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Baylor Buzzing Through Bee Genome; Bug May Yield Secrets of Behavior, X Chromosome Disease

NEW YORK, Jan. 20 - What's inside a bee's brain? The Honeybee Genome Sequencing Project hopes to find out.


Last year, a group of entomologists, geneticists, and beekeepers convinced the National Human Genome Research Institute to pick the honeybee as one of its "high-priority" genomes, putting it first in line for sequencing. Then, in December, Baylor's Human Genome Sequencing Center began running the genome of Apis mellifera through its machines, and is already almost halfway done with the 2.5 million sequence reads the project will probably require.


"It's cranked, and they're going full-bore now," says J. Spencer Johnston, a Texas A&M geneticist who is also part of the consortium.


Predicted to weigh in at about 270 Mb with between 14,000 to 16,000 genes, the bee genome will cost roughly $7 million to complete. Baylor will apply a new technique--clone array-pooled shotgun sequencing--that circumvents the normal fingerprinting process in BAC-based sequencing.


Honeybee BACs are arranged in a set of seven 24x24 pooled arrays, amounting to roughly 4.5x coverage. The team makes a library from each, sequences the libraries, and "deconvolutes" the sequences using some complex calculations in order to reassociate each fragment with the appropriate BAC.


"Suffice it to say that we can get the appropriate sensitivity and specificity to get good sequencing for most of the BACs," Baylor HGSC co-director George Weinstock said in an e-mail.


This technique, according to Weinstock, allows the team to reduce the total number of BAC libraries to be sequenced by 12-fold, from 4,032 to 336. Whole genome-shotgun sequences are then used to increase coverage and help reassemble the genome.


Other consortium members are already working on applications of the sequence data. University of Illinois at Urbana-Champaign entomologist Gene Robinson has developed a cDNA gene chip to explore the neurobiology of this insect's social behavior. Bees have tiny brains but complex behavior, and somehow keep track of an elaborate social world. Robinson's work investigates how gene expression drives bee behavior.


The insects may also shed light on some human disorders. Bees can reproduce through parthenogenesis, in which unfertilized eggs grow into functioning adults --the male drones that do nothing but wait around the hive in the hopes of mating. Female workers have the normal complement of 32 chromosomes, but drones are haploid, and researchers hope that understanding genetic aberrations in this creature may explain how diseases are caused by problems of the X chromosome, which also turns up once in the male and twice in the female.


That peculiarity also makes the drone somewhat easier to sequence, since there's only one allele of each gene, Johnston points out. "We don't have problems with, 'Where did this chromosome come from, the male or the female? Where did it recombine?' We know it all came from the female," he said.


In an unusual twist, the honeybee-sequencing proposal was shepherded by a nonscientist: Texas beekeeper and attorney Danny Weaver, who has a strong interest in molecular biology.


Weaver, who has about 5,000 colonies of bees, comes from a long line of beekeepers, and was able to round up early support from others in the Texas bee industry. His particular interest: improving bee husbandry and identifying SNPs related to bee behavior.


"I've always been interested in moving honeybee research in that direction, and this provides an enormous and wonderful opportunity to move into it," he told GenomeWeb recently. 


Other potential benefits to bee genomics is understanding its pheromone system, how it generates venom, and its commercial value as a crop pollinator and honey producer.


More speculatively, the consortium suggests in its NHGRI proposal that bee genomics could produce new antibiotics: Warm, moist, high-density hives are perfect environments for epidemics, and honeybees presumably have evolved sophisticated immune system techniques to thwart infection. And, since no modern molecular-biology proposal is complete without reference to bioterrorism, the writers also suggest that bees, born explorers, could be trained to serve as biosentinals for chemical and biological weapons.


Baylor plans to have the bee genome sequenced from 6x to 7x coverage within a few months and plans to follow up the project by sequencing the Africanized honeybee.

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