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Science  01 May 1998:
Vol. 280, Issue 5364, pp. 672

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    Genome Data Shake Tree of Life

    1. Elizabeth Pennisi

    New genome sequences are mystifying evolutionary biologists by revealing unexpected connections between microbes thought to have diverged hundreds of millions of years ago

    Over the past 3 years, the deciphering of the complete genetic codes of more than a dozen microbes has opened the way to a whole new understanding of how bacteria live and cause disease. “It's like being in a candy store,” says Richard Stevens, at the University of California, Berkeley. But on one front—the study of evolution—the information pouring out in the genome sequences has so far proved more confusing than enlightening. Indeed, it threatens to overturn what researchers thought they already knew about how microbes evolved and gave rise to higher organisms.

    For more than 2 decades, systematic biologists, led by evolutionist Carl Woese at the University of Illinois, Urbana-Champaign, have been using the sequences of RNA from the ribosomes—the cell's protein-making factories—to classify bacteria. One of the stunning successes of rRNA analysis was Woese's identification of one group of microbes, now called the archaea, as a third kingdom of life, adding to the two kingdoms already known: the true bacteria, which like the archaea don't have cell nuclei, and the eukarya, including higher plants and animals, which do (Science, 2 May 1997, p. 699).

    Since then, he and others have used rRNA comparisons to construct a “tree of life,” showing the evolutionary relationships of a wide variety of organisms, both big and small. According to this rRNA-based tree, billions of years ago a universal common ancestor gave rise to the two microbial branches, the archaea and bacteria (collectively called prokarya). Later, the archaea gave rise to the eukarya. But the newly sequenced microbial genomes and comparisons with eukaryotic genomes such as yeast have been throwing this neat picture into disarray, raising doubts about the classification of all of life.

    For one, because genes don't evolve at the same rate or in the same way, the evolutionary history inferred from one gene—say for rRNA—may be different from what another gene appears to show. “Before, people tended to equate rRNA trees with the [life history] tree of the organism,” says John Reeve, a microbiologist at Ohio State University in Columbus. “From the whole genomes, you very quickly come across [genes] that don't agree with the rRNA tree.”

    Even more perplexing, the newly unveiled genomes often contain a mix of DNAs, some seeming to come from the archaea and others from bacteria. “Features of both bacteria and archaea are turning up in eukaryotes, and to a surprising degree,” says Russell Doolittle, a molecular evolutionist at the University of California, San Diego.

    Many evolutionary biologists are coming to believe that these mosaics arose because genes hopped from branch to branch as early organisms either stole genes from their food or swapped DNA with their neighbors, even distantly related ones. The genetic oddballs may simply mean that the branches of the tree of life intertwine, but that the basic shape is sound. But if the gene swapping was extensive enough, the true branching pattern may be quite difficult to discern. Worse, the tree's “base” may turn out to be indecipherable: a network of branches that merge and split and merge again before sprouting the modern kingdoms. It may be, Woese concedes, that “you can't make sense of these phylogenies because of all the [gene] swapping back and forth.”

    Confounding genes

    The just-completed sequence of the bacterium Aquifex aeolicus, which lives at near-boiling temperatures, embodies the problems that molecular evolutionists are now confronting. To assess Aquifex's kinship to its fellow microbes, molecular geneticists Ron Swanson and Robert Feldman of Diversa Corp. in San Diego and their colleagues, who described the sequence in the 26 March issue of Nature, compared several of its genes with their counterparts in a range of species from the archaea and eukaryotes as well as other bacteria. The conclusion, Feldman reported in early February at the Conference on Microbial Genomes in Hilton Head, North Carolina, is that “you get different phylogenetic placements based on what genes are used.”

    The gene for a protein called FtsY, which helps control cell division, placed Aquifex close to the common soil microbe Bacillus subtilus, even though the two supposedly come from different branches of the bacterial tree. Even worse, a gene encoding an enzyme needed for the synthesis of the amino acid tryptophan linked Aquifex with the archaea. That wasn't the only anomaly the Diversa team found regarding the archaea, however. Their analysis of the gene encoding the enzyme CTP synthetase, which helps make the building blocks of DNA, spread the archaea out among all the other organisms evaluated, suggesting that they may not be as coherent and distinct a group as the rRNA tree implies. “It points to caution in terms of interpreting the 16s [rRNA],” Feldman concludes.

    The gene for FtsY and perhaps the gene for CTP synthetase might have been expected to tell a different story from the rRNA genes, because they have probably evolved at different rates. Woese picked the rRNAs to study because they are part of one of the cell's most basic activities—protein synthesis—and thus are unlikely to change radically. He hoped they would serve as a slow, steady clock. But genes not involved in such core activities, including those for FtsY and CTP synthetase, may evolve fast or slowly, depending on the different conditions microbes live in. “Each gene has its own history,” says Feldman.

    If differences in the way genes evolve account for some of the disparities between the patterns Feldman and his colleagues traced, the real tree of life might be worked out by overlaying different gene trees to come up with a consensus. “The sum of all these trees makes up the organism,” suggests biochemist Dieter Söll of Yale University in New Haven, Connecticut.

    But the tree Feldman derived from the gene for the tryptophan synthesis enzyme implies a more insidious problem: the possibility of widespread gene swapping among organisms, which could make arriving at a consensus tree quite difficult. Few researchers think Aquifex is kissing cousin to archaea, in spite of the similarity of their genes for this enzyme. The enzyme might be a relic from the ancestor common to both kingdoms, which has evolved unexpectedly slowly since then. But more likely, at some point, Aquifex took on the archaeal gene, substituting it for its own version, a process called lateral transfer.

    Gene swapping

    Not too long ago, attributing an unusual result to lateral transfer would have raised quite a few eyebrows. For years molecular evolutionists tended to use this idea to excuse irregularities in their attempts to construct phylogenetic trees, when actually their methods were at fault. But the microbial genomes have made the idea respectable.

    In one case last year, for instance, W. Ford Doolittle, an evolutionary molecular biologist with the Canadian Institute for Advanced Research in Halifax, Nova Scotia, scanned the genome of an archaeon called Archaeoglobus fulgidus, newly sequenced by The Institute for Genomic Research (TIGR) in Rockville, Maryland, with a computer program that searches new genomes for resemblances to genes in existing databases. The scan turned up an enzyme called a reductase that was much more like the reductases seen in bacteria than like comparable enzymes in other archaea and eukaryotes—supposedly the closer relatives of A. fulgidus.

    Similarly, an unusual gene that Söll, Yale biochemist Michael Ibba, and their colleagues first spotted in the genome of the archaeon Methanococcus jannaschii has since turned up in the Lyme disease pathogen, a spirochete called Borrelia burgdorferi. Because spirochetes are thought to be descendants of bacteria that had a different version of the gene, “we believe [it] arose from a lateral transfer,” Söll says, in which the spirochete took up an archaeal gene and lost its original one.

    Conversely, other researchers are finding archaealike genes in microbes classified as bacteria. Take Treponema palladium, the spirochete that causes syphilis. After Steven Norris of the University of Texas School of Medicine in Houston, working in collaboration with TIGR scientists, completed the Treponema genome last year, they noticed that its DNA contains genes for two particular ATPases—enzymes that break down adenosine triphosphate, often to release energy—known before to exist only in the archaea. And Treponema also has other genes that look suspiciously archaeal in origin, he reported at the microbial genomes meeting.

    Revising history

    In an upcoming issue of Trends in Genetics, Ford Doolittle proposes a new mechanism for this kind of gene swapping. He suggests that early eukaryotes may have gotten a significant part of their genomes from genes picked up by their predecessors from their food. As he puts it, “You are what you eat.”

    Assuming that the current tree of life is correct, he asks, how else can one explain Russell Doolittle's conclusions that 17 of 34 families of eukaryotic proteins that date back to early cell evolution look as if they come from bacteria, while only eight show a greater similarity to archaea, the supposed ancestor of eukarya. Terry Gasterland's team at Argonne National Laboratory, outside Chicago, Illinois, has made a similar finding: Twice as many yeast nuclear genes match up with bacterial genes as with archaeal genes.

    Although some modern bacteria are quite adept at taking up new genes—many pathogens develop antibiotic resistance this way—the successful incorporation of genes from food bacteria into eukaryotic genomes would be accidental and infrequent. But “we've got hundreds of millions of years for it to happen,” Ford Doolittle points out. Also, these genetic morsels are consumed with each meal, so that an incoming gene can have many opportunities to get into the genome and replace its native counterpart. In contrast, once a native gene happens to get removed from the host's genome, “it's lost forever,” he adds. Over evolutionary time, these processes would favor the loss of native genes and their replacement with borrowed ones.

    Woese thinks gene swapping was rampant even among life's earliest organisms. In his view, the organisms that lived before archaea, eukarya, and bacteria went their separate ways lived communally. “It was more like a consortium,” Woese says of this very early world. The ability to make use of a neighbor's genes would have proved an important advantage, he asserts.

    Members of this consortium may even have had different genetic codes. But the organisms that outlasted the rest would have been those that could make use of their neighbor's genes to adapt to changing conditions, says Woese. Over time, this advantage “ensured that the [DNA] code was universal,” he says, because those not able to read DNA-based genes could not survive as well as those organisms using DNA.

    This prehistoric commune might have worked well for early life, but it adds to the challenge for biologists trying to make sense of it all. With each descendent from this community “having taken up different things from the ancestor, you won't be able to draw clear trees,” Woese points out. He still has faith, however, that organisms roughly followed the patterns of evolution seen in changes in rRNA and that the three kingdoms will remain intact.

    However, the existence of so many genes that seem out of place has led some researchers to question whether eukarya descended from archaea. These researchers are also wondering whether archaea really are distinct from true bacteria, noting that although archaea were once considered limited to extreme environments, they are also turning up in the milder surroundings favored by true bacteria (Science, 24 April, p. 542). “I think it's open whether the three domains will hold up,” says Feldman.

    Despite the current ferment, however, Woese and others are confident that eventually a consistent picture of microbial evolution will emerge—even if what it might look like is uncertain, and even if its base is the mix of communal organisms Woese envisions. Within a year, some two dozen more genomes will be complete. At the same time, new software programs are refining researchers' ability to trace the heritages of different genes and discover more links between the three kingdoms. All this, says Texas's Norris, “will lead to a much better understanding of evolution as a whole.”


    Direct Descendants From an RNA World

    1. Elizabeth Pennisi

    The newly sequenced microbial genomes are causing biologists to reexamine the “trees” showing the evolutionary relationships among living entities (see main text). Among other things, the new findings are challenging the consensus that eukaryotes, organisms ranging from yeast to human that have nucleated cells, evolved from archaea—one kingdom of nonnucleated prokaryotes—rather than from bacteria, the other prokaryote kingdom. But a team in New Zealand has made an even more radical proposal about that early stage of microbial evolution. In the January Journal of Molecular Evolution, microbial evolutionary biologists David Penny, Daniel Jeffares, and Anthony Poole of Massey University in Palmerston North suggest that eukaryote-like cells actually predated the prokaryotes.

    The researchers began with the now well-accepted idea that the first life-forms lived in an “RNA world,” where RNA not only stored genetic information in primitive cells but also catalyzed the chemical reactions necessary for life, jobs now done primarily by DNA and proteins. Then they reasoned back from what is known about RNA metabolism in current organisms to discover what those first life-forms might have looked like. “The primary evidence for an RNA world comes from the roles of RNA in modern cells; these are considered relics or molecular fossils from an earlier living system,” Penny explains.

    Their quest led them to picture a mythical microbe they call Riborgis eigensis (for ribosomal organism), the last organism before genetically coded protein synthesis evolved. As the New Zealand team describes it, Riborgis looked in some ways more like a eukaryote than a prokaryote. Riborgis had linear chromosomes, as do eukaryotes, instead of the circular ones seen in most archaea and bacteria. That was necessary, Penny says, because Riborgis had an unsophisticated system for replicating its genome, and linear fragments could be handled more easily.

    But more important, Riborgis would have depended on RNA to carry out many functions, such as copying RNA or adding methyl groups to inactivate it. That reliance could have led to the evolution of RNA-protein particles similar to ribosomes and nuclear particles found in eukaryotes. This might have occurred, for example, if bits of Riborgis RNA happened to get translated into small amino acid sequences, and some of these eased the RNA's job by binding to the nucleic acid and stabilizing it. Over time, that advantage could then cause the RNA-based biochemistry to shift to a protein-based one like that found in modern prokaryotes. The protein-based systems are so much more efficient that Penny doesn't think the RNA-protein particles could have arisen later.

    The New Zealanders can't explain how the nuclear membrane—a defining feature of the eukarya—could have arisen in their ancestral organism. But to Carl Woese, an evolutionist at the University of Illinois, Urbana-Champaign, who agrees with many of the ideas put forth by Penny and other proponents of the RNA world, that may be the wrong question anyway. Instead, he suggests, we should ask “how did the cytoplasm arise?” As Woese points out, for all anyone knows, the nucleus may be the true descendent of the primitive organism that gave rise to eukaryotes, with the cytoplasm forming as this organism evolved a way to enclose and control its local environment.

    “The truth is we are all still arguing from ignorance and incomplete data sets,” agrees Russell Doolittle, a molecular evolutionist at the University of California, San Diego, who calls Penny's ideas “food for thought.” And although some argue that these events from 3 billion years ago will always be a mystery, Woese is optimistic. “Someday,” he predicts, “the facts will come along” to tell us what happened.


    X-ray Flickers Reveal a Space Warp

    1. David Kestenbaum

    If Earth had no atmosphere and no mountains, a satellite could orbit the planet at treetop level without falling. But Einstein's theory of gravity predicts that a very dense body, such as a black hole or a neutron star, bends space so steeply that objects orbiting closer than a certain point would slide catastrophically inward. Now x-ray signals from a distant neutron star have offered the first strong evidence for this smallest stable orbit. The findings, presented at a meeting of the American Physical Society in Columbus, Ohio, last week, offer a rare test of Einstein's theory in a strong gravitational field. They also offer new clues to the workings of these x-ray beacons.

    Neutron stars are only about 20 kilometers across, but they contain more mass than our sun. (Someone standing on the surface would weigh over a trillion kilograms.) In 1996, NASA's Rossi X-ray Timing Explorer satellite picked up rapid-fire x-ray flickers coming from some of these distant heavyweights. Most astronomers believe that the fastest flickers come from a long stream of material that spirals down to the star's surface from the innermost edge of a spinning “accretion disk,” producing a splash of x-rays. The x-rays emerge from the point where the material spills into the star. That point moves around with the accretion disk, so the x-rays rotate past Earth like a beam from a lighthouse.

    The flicker frequency rises whenever the inner edge of the disk creeps closer to the star and whips around it even faster. This may happen when a big chunk of material happens to fall in, throwing up a flare of x-rays but blocking some of the neutron star's radiation, which keeps the disk at bay.

    Hoping to spot the innermost orbit, astronomers spent a year watching a neutron star called 4U 1820–30 with the Rossi satellite. The group, from the NASA Goddard Space Flight Center in Greenbelt, Maryland, clocked the frequency of the beacon and watched its brightness, which told them how much material was falling in. As expected, when the beacon got brighter, the frequency increased. Then, to their delight, the brightness increased, but the frequency seemed to hit a ceiling at about 1000 cycles per second. It would go no higher, implying that no smaller orbit was possible.

    The group measured the ceiling on four different occasions, and they also saw it in a second, slower flicker, which originates as the accretion disk signal modulates another x-ray signal from a hot spot on the surface of the spinning star. “I'm convinced it's not a fluke,” says NASA Goddard's William Zhang, who presented the findings. Zhang says the innermost orbit is about 20 kilometers from the star's center.

    “These are extremely exciting results,” says Massachusetts Institute of Technology (MIT) physicist Paul Joss, explaining that the innermost orbit is direct evidence of the drastic warping of space-time expected near a massive object. Similar observations, says MIT physicist Wei Cui, could provide a stringent test for Einstein's theory. “Everyone assumes relativity is right,” he explains, “but there are so many theories of gravity around.”

    Most of these variants of relativity are indistinguishable from Einstein's except around dense objects like neutron stars. The innermost orbit, “literally a few kilometers above this strange object,” he says, is just the place where the theories' predictions might differ. If Einstein's theory is right, the position of the innermost orbit means the star's mass is about 2.3 times that of the sun. Unfortunately, there are no independent measurements of the mass to test that conclusion. But by studying other x-ray emitters, physicists may be able to confirm Einstein or rule out his competition.

    Relativity specialists aren't the only ones delighted with the data. The position of the innermost orbit implies that the neutron star is surprisingly hefty. By some estimations, that much mass packed into so small a volume should have collapsed into a black hole. The fact that it hasn't means that the strong nuclear force holding the particles apart is stronger than some had expected. “The nucleons want to stay farther away from each other,” staving off further collapse, says NASA Goddard physicist Jean Swank.

    University of Illinois astrophysicist Frederick Lamb is delighted with another feature of the data, the correlation between brightness and frequency. It supports his contention that the star's radiation plays a crucial role in controlling the infall of matter. “These data are like a dream come true,” he says. But he cautions that they “have only been around for 2 weeks. We need to kick the tires and see that they stand up.”


    Genes Put Mammals in Age of Dinosaurs

    1. Ann Gibbons

    It's hard to imagine humbler beginnings than those usually assigned to mammals. The long-standing view from the fossil record is that our furry ancestors first appeared 225 million years ago as small, shrewlike creatures living in the shadow of the dinosaurs. Only after a mass extinction 65 million years ago at the end of the Cretaceous period killed off the dinosaurs were mammals able to evolve into everything from primates to rodents to carnivores. But a new genetic study is challenging that view, saying mammals were already a diverse lot during the age of dinosaurs.

    In this week's issue of Nature, evolutionary biologist S. Blair Hedges and molecular evolutionist Sudhir Kumar of Pennsylvania State University, University Park, describe how they compared genes from hundreds of vertebrate species and used the differences as a molecular clock to date when animal lineages originated. The molecules show, say Hedges and Kumar, that the modern orders of mammals go back well into the Cretaceous period, in some cases to more than 100 million years ago. “The thought of all these different creatures living under the feet of the dinosaurs is intriguing,” says Hedges.

    But many paleontologists are deeply skeptical. “It suggests that the fossil record is horribly incomplete,” says Michael Benton, a paleontologist at the University of Bristol in the United Kingdom. “They're saying side by side with lower Cretaceous dinosaurs, we should be finding ducks and hens and squirrels and rabbits.” Instead, he thinks that the molecular clock can't keep time.

    The new report is the latest of several molecular studies to suggest that many animal lineages are older than the fossil record shows (Science, 21 February 1997, p. 1109). Most of these studies have relied on just a handful of genes and have not persuaded many doubters. But Hedges and Kumar analyzed a prodigious number of genes—658 in all—and counted sequence differences between 207 vertebrate species. They assumed that the more differences between two species, the more time had passed since they diverged from a common ancestor. To calculate how fast the molecular clock ticks, the team started with a reliable date from the fossil record: 310 million years ago, when the mammal-like reptiles split from the birdlike reptiles. From the sequence differences seen between animals in these two groups, the team calculated a rate of change for each gene, then used those rates to calculate divergence times among other species of vertebrates.

    For most species, the molecular dates matched those from fossils—but not for mammals. According to the genes, the modern orders of mammals arose much earlier than expected. Marsupialia (kangaroos and opossums) are pegged as originating 173 million years ago, rather than 94 million years as indicated by fossils, and Archonta (primates and tree shrews) at 86 million years ago, rather than 64 million years ago. “This doesn't mean that elephants and tigers were running around,” says Hedges. “The animals themselves were probably small. But the lineages leading to different modern orders of mammals were already distinct.”

    Paleontologist Philip Gingerich of the University of Michigan, Ann Arbor, however, protests that if the molecules are right, the fossil record has a gap as big as 70 million years. “You can imagine how maddening this stuff is to a paleontologist,” he says.

    The missing mammals may have been overlooked because they were small and harder to find, or because they were scarce and lived in terrain less likely to be preserved, suggests Hedges. But Benton says that's unlikely because the Cretaceous fossil record reveals many lizards, snakes, birds, and other small vertebrates. And paleontologists have turned up only a few controversial Cretaceous specimens linked to modern mammals (Science, 21 November 1997, p. 1438), although they have hunted intensely. “There's a huge premium on finding a Cretaceous rabbit or other mammal,” says Benton.

    Instead, most paleontologists argue that the molecular clock is unreliable. Perhaps the mutation rate sped up and slowed down at different times in mammalian history, suggests Benton. For example, a population explosion during the rapid radiation of mammals 65 million years ago might have allowed their DNA to accumulate mutations more quickly, speeding up the clock.

    But Hedges and other molecular evolutionists say their clock is reliable, noting that their study agrees with most dates from the fossil record and with other genetic work. “It's entirely consistent with what we found,” says Simon Easteal, a molecular evolutionist at Australian National University in Canberra who also found earlier origins for mammals. And if the clock sped up during the early mammalian radiation, then the later dates for divisions between various mammalian species, such as primates, sheep, and cows, wouldn't match those from fossils—unless the clock later slowed down by precisely the same amount in each of many different lineages. “That is really stretching,” says Hedges.

    For now, the debate goes on. “We have two fairly entrenched positions,” says Benton. “The exciting thing is within our lifetimes, we can hope to see which one is right.”


    New Clue to How Anthrax Kills

    1. Evelyn Strauss
    1. Evelyn Strauss is a free-lance writer in San Francisco.

    The deadly disease anthrax has been much in the news lately—thanks largely to fears that rogue leaders or international terrorists will attempt to wage germ warfare with the anthrax bacillus. Now, a research team led by George Vande Woude at the National Cancer Institute (NCI) in Frederick, Maryland, has made a serendipitous discovery that may someday give doctors a new countermeasure against the disease.

    On page 734, Vande Woude and his colleagues report that they have identified a possible mechanism of action for “lethal factor” (LF), a toxic protein produced by the anthrax bacillus that is thought to be one of the principal causes of death in infected individuals. Scientists have long suspected that LF is a protease, an enzyme that cuts other proteins, but they have not been able to identify its targets. The Vande Woude team has found that LF cleaves and inactivates an enzyme in one of the cell's key signaling pathways, the mitogen-activated protein kinase (MAPK) pathway, which helps control cell growth, embryonic development, and the maturation of oocytes into eggs.

    Although it makes sense that disrupting such a critical pathway could kill cells, researchers have not yet shown that this effect is what makes LF so toxic. Regardless, the result may aid the development of new treatments that work by neutralizing the toxin. As Vande Woude puts it, “Conceivably, we could find a drug that would make anthrax as a weapon of destruction as powerful as a water pistol.”

    He and his colleagues had no intention of studying anthrax pathogenicity. They were interested in the MAPK pathway, named for one of its constituents, a so-called kinase that regulates the activity of other molecules by attaching phosphate groups to them. To find out more about the pathway's role in oocyte maturation, Nick Duesbery, a postdoc in Vande Woude's lab, was seeking compounds that block MAPK's activity. The group knew of one such chemical, PD09859, which is one of more than 60,000 agents the NCI has screened for antigrowth activity on human tumor cell lines. The Vande Woude team asked NCI chemist Ken Paull to search that database for other compounds with effects similar to PD09859's. LF proved to have the highest score.

    Working with LF provided by anthrax researcher Steve Leppla at the National Institute of Dental Research in Bethesda, Maryland, Duesbery and colleagues then showed that the toxin prevents frog oocytes from maturing into eggs, indicating possible blockage of the MAPK pathway. The jam apparently happens, the researchers found, because LF clips off a piece of the enzyme responsible for activating MAPK, thereby crippling it. When they sequenced two forms of this enzyme—MAPK kinase (MAPKK)—from LF-treated cells, for example, they found that the amino terminals of the proteins were missing either seven or nine amino acids.

    Biochemist John Collier at Harvard University Medical School in Boston says that killing the host may be a key advantage of targeting this essential molecule. Unlike many microbial pathogens, Bacillus anthracis seems to depend on the death of its host to propagate. “As the animal decays, the bacteria are exposed to oxygen; they turn to spores and repopulate the soil,” says Collier. “The host has to die for transmission to occur.”

    The identification of an LF target molecule represents the first step toward developing an antidote to the toxin. Natural anthrax infections, which are usually transmitted by animal products, are rare, but having such an antidote could be a boon if the pathogen were to be used in a terrorist attack. Although antibiotics kill B. anthracis, by the time characteristic symptoms appear, the bacteria are already multiplying wildly in the bloodstream and have produced massive amounts of circulating toxin, which can't be eliminated by killing the bacteria. Antibiotic treatment at this point doesn't help. “A drug that inhibits LF enzymatic activity might be able to act very quickly to block any further effects of LF on susceptible cells,” says microbiologist Randall Holmes at the University of Colorado Health Sciences Center in Denver.

    Still, the researchers aren't certain that LF owes its toxicity to its ability to cleave MAPKK. In fact, it's hard to explain how inactivating MAPKK would result in some of the known physiological effects of LF. In 1993, for example, Collier and Philip Hanna, currently at Duke University Medical Center in Durham, North Carolina, found that immune cells called macrophages mediate the harmful effects of LF in mice at least partly by producing inflammatory cytokines, immune cell-activating molecules that in excessive concentrations can cause some of the toxic reactions, including shock, seen in anthrax. Duesbery is now looking to see whether MAPKK inactivation is linked to overproduction of these compounds.

    To try to show directly that MAPKK inactivation is responsible for LF's physiological effects, he is also investigating whether a MAPKK mutant that resists cleavage by LF can protect cells from the toxin. At the same time, the team is looking for other cellular substrates of LF.

    As they pursue the many questions their findings have generated, the researchers seem to be enjoying the adventure. “I started out as a virologist and ended up studying oocyte maturation,” says Vande Woude. “Now suddenly I'm looking anthrax in the face. It's pretty amazing.”


    Bison Prime Prairie Biodiversity

    1. Jocelyn Kaiser

    Nostalgia may be one good reason for restoring bison to the North American plains, but now there's a scientific incentive as well: Bison appear to help keep grassland ecosystems healthy. Findings from a 10-year study in Kansas linking bison grazing to plant diversity in tallgrass prairie offer hope to land managers trying to preserve the last remnants of native U.S. grasslands. “Potentially there are ecological solutions to some of these biodiversity problems,” says study leader Scott Collins of the National Science Foundation.

    The study, described on page 745, may also put cattle grazing in a slightly better light. That's a hot-button issue in the U.S. heartland, where environmentalists contend that cattle are driving to extinction native plants on public lands. But some scientists worry that the message might be carried too far. “The danger is that people will manipulate these results into advocating more [cattle] grazing,” says Stephen Torbit, a senior scientist with the National Wildlife Federation in Boulder, Colorado.

    About 10% of North America's original tallgrass prairie remains in scattered patches from Illinois west to Nebraska and from Texas up to southern Canada. Ecologists know that fires—whether set by lightning or by people—kept the bison-filled prairies from turning into forests for millennia. Land managers now try to mimic those conditions by burning prairies in the spring to check woody growth and exotic species. But civilization poses a new, grave threat to tallgrass ecosystems worldwide: Atmospheric nitrogen from car tailpipes and fertilizers deposited onto prairies is helping some species flourish at the expense of others, on balance lowering the prairies' biological diversity (Science, 13 February, p. 988).

    Hoping to better tease out the delicate relationship between burning, nitrogen, and grazing, scientists at Kansas State University in 1986 launched an experiment on 20 144-square-meter plots of grassland at the Konza Prairie Long-Term Ecological Research site in northeastern Kansas. They plied some of the plots with heavy doses of nitrogen, torched others once a year, did both to a third set of plots, and left the rest alone. They also mowed two sets of plots each June to simulate grazing by bison, which tend to nibble at a patch for a while then move on.

    The team found that by 1994, the burning and added nitrogen had taken a heavy toll. Tallgrass prairie is a mixture of so-called C4 grasses, which grow better in warm, dry conditions, and C3 species, which prefer cooler, wetter digs. Although C4 grasses thrived on the burnt, nitrogen-rich plots, C3 plants were decimated, leaving these plots with roughly 5.6 species per 10 square meters—66% fewer than the control plot.

    The story was much different in plots that had also been mowed, however: The number of species didn't fall off at all. The researchers got similar results when they compared burned and unburned Konza Prairie watersheds where bison had been reintroduced in 1987. The reason, Collins says, seems to be that the taller C4 grasses “form this big, thick canopy in which a lot of the less common species can't survive. Mowing or grazing shaves open that canopy and allows more light to get through, so a lot more species can coexist.” That finding “is a significant advance in our understanding of what controls prairie composition,” says ecologist David Tilman of the University of Minnesota, St. Paul.

    The implications for cattle grazing are unclear, however. Rangeland ecologist William Lauenroth of Colorado State University in Fort Collins says the new findings represent “the first time a group of ecologists with no clear connection to the livestock grazing community” agree with range scientists that grazing can benefit prairie grasslands. But other experts say prairie-reserve managers shouldn't move too quickly to adopt mowing or grazing as a tool to manage biodiversity. For one thing, the impact may differ depending on which big galumph—a bison or a steer—is chewing up your prairie. Bison tend to range more widely than cattle, which if left in a field long enough are more likely to chomp it down to the roots.

    Indeed, no one wants to see a stampede to open up protected grasslands to cattle grazing. The problem is that grazing—even by bison—“can be very bad for grasslands” that are already degraded, Collins says. The best approach, he and others say, is to allow moderate bison or cattle grazing on healthy prairies and track how the ecosystems respond.


    'Monogamous' Gibbons Really Swing

    1. Ann Gibbons

    Salt Lake City—The sex and social lives of gibbons were long thought to be about as exciting as those of June and Ward Cleaver. Like a 1950s-style nuclear family, gibbons were thought to live in stable groups of five or six, in which a mom and pop mate for life and raise their offspring. Family comes first, and the only excitement comes when the group spars with the neighbors. “The impression was they were monogamous and not very social with other groups—therefore, that they were fairly boring,” says Thad Bartlett, an anthropologist at Dickinson College in Carlisle, Pennsylvania.

    But in a report here last month at the annual meeting of the American Association of Physical Anthropologists, Bartlett showed that gibbons are anything but boring. He and others have found that although many gibbon pairs mate for years on end, like human families of the ‘90s they have plenty of drama—infidelity, divorce, abandonment, and step-children from other unions, as well as much socializing and kinship among members of different groups. The findings show how important it is to explore what “monogamy” means for primates, and underscore the social complexity of these intelligent animals. “Gibbons really have been the prototype for monogamous primates,” says Phyllis Dolhinow, a biological anthropologist at the University of California, Berkeley. “It turns out things just aren't as tightly structured as had been assumed.”

    The new view of gibbon family life is emerging from a fresh crop of long-term studies. For example, Bartlett, who presented his findings at the meeting, tracked two groups of white-handed gibbons (Hylobates lar) intensively for a year in the Khao Yai National Park in a seasonal tropical forest north of Bangkok, Thailand. These apes have been studied off and on for 15 years by ecologist Warren Brockelman at Mahidol University in Bangkok and his colleagues, so they are accustomed to humans; Bartlett thinks that this allowed the animals to relax and exhibit social behaviors not seen before.

    Researchers had thought that gibbon families, although stable, were always territorial and hostile to neighbors, but the Thai gibbon families socialized with one another. In fact, one group spent 25% of its encounters with three other groups in “affiliative,” or friendly, encounters, where the juveniles played and groomed each other. Most surprising, one adult male groomed and played with juveniles from another group. When Bartlett checked the long-term records on the groups, he realized that the friendly adult was an uncle of the neighboring juveniles, implying that the male had switched groups. “Their social relationships are a lot more complex than we'd assumed,” says Bartlett. “They are migrating into groups that are not very far away, and there's a complex awareness of who is in the neighborhood.”

    This sociability also extended to mating habits. One young male left his group to move in with neighbors, where he began singing the characteristic mating duet with the adult female; he eventually supplanted her older male companion. This backs up work by primatologist Ryne Palombit of the University of Pennsylvania, Philadelphia, who recently studied gibbons at the Ketambe Research Station in Sumatra, Indonesia, for 6 years. He saw one female leave her group to join a newly widowed male, where she stayed for several months, mating with him and several other males before returning to her original mate. “All the textbooks say you have a male and female who are monogamous,” says Palombit. “What we saw is that there may be a male and female, his brother, her sister, her daughter, his son. It's just very complicated, and the rigid nuclear family model is insufficient.”

    Instead, a new model is emerging of a “non-nuclear” family, where mates sometimes come and go, and the offspring from different unions grow up together. At least for gibbons, it seems that monogamy can be a lot more interesting than humans ever imagined.


    Last Hurrah for an Infrared Satellite

    1. Govert Schilling
    1. Govert Schilling is an astronomy writer in Utrecht, the Netherlands.

    When the temperature climbs beyond 2 degrees above absolute zero, it gets uncomfortably warm for an infrared satellite. The European Infrared Space Observatory (ISO) reached that point early last month after it finally ran out of coolant and had to quit its measurements of the feeble heat radiation from the rest of the universe. Sometime about mid-May, engineers at the European Space Agency's (ESA's) ground station in Villafranca, near Madrid, will shut it down for good.

    “This is a time for celebration, not sorrow,” says ESA science director Roger Bonnet. ISO lived for 10 months beyond its expected 18-month lifetime, collected more than 26,000 observations from Earth's astronomical backyard to the far reaches of the universe, and made several important findings during its final days. “It's been a spectacular success,” says Reinhard Genzel of the Max Planck Institute for Extraterrestrial Physics in Garching, Germany, who chairs ESA's astronomy working group.

    Cooled by over 2000 liters of superfluid helium, ISO's sensitive detectors were able to study the infrared glow of “the icy, dusty, rocky, and molecular universe,” as Bonnet puts it, as opposed to the hot, gaseous universe that emits visible light. In just a few of its research highlights, ISO studied colliding galaxies, discovered crystalline silicate grains in protoplanetary dust disks, and found huge quantities of interstellar water vapor in the Orion Nebula (Science, 17 April, p. 378).

    As one of its last feats, ISO picked up the infrared signature of water in the chilly atmosphere of Titan, the largest moon of Saturn. Although it's a minor constituent of the nitrogen-rich atmosphere, water vapor “makes the already complex story of the atmosphere of Titan … a little more enticing,” says Carolyn Porco of the Lunar and Planetary Laboratory of the University of Arizona, Tucson. The finding, by a team headed by Athena Coustenis of the Paris Observatory and Alberto Salama of the ISO Science Operations Center at Villafranca, implies that water is being delivered into Titan's atmosphere from some outside source, Genzel said at a press meeting in London last month.

    “The chances are next to nil for the ISO-observed water vapor to be derived from the [extremely cold] surface of Titan,” agrees Porco. “A good candidate is cometary impact. But it may not be the whole story.” Porco, who is principal investigator for the camera on board the Cassini spacecraft bound for Saturn and Titan, thinks the icy rings of Saturn might also be shedding water into Titan's atmosphere, “though I don't think anyone has given this serious consideration.”

    Farther afield, ISO also took a long look at a small patch of sky called the Hubble Deep Field South. In late October, the Hubble Space Telescope will observe this tiny region continuously for many days to spy on faint galaxies in the distant universe, repeating an observation it made more than 2 years ago in the northern sky. ISO's detailed image gives a preview of what Hubble may see. The image swarms with galaxies that are surprisingly bright in the infrared, just as an earlier ISO image of Hubble Deep Field North had shown. The galaxies must be ablaze with newborn stars, which are hidden from optical detectors behind shrouds of dust. What's more, says team member Sebastian Oliver of Imperial College London, “we've detected at least one galaxy with no known visible counterpart.”

    Even after the temperature of ISO's detectors became too high for most of its instruments to operate, the Short Wave Spectrometer, built by the Groningen laboratory of the Space Research Organization Netherlands, soldiered on into the second half of April, collecting data on “standard stars” to extend an existing star classification scheme into the infrared. And ISO's death will mean only a pause for space-based infrared astronomy. Future orbiting observatories, like NASA's Space Infrared Telescope Facility and ESA's Far Infrared Space Telescope, scheduled for launch in 2001 and 2005 respectively, will extend ISO's harvest of observations, which now fill nearly 1000 CD-ROMs.


    Deep-Sea Coral Records Quick Response to Climate

    1. Richard A. Kerr

    Paleoceanographers—the historians of Earth's oceans—have always been at a serious disadvantage compared to the physical oceanographers who document the present. They can't launch current meters to measure how water masses with different heat and salt content stirred past oceans. Instead they have had to content themselves with reading chemical and isotopic clues from sediment records, which hint at the location and depth of particular water masses in the past. These snapshots couldn't say how fast the water was moving and thus how it might interact with the atmosphere to form the climate system.

    Now oceanographers have found that by analyzing deep-sea corals, they can replace those snapshots with a motion picture. By measuring a carbon isotope trapped in precisely dated corals, they can assemble a record of the currents flowing through the ancient ocean. And the first use of this new kind of record provides the best evidence to date for an idea long espoused by climate modelers: When climate changes, ocean circulation can suddenly shift and perhaps feed back to affect climate.

    Coralline current meter.

    Deep-sea corals only a few centimeters across reveal circulation changes in the ancient ocean.


    On page page 725 of this issue of Science, paleoceanographer Jess Adkins of Columbia University's Lamont-Doherty Earth Observatory in Palisades, New York, and his colleagues report that coral dredged from thousands of meters down shows that as the last Ice Age began to wane 15,000 years ago, the deep currents bathing the western North Atlantic changed in less than 160 years. Besides demonstrating that the deep ocean can respond quickly to climate change, the finding shows that deep-sea coral—much of which is now gathering dust in storage—“is a stupendous archive,” says paleoceanographer Scott Lehman of the University of Colorado, Boulder. Given enough samples from around the world, “you'd be doing real physical oceanography in the past, something we've never been able to do.”

    Opening a new field to paleoceanographers required a bit of luck and some perseverance. Researchers have been hauling up rocks from the sea floor for decades to study the ocean crust, but the centimeter-sized, solitary-living deep-sea corals that came along for the ride were often ignored and even discarded when storage space got tight. But after hearing a 1993 talk by coral expert Michael Risk of McMaster University in Hamilton, Ontario, oceanographer Edward Boyle of the Massachusetts Institute of Technology (MIT) and Adkins, then his student, also began to consider the potential of deep-sea coral to serve as a paleoceanographic record. Unlike sediments, the traditional paleoceanographic record keepers, corals are relatively easy to date precisely with isotopic methods, and they aren't stirred by burrowing animals, so they have finer time resolution.

    Starting with hundreds of samples from several collections, Boyle and Adkins first had to find a way to quickly and inexpensively identify coral that grew at a time of particular interest. They roughly dated more than 100 corals by counting the radioactive decay products of uranium-238 with an economical mass-spectrometry method. They identified four corals that grew about 15,000 years ago, about 1800 meters down on the slope of Kelvin seamount in the western North Atlantic. Then they used a second, more precise mass-spectrometry method on uranium decay products to date these four with a precision of 200 years or less.

    Adkins and his colleagues also measured the amount of radioactive carbon-14 remaining in the coral. Carbon-14 is often used for dating corals, but in deep-sea samples it holds clues to ocean circulation. Cosmic rays create carbon-14 in the atmosphere, so this isotope's abundance in seawater begins to decline as soon as the water sinks below the surface. Adkins could use the carbon-14 “clock” to estimate the interval from the time the water sank to the time it delivered carbon to the coral—a measure of how fast deep water masses were forming.

    The carbon-14 levels showed that the four corals lived through a major circulation shift 15,400 years ago. By tracing isotopes along the growth layers of the corals, the team saw a decline in carbon-14 abundance from their oldest parts to their youngest—a period of less than 160 years, according to estimates from living deep-sea coral. That decline signals a switch in ocean circulation, implying that the corals were exposed to “older” water—water that had last seen the surface a relatively long time before. Adkins thinks the lower carbon-14 level is a signature of so-called Antarctic Bottom Water, which sinks in Antarctica and so had traveled the globe before reaching the corals. In less than 160 years, he thinks, it had replaced another mass that had sunk nearby in the North Atlantic.

    Other indicators are consistent with that idea. They suggest that warmer, more saline surface waters were shifting northward—early signs that the ice age was losing its grip, although no one is sure whether climate or circulation changed first. Saline water is denser and more prone to sink, so the changes at the surface may have let the North Atlantic water sink below the 1800-meter depth of the corals, allowing the Antarctic water mass to move in.

    “The corals are some of the first proof that the deep ocean can change very quickly,” says Adkins. “The deep ocean can readjust itself almost as quickly as the atmosphere and ice.” For years, ocean modelers have been warning that in a warmer, nonglacial world, deep-water formation in the North Atlantic might abruptly grind to a halt. That would have serious consequences for climate, because the sinking draws warm surface water northward, warming Europe and starting a circulation that affects climate worldwide. But this is the first time researchers have actually gathered evidence of such dramatic, rapid changes in the real ocean. “The importance of these corals as climate recorders can't be overemphasized,” says Risk.

    The study also opens a window on the rates of ancient ocean circulation. For example, Adkins suggests, on the basis of both the isotopic and chemical properties of the corals, that the Antarctic water took 500 years to travel to Kelvin seamount, about 400 years longer than today. That implies more sluggish deep-water formation. If Antarctic samples confirm that finding, researchers might be able to gauge how fast heat was being pumped through the oceans, a vital clue to the ancient climate system. For the thousands of ancient deep-sea corals hidden away in dusty storage rooms, this study offers a new lease on life.

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