The honeybee's brain may be small, but the insect has learned to use it to recognize a flower's color and shape as well as to waggle-dance that information back to its hive. In fact, honeybees possess the most complex symbolic language outside of our own family (primates) and they do it with a brain of only one million neurons--five orders of magnitude less than that of humans. More important, this is only four times as many neurons as possessed by fruit flies, flitting creatures that lack any form of society--at least as a bee or human would recognize it. Yet, the newly sequenced genome of the honeybee--Apis mellifera--reveals that some of the same genes that guide the development of a fruit fly's nervous system have been repurposed in the bee to control its genetic ability to switch social roles, among other hive secrets.

George Weinstock of the Baylor College of Medicine's Human Genome Sequencing Center and Gene Robinson of the University of Illinois at Urbana-Champaign led the genome sequencing effort. The job ultimately enlisted 112 scientists at 63 different institutions to help piece together the genetic puzzle of the honeybee, a process that spanned four years. "The honeybee was picked for sequencing because it is a popular system to study social behavior and because of its importance in agriculture through pollination as well as producing honey," Weinstock explains. "Honeybees are the premier pollinator on earth, contributing $10 billion to $20 billion worth of value to our economy," Robinson adds.

The honeybee becomes the fourth insect to have its genome sequenced, following the fruit fly, mosquito and silkworm and preceding a veritable swarm of insect genomes to be revealed in future. Using a large number of drones and one partially inbred queen, the researchers gathered more than three million DNA sequences. After deciphering the sequence composition, a computer helped piece them back together into a nearly complete genetic map--an approach called the whole genome shotgun strategy (also used to sequence the human genome quickly). Much like the human genome, some gaps remain, and the overall gene count is low at this point. "We described about 10,000 genes, about 30 percent less than the fruit fly or mosquito," Weinstock notes. "There are likely other genes to be found that were missed because at 300 million years distance from other [insect] genomes we cannot rely as much on sequence similarity to pick out genes."

Despite diverging from human ancestors more than 600 million years ago, the bee shares a number of genes with its vertebrate cousins that its insect brethren lack, such as those involving RNA interference, aging, DNA methylation and circadian rhythms. "It appears that there were two genes for [circadian rhythm] in the common ancestor," explains genome biologist Kim Worley of Baylor College of Medicine. "The same gene was lost in honeybees and vertebrates, and the other gene was lost in the fruit fly." The honeybee differs from its insect counterparts in a number of other ways as well, including more genes for smell as well as for making use of nectar and pollen, and fewer genes for innate immunity, protective outerwear, detoxification and taste. "They have this mutualistic relationship with flowers: the flowers want them to come and pollinate," Worley notes. "Most plants are putting up toxins for insects that are coming to feed on them. The honeybee didn't develop those defenses." This may help explain another mystery of honeybees: their precipitous decline in recent years. "When they run into other toxins like pesticides, they don't have the repertoire to address them," she adds.

The honeybee genome is already yielding some other surprising conclusions, such as a very slow rate of evolution. "There are fewer changes and substitutions in the honeybee when compared with Drosophila and Anopheles," explains geneticist Martin Beye of the Heinrich-Heine University in Dsseldorf, Germany, but he also notes that the bee has a relatively high rate of exchange of DNA between chromosomes, or recombination, to preserve diversity with only one breeding female in a hive. "The existence of recombination is still one of the major biological questions," he adds. "We can test theoretical predictions on the basis of a 10 times higher recombination rate."

And the honeybee genome has already overturned at least one theoretical prediction: the bee's place of origin. Given that Asia boasts the greatest diversity of bees, ranging from dwarf to giant, many suspected that Apis mellifera began there and spread to Africa and Europe. But tracking mutations--specifically, single nucleotide polymorphisms--entomologist Charles Whitfield of the University of Illinois at Urbana-Champaign has revealed that the honeybee humans know and love originated in Africa. "Certainly the genus itself probably originated in Asia and diversified there," he says. "At some point it got into Africa and then spread back into Europe and Asia." And the genome also proves that a more recent African invasion into the Americas--by the infamous "killer bees"--has proceeded by interbreeding. "Every single bee we looked at in this study was mixed," he notes. "It makes sense that that happened because those honeybees that were first introduced in the Americas were from temperate areas. You introduce this new honeybee from the savanna of Africa, and it is adapted to tropical climates much, much better."

With the genomic map in hand, however, scientists can begin the search for specific genes that control the aggressive behavior exhibited by such Africanized honeybees. More than 50 papers in several journals using the genome are being published concurrently with its revelation in the October 26 Nature. And the ultimate mystery of the hive mind, dictating even down to the level of genetic expression, may eventually be revealed by this work. "My own laboratory is using the genome to help find genes involved in social behavior," Robinson says, "to try to understand the phenomenon of social regulation of gene expression, how social cues act to regulate the activity of genes in the [bee] brain that in turn affect behavior."