Parasites Shed Light on Cellular Evolution
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Mon Jul 31 18:52:38 EST 2000
I have '97' PDF article RCJ
Cell Biology: Parasites Shed Light on Cellular Evolution
By now, it's well established that the cells of higher organisms acquired some
of their most important components--the energy-producing mitochondrion and the
photosynthesizing chloroplast--when they engulfed much simpler bacterial cells,
which then took up residence and now provide those key services. But now, it
seems that even a complex cell can be engulfed by another cell and become an
essential part of it.
The alga inside. The parasite Toxoplasma and its relatives may have derived an
organelle with multiple membranes (arrow, right) from an ingested alga.
Source: Köhler et al.; Illustration: K. Sutliff
On page 1485, molecular parasitologists Sabine Köhler and David Roos of the
University of Pennsylvania, molecular evolutionist Jeff Palmer, and botanist
Charles Delwiche of Indiana University and their colleagues report that the
chloroplast-like organelles recently found in an important group of
single-celled parasites apparently arose when one of the parasites' ancestors
engulfed, and then retained, a chloroplast-containing algal cell. The work adds
to the growing evidence suggesting that secondary endosymbiosis, as it is
called, may have been a relatively common event in evolution: There is already
strong evidence that it occurred in some of the commonest types of algae,
perhaps on several different occasions.
While no one yet knows exactly what function the plastids have in the parasite
group--which includes Toxoplasma, a common cause of infections in AIDS
patients, and the malaria-causing Plasmodium--the fact that they have been
retained through evolutionary history suggests that they are essential. That
would make them tempting targets for drug therapies, because humans and other
mammalian hosts of the parasites don't have such organelles. Indeed, says
molecular parasitologist Jean Feagin of the Seattle Biomedical Research Center,
researchers are attracted "almost like flies to the potential that this could
The first clue that the parasites carry plastids came when researchers found
that Plasmodium and its relatives carry three distinct sets of genetic
material: the usual nuclear DNA, a small circular molecule, and an even shorter
linear fragment. Scientists at first thought the circular piece belonged to the
cells' mitochondria, which typically have circular remnants of the original
bacterial genome. But on closer examination, they found that the circular DNA's
sequence contained some key features of the plastid DNA of plants and algae,
while the linear piece turned out to be the mitochondrial DNA. That was very
puzzling, says Roos. "Here, we have a genome without a known function and
without a known home [in the cell]," he says.
Last year, while studying Toxoplasma, botanist Geoffrey McFadden of the
University of Melbourne in Australia and his colleagues provided the first
solid evidence for the misfit genome's home. They selectively tagged the
plastidlike DNA and found that it indeed resides in a small membrane-bound
organelle that had no obvious function. That finding only deepened the puzzle,
says Roos: "Its DNA looks more like a chloroplast's than a mitochondrion's, but
these are not plants. So, what are they doing with a chloroplast?"
The current work, says McFadden, "provides that missing piece of the puzzle."
The team presents two lines of evidence that the parasites obtained their
plastid when one of their ancestors attempted to eat a chloroplast-containing
algal cell. First, electron-microscope images revealed that the Toxoplasma
organelle is surrounded not just by two membranes, as chloroplasts and
mitochondria normally are, but by four. The inner two, the researchers reason,
are from the double-membraned plastid that existed inside the engulfed cell.
The third derives from the outer membrane of the algal cell, while the
outermost membrane came from the vacuole formed when the host cell surrounded
and engulfed the potential prey. Second, a phylogenetic analysis of one of the
plastid genes suggested that it is more closely related to a gene in the
plastids of green algae than to the comparable gene in the photosynthetic
bacteria that were the original source of chloroplasts.
The scientists acknowledge that neither line of evidence is strong enough to
stand alone. "I wouldn't bet my life on there being four membranes there," says
Roos, who notes that it is sometimes difficult to see all four clearly. And
Palmer, whose laboratory conducted the phylogenetic analysis, acknowledges that
the data, which apply to only one gene, do not yield "a strong answer." But the
two lines of evidence taken together, says McFadden, "provide the first
explanation of parasite plastid origin," one consistent with secondary
The parasites' plastids add to growing evidence that endosymbiosis may have
happened "at least a half-dozen times" during the early evolution of cells,
says Palmer. Other researchers have found not only multiple membranes, but also
the remnants of an engulfed cell's nucleus, in two groups of algae, the red
Cryptomonas and the green chlorarachniophytes, implying that they got their
chloroplasts in the same way. And based on an as-yet-unpublished genetic
analysis of red and green algae, University of Washington botanists Benjamin
Hall and John Stiller suggest that green algae themselves may have arisen from
a cell that engulfed a plastid-containing alga.
But even though the new results help explain how the plastid got into
Toxoplasma and its relatives, they do not explain what it is doing there today.
It apparently does not carry out photosynthesis, having lost the genes required
to obtain energy from sunlight, as well as its chlorophyll. It does, however,
retain genes that may be involved in such crucial metabolic processes as the
manufacture of amino acids, which are the building blocks of proteins, and the
breakdown of lipids, which produces energy needed by the cell.
Biomedical researchers would like to pinpoint the plastid's critical functions,
because it might be possible to design drugs that block them with minimal side
effects for humans. Indeed, several drugs used to treat malaria and
toxoplasmosis may already be targeting the plastids. The drugs are thought to
inhibit protein synthesis, but researchers find no sign of inhibition in the
usual places--the cytoplasm or the mitochondria. The plastid, therefore, may be
the target, says Roos. To date, direct evidence that such drugs attack the
plastid has not surfaced, he says, "but it sure smells like it. It's very
close." If researchers have their way, whatever benefits the ancestral cell
derived from its potential dinner will end up as its Achilles' heel.
This article has been cited by other articles:
* Vercesi, A. E., Rodrigues, C. O., Uyemura, S. A., Zhong, L., Moreno, S.
N. J. (1998). Respiration and Oxidative Phosphorylation in the Apicomplexan
Parasite Toxoplasma gondii. J. Biol. Chem. 273: 31040-31047 [Abstract] [Full
Sci. Volume 275, Number 5305, Issue of 7 Mar 1997, pp. 1422-0.
Copyright © 1997 by The American Association for the Advancement of Science.
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