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Elizabeth Culotta: May 2009 Archives

LONG ISLAND, NEW YORK—After an evening that touched on Darwin and the evolution of fish, ants, and humans, the "Evolution: The Molecular Landscape" symposium at Cold Spring Harbor Laboratory was true to its title and headed into the RNA world first thing the next morning. Or rather, the ribonucleoprotein world. Ribonucleoproteins (RNPs) are complexes of RNA and proteins. Many researchers are convinced that the first life depended on RNA and that proteins came later. Those proteins eventually squeezed out RNA from most of its roles carrying out the molecular processes needed for survival. But proteins—or at least simple peptides—were likely in the mix from the very beginning, said Thomas Cech of the University of Colorado, Boulder. He added that "it was never an RNA world." Moreover, it's not just a protein world today. There is increasing appreciation for the amount of RNA transcribed from the genome that doesn't code for proteins. Thus, in partnership with proteins, RNA continues to figure largely in cellular function. A look at RNPs shows that there is a give-and-take between the two partners in the roles they play in the complex.

The discovery of the first ribozymes—RNA enzymes—in 1982 had provided a way out of the chicken-and-egg problem of which came first, proteins or nucleic acids, such as RNA, because today both types of molecules are critical to life. Life started with RNA, then proteins and DNA came along later and outdid RNA as arbiters of biological reactions and information carriers, respectively. Ribozymes evolved into RNPs, which gradually lost their RNA components to produce modern protein enzymes (see diagram). riboBut "we don't see RNA disappearing," Cech said. Instead, it's proved surprisingly versatile.

Cech argues that the same abiotic conditions that favored the formation of nucleic acids likely also favored small peptides. On its own, RNA is so-so as a catalyst, but in RNPs, it continues to play a vital role. The same synergy likely existed in those earliest days, he says.

Take the ribosome. "They are the Trojan horses that came out of the RNA world," said Venki Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom. Every molecule in the cell is made by the ribosome or by a protein produced by the ribosome. Over the past decade, he and others have worked out that the RNA subunits are at the core, controlling the assembly of amino acids into specific proteins. Its protein partners help hold two RNA subunits in a semirigid structure that shifts back and forth to pull in amino acids and push out the emerging protein chain.

The rigidity of the ribosome is a sharp contrast to telomerase, which was found to be an RNP in 1987. Telomerase typically consists of one RNA and several protein subunits, including a reverse transcriptase protein called TERT that extends the ends of replicated chromosomes to keep them from getting shorter each time they are copied. The RNA specifies the bases that TERT adds. But Cech's group has found that RNA also acts as a flexible scaffold that recruits other proteins, such as a DNA repair protein called Ku. When they alter the RNA so that it doesn't bind Ku, telomerase doesn't work as well. When they add an extra binding site on the RNA for Ku, then chromosomes grow extra-long, he said. The RNA's arms are flexible and swing into different positions. Yet in the lab, Cech's crew has shortened these arms without affecting the RNP's function. "It's a dynamic system where proteins can switch in and out," says Cech.

Both the ribosome and the telomerase show signs that the protein-RNA partnership is dynamic over evolutionary time as well. Cech and his colleagues have discovered that there is a part of the telomerase RNA that helps speed telomerase activity. "He's finding new functionality in the RNA," says Susan Lindquist of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. "A new region has come in and contributes to catalysis."

In the ribosome's case, proteins are lending the helping hand. Ramakrishnan reported the discovery of an arm of one of the ribosomal proteins that extends deep into the RNA where transfer RNAs bind and deliver amino acids. Now instead of depending on RNA alone, "protein tentacles are assisting the process," says Ramakrishnan. In mitochondrial ribosomes, proteins have taken on an ever-larger role. The ratio of RNA to protein in the cell's ribosomes is 2 to 1; but in mitochondrial ribosomes, the ratio is roughly 1 to 2. This ribosome looks about the same, but most RNAs have been replaced by protein, leaving just a small RNA core.

These examples show that RNPs "are not decaying," says Lindquist. "They are continuing to evolve."

—Elizabeth Pennisi

Illustration credit: Harold White, University of Delaware

After receiving the red-carpet treatment in New York City and London (Science, 29 May, p. 1124), the fossil primate known as Ida returned home to Oslo this week, where she will appear at the University of Oslo Natural History Museum starting 5 June. Meanwhile, life-size casts of Ida are already on display at the American Museum of Natural History in New York City and the Natural History Museum in London—and others will soon appear at museums in Germany, not far from the Messel pit where the 47-million-year-old fossil was found, according to paleontologist Jørn Hurum of the Oslo museum.

The fossil of an ancient adapid primate formally named Darwinius masillae was unveiled by Mayor Michael Bloomberg in New York City on 19 May. In one remarkable week, Ida was the subject of a media blitz worthy of the winner of American Idol. First, she starred on 25 May in The Link, a documentary film shown by The History Channel in the United States. The next night, Ida appeared in London with the filmmaker Richard Attenborough, who narrated the version of the film shown on BBC One in England on 26 May. By the end of the week, she was the first fossil to be featured on Google’s home page and the subject of a companion book to the documentary and a Web site.

But one group was conspicuously absent in the toasts to Ida’s success: the scientists who are the world’s experts in primate evolution. Even though they were impressed by how complete and well-preserved the fossil primate was, many were troubled by the branding of Ida as a “missing link” to humans (ScienceNOW, 19 May). Most complained that Ida was the ancestor of lemurs, not humans, and that the hype was not justified by the analysis provided in the scientific paper published last week in the online journal PLoS ONE. The uncovering of Ida’s true identity, however, failed to rain on her parade: At least 2 million viewers tuned in at 9:00 p.m. EDT on 25 May to watch Ida on The History Channel, according to Nielsen Fast Cable ratings. That is up 67% compared with The History Channel’s prime-time average.

—Ann Gibbons

Symp2009_mockup.jpg LONG ISLAND, NEW YORK—Leave it to Cold Spring Harbor Laboratory (CSHL) to put molecules center stage at Darwin’s birthday party. Home to Nobel laureates such as DNA discoverer James Watson and corn geneticist Barbara McClintock, the lab plays host this week to 390 researchers for "Evolution: The Molecular Landscape" (27 May to 1 June). The theme stands in sharp contrast to when the lab last toasted Darwin, in 1959. Then "what was absent was any reference to molecules," says CSHL meeting organizer Jan Witkowski.

One of dozens of Darwin conferences taking place around the world to celebrate the 200th anniversary of Charles Darwin's birth, this event is billed as more of a scientific meeting than a celebratory one, billing 75 talks and 200 posters. The meeting is the lab's 74th annual symposium—originally a monthlong mix of research and presentation and now an annual 5-day themed meeting. It usually takes a year to plan, says CSHL meeting organizer David Stewart. But this time, he and Witkowski started 6 months early, anticipating that many meetings would be vying to book evolutionary biology's biggest names. They succeeded: The program reads likes a "Who's Who" in biology—with luminaries such as Edward O. Wilson and Thomas Cech on the program.

The opening session reflected more than just molecules and gave a flavor of the diversity of topics yet to come. First up was a close look at Darwin himself. Darwin scholar Janet Browne of Harvard University emphasized Darwin as an experimentalist who tapped into a far-reaching network of friends and relatives as collaborators. "He turned his house and garden into a domestic version of a modern research lab … in an age when laboratories were hardly in existence," Browne said. Darwin relied on simple tools. For example, a chemical balance from his youth and tin plant markers sufficed for his studies of what and how carnivorous plants ate. And he used household chemicals—wine, beer, ammonia, urine, nicotine—in those experiments.

Yet Darwin was also an early scientific celebrity. During his day, fans could buy portraits and paintings of their favorite naturalist. Songs, children's books, even Wedgwood china and a "gargling oil" had Darwin themes. Cartoonists depicted him as part human, part ape. And his theories overshadowed his research. His book On the Origin of Species "clouded everybody's view of what he was up to," says Browne. Darwin nonetheless cultivated collaborations across the globe—some 14,000 letters still exist—and solicited from these colleagues their own thoughts and observations about problems he was pursuing. "Letters were a major vehicle of scientific communication," said Browne.

—Elizabeth Pennisi

Photo credit: CSHL 74th Symposium and Daniel Smith

According to J.R.R. Tolkien, “The beginning of hobbits lies far back in the Elder Days that are now lost and forgotten.” But what of the origins of the puzzling, meter-tall hominid that walked our own Earth a mere 17,000 years ago? Among scientists, three hypotheses are still in play for how this creature came to live on the Indonesian island of Flores. One idea is that members of Homo erectus landed on the island and the species' brain and body shrank over time in an evolutionary process called insular dwarfing. Another hypothesis suggests that the hobbit’s ancestor was even more primitive—and therefore smaller brained—than H. erectus. And some researchers still argue that the most complete hobbit specimen and associated skull are merely those of a diseased modern human. The first and second hypotheses get independent support in this week’s issue of Nature on topics ranging from feet to hippopotamuses. (Skeptics continue to argue for pathology, although no recent papers from them have appeared.)

jungers.nature.5.09.image2 In the first Nature paper, William Jungers of Stony Brook University in New York and co-authors describe the surprisingly primitive feet of the creature they call Homo floresiensis; this work was also presented at a meeting last year (see Science, 25 April 2008, p. 433). Jungers found that H. floresiensis had big feet compared to its short legs (see foot and tibia, left), a short big toe and flat feet, and was probably a poor runner who walked with a high-stepping gait. Jungers says the foot and other aspects of the skeleton hark back to a very early Homo species or even the australopithecines who lived 2 million or 3 million years ago in Africa. Some of these features are more primitive than those of H. erectus, suggesting either a more ancient ancestor or unusual evolutionary reversals to primitive traits, he says. “If it’s an insular dwarf, then it’s got reversals from head to toe,” Jungers said at a recent meeting.

E_WESTON_NatureLIve.18/6/08ppt copy.ppt Not so fast, say Eleanor Weston and Adrian Lister of the Natural History Museum in London, authors of the second Nature paper. The problem with the island-dwarfing hypothesis has been H. floresiensis's tiny brain of about 417 cubic centimeters, roughly the size of a chimpanzee’s. Past studies have suggested that when mammals shrink in body size, brain size is only moderately reduced. Weston challenges that view with a hefty chunk of data from hippos. She studied the brains and sizes of fossils of two species of dwarf hippo on the island of Madagascar and compared them to their normal-sized hippo ancestor on the mainland (see ancestor, above left, and a dwarf descendant shown at roughly the same scale). The brains of the Malagasy hippos were quite small—about 30% smaller than predicted if the mainland ancestor had shrunk proportionately. “The hippos are reducing their brain size in a way we never predicted,” says Weston. “It’s mechanistically possible to reduce brain size much more than we thought.”

The pair then turned to H. floresiensis and found that if the Flores skull followed the hippo scaling rules, it could be descended from several smaller H. erectus individuals, including those from Dmanisi, Georgia, and from Africa. “You don’t need to rule out Homo erectus as an ancestor,” said Weston. She theorizes that in addition to reducing size, island dwarfing could also lead to the appearance of primitive traits. There are examples of young mammals retaining primitive traits, she says, and adult insular dwarfs may incorporate the juvenile stages of their ancestors and so end up looking primitive. She urged paleoanthropologists to explore whether H. floresiensis's primitive traits are found in early human development. “When you scale things, you get correlated shape variation, and something small might look primitive,” she said.

Jungers calls Weston’s work a “nice, provocative paper” but points out that young mammals have relatively big heads and brains—not at all like those of H. floresiensis. Others remain skeptical of the paper’s methodology, even after delving deep into the Supplemental Information. For example, says John de Vos of Naturalis Museum in Leiden, Netherlands, in comparing the hippo’s brain and body sizes, Weston and Lister used skull volume as a proxy for body size because it was hard to find associated hippo bones. But he was not convinced that the proxy relation holds. Robert D. Martin of the Field Museum in Chicago, Illinois, who has argued that H. floresiensis's brain is too small to have evolved through dwarfing, was also skeptical about whether skull volume can be used to represent body size, noting that if not, the paper’s findings are an “an artifact.” Even if the findings hold up, Martin says, hippos may be a special case, one not necessarily transferable to hobbits.

—Elizabeth Culotta

PHOTO CREDITS: Foot/tibia: William Jungers/ARKENAS; >Hippos: E. Weston, Natural History Museum. Specimens from University Museum of Zoology, Cambridge, U.K.