanzee and western gorilla individuals sampled carried Plasmodium parasites, with mixed infection being commonplace. In addition, the Plasmodium lineages found in western gorillas were clearly the closest relatives of human P. falciparum, strongly suggesting that this parasite jumped into humans from western gorillas, not chimpanzees, and that this cross-species transmission event occurred just once (Fig. 1). Studies of pathogen biodiversity are in vogue, and are often set within the idea that they will allow the next human pandemic to be predicted, and hence prevented7. It is probably simplistic to think that describing what is out there in nature will permit disease emergence to be forecast with any accuracy, particularly because successful emergence also depends on aspects of pathogen genetics and epidemiology. But field studies of pathogen biodiversity undoubtedly provide a valuable genetic catalogue that will greatly assist efforts to understand the origins of human disease. Although the screen of Plasmodium biodiversity undertaken by Liu et al.3 is by far the largest of its kind, 4 0 4 | NAT U R E | VO L 4 6 7 | 2 3 S E P T E M B E R 2 0 1 0 © 2010 Macmillan Publishers Limited. All rights reserved it seems certain that more intensive samplings of non-human primates will uncover even more diverse lineages of the malaria parasite, some of which may have the potential to emerge in humans. Enhanced sampling will also help to determine whether the apparent absence of Plasmodium in eastern gorillas and bonobos is because it has never infected these species, or has become extinct in them, or because it is simply at very low prevalence. The study of Liu et al. sheds new light on the origins of malaria, but it unfortunately complicates our understanding of the timescale over which this emergence event took place. The beauty of the idea that P. reichenowi and P. falciparum co-diverged with their primate hosts was that it provided a ready-made timeframe for the evolutionary history of malaria. If these two parasites diverged with their hosts between 5 million and 7 million years ago, then estimating the time span of the remainder of the Plasmodium family tree, or of more recent diversification within human P. falciparum, becomes a relatively straightforward scaling exercise. However, no such simple calibrations are possible with cross-species transmission, and NEWS & VIEWS RESEARCH 1. Bailes, E. et al. Science 300, 1713 (2003). 2. Rich, S. M. et al. Proc. Natl Acad. Sci. USA 106, 14902–14907 (2009). 3. Liu, W. et al. Nature 467, 420–424 (2010). 4. Rich, S. M., Licht, M. C., Hudson, R. R. & Ayala, F. J. Proc. Natl Acad. Sci. USA 95, 4425–4430 (1998). 5. Ollomo, B. et al. PLoS Pathog. 5, e1000446 (2009). 6. Prugnolle, F. et al. Proc. Natl Acad. Sci. USA 107, 1458–1463 (2010). 7. Pike, B. L. et al. Clin. Infect. Dis. 50, 1636–1640 (2010). 8. Drummond, A. J., Pybus, O. G., Rambaut, A., Forsberg, R. & Rodrigo, A. G. Trends Ecol. Evol. 18, 481–488 (2003). 9. Linz, B. et al. Nature 445, 915–918 (2007). More giants in focus A fresh analysis of data from gravitational microlensing surveys for planets orbiting stars other than the Sun finds that gas-giant planets similar to Jupiter are more common than previously thought. T he Sun’s planetary configuration seems ideally suited to the emergence of advanced life. Small, rocky planets lie in the pleasantly warm region close to the Sun. The giant, gas-rich planets orbit far enough away to avoid disturbing the rocky planets, while their gravitational perturbations help scatter incoming comets that represent a collision hazard. Is the Solar System typical or is this arrangement unusual, perhaps even unique? Writing in The Astrophysical Journal, Gould et al.1 present an analysis of extrasolar planetary discoveries that brings us a step closer to answering this question. So far, most extrasolar planets have been found by one of two methods. The Doppler velocity technique measures small shifts in the radial velocity of a star caused by the gravitational tug of an orbiting planet. The transit technique detects periodic decreases in a star’s brightness when a planet passes in front of it. Both methods yield a population biased towards massive planets orbiting close to their star. Analysis of data from a large Doppler velocity survey 2 suggests that about 10% of solar-mass stars possess a planet at least as massive as Saturn, orbiting within 3 astronomical units (au) of the star (1 au is the average distance from Earth to the Sun). Gould et al.1 analysed data obtained using a different technique, microlensing. Here, a relatively faint star passing in front of a distant bright star acts as a gravitational lens, focusing light from the distant object, magnifying it and causing it to brighten and fade with a characteristic ‘light curve’ over a period of weeks (Fig. 1a). If the nearer star possesses a planet, it too acts as a lens, altering the light curve accordingly (Fig. 1b). This alteration can be large, even for a low-mass planet, but the deviation lasts for only a matter of hours, so finding and characterizing a planet requires continual monitoring of an ongoing microlensing event. Resources are limited, so many events are observed only sporadically, biasing the distribution of planets that are found as a result. Gould and colleagues argue that rare, veryhigh-magnification events receive sufficient attention to provide an essentially unbiased sample. Out of 13 such events between 2005 and 2008, five resulted in planetary detections, including one two-planet system — yielding six planets in all. Using these data, the authors have estimated the abundance of planets as a function of mass and orbital separation from the host star. The small sample size means that the numbers may change somewhat in light of future discoveries. However, two conclusions seem to be robust. The first is that many more stars have Time Observer Observer E X T RASOL AR PL ANETS JOHN CHAMBERS Brightness Edward C. Holmes is at the Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA, and the Fogarty International Center, National Institutes of Health, Bethesda, Maryland. e-mail: [email protected] Brightness so the timescale of malaria’s origin is now shrouded in mystery. For rapidly evolving RNA viruses such as HIV-1, it is possible to calibrate the ‘molecular clock’ and estimate divergence times simply by counting the number of mutations between isolates sampled at different times8. However, this approach is inappropriate for organisms such as Plasmodium, in which rates of evolutionary change are far lower. The only remaining option is to use some other external calibration point to set the tick rate of the molecular clock, perhaps invoking ancient geological events such as continental drift, or more recent evolutionary phenomena such as the movement of archaic human populations out of Africa9. Understandably, however, these assumptions can prove contentious. Resolving the timescale of malaria’s origin provides added impetus for the more widespread sampling of Plasmodium genetic diversity in a diverse array of mammalian species. O Time Figure 1 | Detecting planets by microlensing. a, When a faint star (red) passes in front of a more distant bright star (yellow), it focuses light from the distant object, causing it to brighten and fade over several weeks with a characteristic ‘light curve’. b, The presence of a planet (brown) orbiting the nearer star causes additional brightness variations on a timescale of hours. Continual monitoring of a microlensing event can determine whether planets are present, and yields their mass and orbital separation from the parent star. Gould et al.1 found that out of 13 such events, 5 resulted in planetary detections. giant planets than was previously believed. Microlensing is sensitive to planets that lie at a particular separation from a star when projected on the sky. This separation is about 2.5 au for typical lensing stars that have masses roughly half that of the Sun. Planets that lie far from this separation, especially low-mass planets, will not be seen. Despite this limitation, more than a third of the stars in the sample of Gould et al.1 have planets, a fraction that is likely to be an underestimate, yet one that is already several times larger than the fraction found by Doppler velocity surveys2. Five of the six microlensing planets have masses between 50 and 300 times that of Earth. These objects are likely to be ‘gas giants’ similar to Jupiter and Saturn, consisting of a massive hydrogen–helium-rich envelope surrounding a small solid core. Theorists have long predicted3 that gas giants form in the cool, outer regions of a young star’s protoplanetary disk, beyond the ‘snow line’ — the distance at which water ice begins to condense. For solar-mass stars, the snow line probably lies several astronomical units from the star4, which means that almost all the planets found by the Doppler velocity and transit techniques actually lie inside — not outside — the snow line. 2 3 S E P T E M B E R 2 0 1 0 | VO L 4 6 7 | NAT U R E | 4 0 5 © 2010 Macmillan Publishers Limited. All rights reserved