Express Yourself

Nomenclature is serious business. Whether you’re an expecting parent, a garage rocker immortalizing your latest trio, or an astronomer pondering a mass of orbiting ice, the names you choose symbolize ideals. And so the child’s name evokes a poet, the band’s provokes convention, and the asteroid, why, it becomes an homage to a Grecian deity. Naming the name arouses a sense of mission.

Now consider this: one-eyed pinhead. Quite a bit of work and life experience went into that particular moniker. It turns out that a graduate student in the lab of geneticist Christiane Nüsslein-Volhard at the University of Tübingen in Germany, had discovered in zebrafish that a particular gene, when mutated, causes a rare developmental disorder in which the embryo fails to divide the eye orbits into two cavities, resulting in a single eye.

Revenge Served Cold

 In the world of genetics, when you discover a gene’s function, you name it. Consider it a perk. Since zebrafish and fruit fly researchers typically name a gene after the phenotype its mutant spawns, calling it “one-eyed” preserved tradition. This particular student, however, was also going through a nasty breakup with her boyfriend. And so, as an eternal dig to the man who broke her heart, the gene was christened one-eyed pinhead.

Welcome to the world of gene naming: two parts science, one part acrid wit. Right now, you carry a gene named after a researcher surnamed Harvey (HRAS), another named after a retro video game (sonic hedgehog), and yet another named after a grad student’s dog (warthog).

“Most scientists are vain,” says Spyros Artavanis-Tsakonas, an HMS professor of cell biology, “and naming things is one manifestation of our vanity. It’s how we make our mark, while having some fun!”

But according to Clifford Tabin, the George Jacob and Jacqueline Hazel Leder Professor of Genetics and head of the School’s genetics department, such a tradition has practical benefits as well. “These names are visual, and you remember them,” he says. “If you name a gene X47326.7, who’s going to remember that?”

Not everyone shares Tabin’s enthusiasm. The HUGO Gene Nomenclature Committee, which works under the auspices of the Human Genome Organisation, based in Cambridge, England, is determined to scrub the literature of potentially inappropriate names. For HUGO’s members, it’s a question of acknowledging patients’ sensitivities: No one wants to hear that they bear a warthog gene. Tabin, in fact, tops the group’s most-wanted list of offending namers. In addition to bestowing a fruit fly gene with the name sonic hedgehog, his lab is responsible for the Drosophila genes Indian hedgehog, desert hedgehog, radical fringe, and lunatic fringe—each of which HUGO has directly targeted.

Family Ties

The hedgehog genes are part of a larger family of genes involved in embryonic development. In the larvae–maggot stage, fruit flies have bristles on their proto-limbs that aid mobility. The bristles tend to be organized in rows, not unlike bristles on a toothbrush. Genes that affect this bristle patterning were named after spiny mammals, not only the hedgehog but also the armadillo and the porcupine. Other mutations that blocked bristle growth altogether ended up with such handles as naked and—borderline creepy—shaven baby.

In the early 1990s, Tabin’s lab discovered three subtypes of the hedgehoggenes. Rather than simply cataloging the genes numerically, they decided to name them after different hedgehog species. And so the first was dubbed desert hedgehog, and the second Indian hedgehog. The researchers had referred to a third subtype as European hedgehog. One of Tabin’s postdocs, however, had a young daughter who had just been given a Sonic the Hedgehog comic book for her birthday. At that time, Sonic the Hedgehog was a character introduced in the eponymous video game developed by the Japanese software giant Sega. The postdoc, who was also a musician on the side, fell in love with the name. So, when the paper was finally submitted, “European” was out, and “sonic” was in.

Could You Repeat That?

Yes, it’s that easy. When it comes to claiming your gene, it’s less like filing a patent and more like naming a pet. Find a title that’s both scientifically and aesthetically pleasing, document it in your published finding, and then, through an unspoken pact, the name gets fixed. Researchers who subsequently stumble upon the same gene in other species maintain the original birth name: What starts in the fly continues to the human. With each published paper, the name becomes more firmly established. If you think this tradition renders HUGO’s efforts quixotic, you could be right.

“We always respect the first precedent and stick to the name,” says David Van Vactor, an HMS professor of cell biology, who has discovered quite a few fruit fly genes, bestowing them with names such as stranded, shortstop, beaten path, bypass, and walkabout.

Van Vactor came up with walkabout while a postdoctoral researcher at the University of California, Berkeley, working with an Australian scientist. It is a gene whose mutant form causes motor neurons to miss their targets and, hence, to wander at will. Another was identified by a colleague of Van Vactor’s who was from the United Kingdom and thus accustomed to the directional miscues of traffic circles. He named his gene roundabout. Yet another gene, one Van Vactor characterized while he was a student, enables membranes in a fly’s photoreceptors to form perfect crystalline arrays of microvilli. When mutated, these same arrays descend into chaos, thus, the gene became chaoptic.

If you think that sounds like a good name for a rock band, Van Vactor agrees. “I’ve been struck by the naming of bands over the years,” he says, “and I think these mutants provide a lot of grist for that mill.”

Toll Story

Yet while names like hedgehog and walkabout are decidedly descriptive, other names are assigned under far more random and serendipitous circumstances.

For example, Toll genes, first identified more than 20 years ago, encompass a class of embryogenic molecules that were eventually found to contribute to a fly’s immunity to fungal infections. The researcher who first identified the mutant variants of Toll was German. Legend has it that when she first observed the mutant phenotypes, she shouted, “Amazing!” But her cry was in German, and, in that language, “amazing” becomes “toll.”

Currently, Artavanis-Tsakonas and his lab are examining a particular gene that has revealed some interesting phenotypes. He is pretty sure that the gene will ultimately be named hori. The postdoctoral student leading this research applauds that idea. That postdoc’s name? Hori.

A Fly in the Ointment

Things aren’t quite so freewheeling in the world of worms, where the nematode Caenorhabditis elegans is the predominant model. Nomenclature for worm genes follows more of a card-catalog process. No funny stuff here. All names are based on a classification system inspired by bacterial genetics. Genes that affect lineage, for example, are prefixed by “lin-” followed by a number designating the order of discovery. Currently, lin genes number lin-1 through lin-66, and those in between are neither sonic nor shaven.

“The nomenclature for worm genes is really logical,” says Gary Ruvkun, an HMS professor of genetics at Massachusetts General Hospital and arguably one of the world’s foremost experts on worm genomics, “and quite a disaster for anyone outside of the field. It is a system of mathematical precision but mnemonic catastrophe.”

Such systematized taxonomy belies the personality of the father of C. elegans genetics, Nobel laureate Sydney Brenner, a man reputed for his wicked sense of humor.

Maybe this is an accident of history. Brenner’s research achieved prominence during the 1960s, when computerization was on the rise, and a more orderly and less cheeky approach may have been more fashionable. Compare that with the origins of fruit fly genetics, which can be traced back to Thomas Hunt Morgan’s fly room at Columbia University in the early 20th century. In Morgan’s era, embryology was all the rage, so that’s where all the cool kids went, leaving the “different drummer” types to fly genetics.

“The people who gathered around Morgan were considered pretty weird in their day,” says Artavanis-Tsakonas, a proud descendant. “They were very smart, but they were the outcasts. So a certain sociological gestalt developed. That tradition has held for a long time.”

But while Ruvkun admits that, as a worm geneticist, he wishes he had such a vehicle for laughs, he cautions that “the fruit fly gene-naming freedom, while memorable, can be disruptive.” Examples that immediately come to mind for him are I’m not dead yet (abbreviated as Indy) and Ken and Barbie(describing mutations that remove sex organs).

“In the end,” Ruvkun adds, “I think that a naming convention that is not as circumscribed as C. elegans and not as self-consciously cute as Drosophilawould work best.”

But the name game has only just begun. While the Human Genome Project has identified roughly 20,000 human genes, many of them have yet to be characterized. And those 20,000 are just genes for protein-coding sequences. DNA codes for a whole lot more than that (microRNAs, anyone?) and so the potential for creativity is as dynamic as ever.

“It’s like the dotcom-naming domain,” says Van Vactor. “There are quite a few empty slots still out there.”