May 16, 2005|
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May 16, 2005 |
Fruit fly experts known for pop culture prowess By Stacey Singer When that task fell to Steve Kay, a cell biology professor at The Scripps Research Institute, he pondered the gravity of naming rights. He considered that scientists years later still would be using his term. Then he accepted the suggestion of his partner, Jeff Hall, of Brandeis University. "We called it cry baby because it was one of Jeff's favorite Janis Joplin records," Kay said. The gene they found spells out instructions for a fruit fly protein called cryptochrome. The first three letters spell CRY, Kay explains, so the name made some sense, chemically speaking. It also added a bit of whimsy to serious scientific research. Consider the case of sonic hedgehog, named after a video game character. Scientists use model organisms like mice and nematodes to understand more complex animals. There are entire groups that focus exclusively on fruit flies, and fruit fly geneticists are fond of pulling references from popular culture. They typically name a gene based on the appearance or behavior of the fly born with the mutation. It has resulted in groucho (bushy), cheapdate (sensitive to alcohol), sozzled (unsteady on its feet), tinman (needed for heart development; think Wizard of Oz). Hedgehog, a bristly looking gene, reminded its discoverers of Sonic the Hedgehog, the video game character. The name stuck even after the gene's unfuzzy importance to humans was realized. Human geneticists, considered more of a strictly-business bunch, tend to name genes according to their chemistry or association to disease. They prefer to call genes by their symbols, such as BRCA3, for breast cancer 3, and CFTR, for cystic fibrosis. Informative, but not as much fun. Those wacky fly geneticists often have the last laugh. Because flies mate quickly, fly geneticists have beaten the human scientists to naming rights for many genes common to both the insects and people. The human-gene club has been left with little choice but to use some of these names. The result is oddball constructions like hedgehog acyltransferase. In flies, the hedgehog gene name made sense: Its spiky little flies resemble the porcupine-like animals common to British gardens. The gene's human relatives, however, have little to do with bristles. Sonic hedgehog makes a protein that sculpts human embryos' nervous system, limbs and organs. Later in life, it can activate hair growth and contribute to several types of cancer. It's hugely interesting to stem cell scientists and oncologists. But the Norwegian scientist who discovered sonic hedgehog 12 years ago now regrets that it's named after a SEGA video game. He allowed his American collaborators to talk him into adding sonic to the name. The hedgehog part had been decided years before by the irreverent fruit fly scientists. "I do not really like such pompous names, and I did not know any computer game characters," Stefan Krauss, now at the Norwegian Center for Stem Cell Research, wrote in an e-mail. "But everybody was just getting out of control in those days." Indeed, when new technology allowed the fruit fly genome to be sequenced in 1998, the 50 scientists who first tried to make sense of the results called the meeting a jamboree. Thanks to the new sequencing technology and advanced computer algorithms, genes they had sought for years appeared before their eyes. They found genes for color vision and smell, brain development and insulin regulation, all in a few days. Their energy and excitement was described in James Shreeves' book The Genome War. But when it comes to naming new discoveries, conservatism is slowly winning. A London-based group called the Human Gene Nomenclature Committee, part of the Human Genome Organisation, has been working hard to contain some of the exuberance of those early days. The group has developed elaborate gene-naming guidelines that now require a symbol of three or four letters and possibly a number. Their searchable database links to other species' databases and shows other ways of identifying the genes, by code. "We can't have them naming genes for their pets and so on," said Conover Talbot Jr., a Johns Hopkins University bioinformatics professor who is the only U.S.-based member of the nomenclature committee. The group has obtained veto power over gene names by gaining the confidence of the major scientific journals. Nature requires approval from the nomenclature committee before it will publish an article on any new genes, said Chris Gunter, the journal's genetics and genomics editor. "For human and mouse genes, it has to have three or four letters and sometimes one number," she said. Added Talbot: "It creates a tower of Babel if everybody gets to name his or her own gene his or her own way." Even with those constraints, some dedicated scientists have managed to continue slipping creative names past the group. The KISS-1 gene managed to squeak past, but not without a fight, said Dan Welch, a pathology professor at the University of Alabama at Birmingham School of Medicine. He refers to the nomenclature committee as "the people who always want to change your gene names." At the time he discovered the KISS-1 gene, he was working at the Penn State College of Medicine in Hershey, Pa., home of the famous chocolate maker. At a colleague's suggestion, he intentionally named it KISS to remind people of Hershey's place in its discovery, and to jog memories. "If you get people to remember it, that's the most important thing," Welch said. Welch said he's glad he fought to retain the KISS-1 name. As more scientists study its effects, they're glad, too. It has public relations value. A University of Pittsburgh Medical Center news release recently announced the gene's effect on puberty this way: "A gene's first 'kiss' sets off that affair known as puberty." Welch liked it. "Marketing is definitely important," he said. Talbot's not opposed to a bit of marketing but not at the expense of clarity. As long as people adhere to the system, he said, they can give genes whatever nicknames they want. Searchable databases will do the rest. And so if you go to www.gene.ucl.ac.uk/nomenclature/ and type in the name sonic hedgehog, you'll see that the approved symbol is SHH, that its approved full name is "sonic hedgehog homolog (Drosophila)" and that it's catalogued differently in five other databases. You also can find it on the fruit fly database, flybase.bio.indiana.edu/. It's not quite as orderly as Linnean Latin, but it's a start. Three centuries ago, Swedish botanist Carl Linneaus called on his fellow scientists to be systematic about the naming of their discoveries. What was required, he argued, was a language and an organizational system that could be understood throughout the world. He chose Latin because it was the universal language of science at the time. He suggested descriptive genus and species names that revealed something about the shapes of the leaves or the kind of soil a plant preferred. Occasionally, he would honor a great scholar with a Latin version of his name. Talbot thinks about similar descriptive goals when considering proposed gene names. He regrets some names that have gotten past the nomenclature committee: RING, short for "Really Interesting New Gene," for example. It says little about the gene's function. The nomenclature committee's desires are the same now as Linneaus' were 300 years ago to bring order to a chaotic system. "The goal is to have it be meaningful," Talbot said. "If we do our job, we make it easier for other people. In truth, sonic hedgehog in humans isn't descriptive." As the era of gene discovery matures, some fear that most of the important genes have been discovered and named. Talbot says that's not the case. "I don't think we're going to be out of jobs in the near future," he said. "We're still finding things out about the sequence."
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