Genetic links illuminate bee social life

How social life evolved from solitary ancestral lifestyles has been an enduring mystery for years, and now scientists are one step closer to unraveling its genetic underpinnings.

In a paper published in the Public Library of Science journal PLoS Biology, ASU School of Life Sciences (SoLS) collaborators Gro Amdam, Robert Page and Kate Ihle, together with University of California-affiliated researcher Mindy Nelson, have shown that a single gene, vitellogenin, controls multiple aspects of honey bee social organization. (Read the full article here.)

Vitellogenin encodes for the protein vitellogenin, which is found in most egg-laying organisms (there is even a homologous gene family in humans). It was first discovered in honeybees in the 1970s. That queen bees expressed the protein came as no surprise, as they are the dominant egg layers in a hive. But the fact that the protein also was found in the essentially sterile female worker bees caught scientists’ interest.

However, since no role for it in workers could be found at the time, some speculated that it was simply evolutionary “baggage.” One of those who didn’t agree was Amdam.

“I came out of a mathematical background, with emphasis on theoretical regulatory biology,” Amdam says. “The models I built on vitellogenin dynamics suggested that worker bees synthesized large amounts per time unit, and since the protein did not accumulate in tissues and blood, it was likely metabolized or transferred somewhere else.”

In 2002, while Amdam pursued her doctorate at the Norwegian University of Life Science, she discovered where that “somewhere else” was. Vitellogenin produced in workers was fed to queens and bee larvae as “royal jelly.” Thus, a protein believed to be exclusively linked to egg development had changed its job description in sterile bees.

“This was achieved by workers expressing an ovarian vitellogenin receptor on their paired head glands, which are responsible for the making of jelly,” she says.

Worker honeybees go through a sequence of tasks as they age. They start out as nest workers that produce jelly, and later turn to foraging for nectar and pollen in the field. Foragers do not produce vitellogenin. The insight that vitellogenin was important during the nest stage, and thus for worker division of labor, led Amdam to speculate that the protein could – directly or indirectly – affect the bees transition from nest tasks to foraging duties.

“The age at onset of foraging is highly variable, but there was no good physiological model for explaining this variation,” Amdam says. “One possibility was that the probability of starting foraging was related to the level of the bees’ dynamic vitellogenin stores. This would ensure that vitellogenin-rich bees stayed in the nest as useful nurses of the brood and other bees, whereas vitellogenin-exhausted bees became foragers.”

In a first attempt to address this hypothesis, Amdam and colleagues at the University of Saõ Paulo showed that suppression of vitellogenin leads to high titers of juvenile hormone – a systemic hormone associated with foraging activity.

Parallel experiments by Amdam’s group in Norway further suggested that vitellogenin could scavenge free radicals and possibly and extend lifespan by reducing oxidative stress damage to workers and queens.

Amdam’s curiosity about the switch between nursing to foraging led her to collaborate with Page, who studied the division of labor between nectar and pollen foraging bees. Page’s selection program had resulted in honeybee strains that had different foraging preference: one strain preferred nectar, the other pollen. These strains also differed with regard to the average age of foraging onset.

Amdam and Page started to map out their vitellogenin dynamics, first at the University of California-Davis, then at ASU, when Page became director of the School of Life Sciences. Amdam came to the College of Liberal Arts and Sciences as a SoLS assistant professor in 2005.

“This collaborative work was all very exciting,” Amdam says. “Rob and I confirmed that vitellogenin was possibly involved in division of labor (nurse versus forager); possibly involved in further division of labor between foragers (as nurse bee pollen specialists have higher vitellogenin levels than future nectar specialists); and possibly affecting the lifespan of workers. These are very central aspects of a worker bee’s life history – addressing how they mature and develop behaviorally in the colony, the way they divide labor among them, and how long they live.”

The direct linkage between these three aspects of social life histories in bees and the gene, vitellogenin, was solidified in the study published in PLoS Biology through the use of RNA interference.

RNA interference (RNAi) is a gene-silencing tool that can specifically “knock down” a target gene. It was first created by researchers Andrew Fire and Craig Mello, who were awarded a Noble Prize in 2006 for its development. Amdam was the first to adapt this technique for use in adult honey bees and to target vitellogenin. In the study, vitellogenin knockdowns are shown to initiate foraging earlier in life, to show a preference for nectar collection and die more quickly than in control animals.

According to Amdam, all three hypotheses were confirmed in this study.

“We now know that vitellogenin paces the behavioral development of bees,” she says. “It is part of the machinery that determines when they start foraging. It is a primer for the bees subsequent preference for nectar or pollen.”

Ihle, a graduate student in Amdam’s and Page’s laboratories and a collaborator on this paper, adds that RNAi will give them the opportunity to use functional genomics to investigate the overall origins of sociality.

Amdam agrees.

“Our work with vitellogenin shows that many of the highly derived social behaviors that people tend to think might be new or novel actually build on the exploitation of a very old gene that is present in reproductive, solitary foremothers,” she says.