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Transcript
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,
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© 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.
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© 2010 Macmillan Publishers Limited. All rights reserved