Top: More zodiacal signs can be seen in the library’s light fixtures and on Heinsbergen’s stenciled ceiling; bottom-left, ringed Saturns grace the lamp chains in the hallways, and bottom-right, the light fixture in Robinson’s vestibule is an armillary sphere—an ancient astronomical tool—
decorated with the signs of the zodiac. Note the compact fluorescent bulb.

From the Birth of Galaxies to the Fate of the Planet

If you have cable TV, chances are during bouts of channel surfing you’ve experienced snippets of something known as the Ultimate Fighting Championship. Literally a no-holds barred contest, two opponents enter the ring—the Octagon, to the initiated—and anything goes until one achieves “submission” over the other. What began as an ethically murky real-life Thunderdome has spawned legions of fans, best-selling books, reality shows, and devoted bloggers.

It would seem the draw of the Octagon has even reached as far as the lab where Caltech scientists led by David Anderson, the Sperry Professor of Biology and a Howard Hughes Medical Institute investigator, use a miniature version (the Octette?) to study aggression in fruit flies. Their recent paper in the Proceedings of the National Academy of Sciences suggests that two distinct inputs—genetic and environmental—converge at a particular gene to shape the decision to fight. The work was done by grad student Liming Wang, the first author of the paper, with Anderson in collaboration with postdoc Heiko Dankert and Professor of Electrical Engineering Pietro Perona.

In the study, male fruit flies were housed either in isolation or in groups of 10. After three days, pairs of flies from each group were placed in a plexiglass arena. The flies raised in isolation fought roughly half of the time, while the socialized flies essentially never fought. The isolated flies, Anderson says, would begin frantically running around and chasing each other when paired up. In stark contrast, the group-housed flies “just sat placidly eating, like cows grazing in a meadow . . . as if they couldn’t care less about their neighbors.”

The scientists repeated the experiment, this time after moving half of the initially isolated flies to a group setting for another three days while keeping the other half in isolation. The still-solitary flies were even more likely to fight, engaging their rivals 80 percent of the time, while their once-aggressive counterparts now rarely fought. This showed that a fly’s level of aggression was both reversible and situational. In other words, the likelihood that a fly would fight depended on its most recent social experience, regardless of its prior circumstances.

Anderson’s group then analyzed the genetic profiles of both sets of flies and identified genes that behaved differently in the isolated and the socialized flies. Comparing this list to one of genes that had been shown by Herman Dierick and Ralph Greenspan of the Neurosciences Institute in San Diego to be associated with aggressiveness, Anderson’s group found one gene on both lists—the unimaginatively named Cyp6a20.

Wang uses a fly aspirator—a piece of tubing with a plastic tip—to transfer the flies from their vials into the arena, the eerily glowing container. Simply point the tip at a fly, inhale gently (a plug prevents you from swallowing the fly), move the tip to where the fly should be, and puff!

This overlap was surprising, given the different methods used by the two labs to generate aggressive flies. The San Diego group bred flies for aggressiveness over dozens of two-week generations, resulting in a stable, hyperaggressive fly lineage. Anderson’s lab focused on social experience, a stimulus measured in days. “We have a common genetic target that acts on different time scales,” Anderson says.

A balance of inherited and environmental inputs makes sense from an evolutionary standpoint. Genes promoting aggression would have obvious benefits in territorial defense and reproductive success; but a mechanism for tempering this innate aggressiveness, for providing situation-specific control of the decision to engage a rival, would also convey an advantage. Sometimes you want to be a lover, not a fighter—the guy who brawls at the slightest drink-sloshing gets bounced from the bar before he can collect very many phone numbers.

Cyp6a20’s precise function in regulating aggressiveness remains a mystery, but Anderson has an intriguing hypothesis. While measuring levels of Cyp6a20 in flies, the researchers found it preferentially in the antennae, the fly’s organ of smell, suggesting it might act in pheromone sensing. Cyp6a20 belongs to a large family of genes that also includes one responsible for converting testosterone to estrogen in vertebrates. The balance between these two hormones has been shown to influence fighting behavior in birds, fish, and mice, and it’s possible that an analogous system is at work in flies.

If pheromones do help control fly aggressiveness, then Anderson believes “the important question is ‘What changes in the brain of the flies that so alters their behavior?’” Socialized flies could be curbing their responses to an aggression-promoting signal, or they could be responding to an aggression-suppressing cue. These two pathways might produce very different patterns of gene activity in individual nerve cells.

So in the end, what do the exploits of a few fruit-fly gladiators mean to the rest of us? The fact that genetics and environment intersect at the seat of a complex behavior like aggressiveness, and that this can occur on the scale of a single gene, gives us a new understanding of just how exquisitely regulated our responses can be. As is so often the case when science delves into the “how” of something, we see that the initial question was overly simple. It’s not nature versus nurture, but how much nature versus how much nurture or, perhaps, when nature versus when nurture. Unmasking the constantly shifting balance of power between the two is far more riveting than anything the Octagon can offer on pay-per-view. —SG