In “Cracking the Honey Bee’s Genetic Code,” Bee Culture, April 2003,¹ I reported that a consortium of scientists and others led by Dr. Gene Robinson at the University of Illinois, Urbana-Champaign had developed a honey bee genome proposal, which was given high priority and had been funded.  Sequencing of the estimated 16,000 genes began December 13, 2002 and was expected to be complete sometime in the Spring of 2003.  After sequencing, the genome will have to be “annotated.”  This lengthy process gives sense to the project by providing information on where the genes are and what they are responsible for.   

Dr. Robinson recently sent me a note stating that the results of both the genome sequencing and analysis are now being published.  He has authored a paper along with Daniel Weaver, current President of the American Beekeeping Federation, characterizing the honey bee genome project (HBGP) as “a model of cooperation between academia, government and industry.”²   The paper further relates that in September 2005, the HBGP shifted to a broader participation by the Consortium, uniting a wide range of scientists in genomics and bioinformatics.  This also included members of diverse disciplinary and organism-based communities, including those studying mammals and humans.  “A total of 112 individuals in 63 institutions around the world signed on to analyze the newly available bee genome sequence!”

 A special issue of the journal Nature,³ one of science’s most prestigious, is due to be published October 26, 2006 featuring the project.  It will contain a major paper on the honey bee genome, as well as specially commissioned commentary.    According to a draft of the paper, “The A. mellifera genome has novel characteristics and provides fascinating insights into honey bee biology.   Some main findings include:

● The honey bee genome is distinguished from other sequenced insect genomes by high AT content, high CpG content, and an absence of most major families of transposons.

● The honey bee genome evolved more slowly than the fruit fly and malaria mosquito.

● The honey bee genome shows greater similarities to vertebrate genomes than Drosophila and Anopheles, for genes involved in circadian rhythms, RNAi, and DNA methylation among others.

● Apis has fewer genes than Drosophila and Anopheles for innate immunity, detoxification enzymes, cuticle-forming proteins, and gustatory receptors, but more genes for odorant receptors, and novel genes for nectar and pollen utilization. This is consistent with honey bee ecology and social organization.

● The major royal jelly protein family, nine genes evolved from one ancient Yellow gene, involved in queen and brood nursing, exemplify genes gaining new functions during the evolution of sociality.

● Novel miRNAs were detected and shown to have caste- and stage-specific expression, suggesting a role in social diversification.

● Key elements in early developmental pathways differ in Apis and Drosophila, indicating that these evolved after the lineages separated.

● The honey bee shows similarities to Drosophila for functions that differ dramatically such as sex determination, brain function, and behavior. 

         ● Population genetic analyses using new genome-based SNPs support a novel hypothesis involving an African origin for the species Apis mellifera and new insights into the spread of Africanized ‘killer’ bees.”

Dr. Robinson and Mr. Weaver in their publication relate that papers are also being published in Science, Proceedings of the National Academy of Sciences, Genome Research, and Insect Molecular Biology.  They further state that it often takes time to translate a genome sequence into major scientific results. However, already tantalizing findings have emerged as listed above, and two, they conclude, are particularly noteworthy at the present time:

1)      “It appears that the honey bee genome evolved more slowly than the genomes of the fruit fly and malaria mosquito. One consequence of that slower evolutionary pace is that the bee genome contains versions of some important mammalian genes that have been lost from the fruit fly and mosquito genomes. Is the honey bee more slowly evolving than most organisms, or have the fly and mosquito (both members of the same order, Diptera) evolved faster?  And if it’s the former, is that because of the bee’s social lifestyle?  These questions can only be answered with genome sequences for more species, and thankfully, more are on the way.

2)      “New population genetic analyses based on the honey bee genome by a team of scientists headed by Charles Whitifield (University of Illinois) have generated exciting new insights into the longstanding controversy of whether Africanized honey bees (Apis scutellata) spread throughout the New World via hybridization or displacement.  The answer is both!  Genes from scutellata have largely replaced many genes from one previously dominant subspecies of European honey bee, Apis mellifera ligustica (the “Italian” bee) while A.mellifera mellifera (the “German black” bee) genes have been essentially unchanged.  It will be fascinating to learn why ligustica and mellifera show different “susceptibilities” to Africanization, and what this might mean for the genetics of defensive behavior, among other things.”

“The HBGP has generated a huge amount of information, and public database development proceeds aggressively to make maximum use of it.  BeeBase is a dedicated analysis and display environment for the honey bee genome, headed by Christine Elsik, Texas A&M University, which will be closely tied to the famous FlyBase and the planned InsectBase (William Gelbart, Harvard University).  Other databases include: NCBI Honey Bee Genomic Resource, ENSEMBL, EBI-Heidelberg, UC Santa Cruz, US-DOE, and the Human Genome Sequencing Center at Baylor College of Medicine (BCM-HGSC).  The BCM-HGSC site also offers the genome sequences for two key honey bee pathogens, Paenibacillus larvae (causative organism of American Foulbrood) and Ascosphaera apis (chalkbrood), projects funded by USDA-ARS (Kate Aronstein and Jay Evans, Principal Investigators).

“In addition to these databases, the honey bee genome will be the exciting frontier for development of a totally new information environment, BeeSpace.  BeeSpace is a $5M project funded by the National Science Foundation’s (NSF) Frontiers in Biological Research Program, headed by Bruce Schatz. (University of Illinois), working together with Robinson.  By integrating the various bee databases with a complete web-navigable catalog of the scientific literature, BeeSpace⁴ will enable information scientists and biologists to leverage the bee genome to create a new information environment for the study of social behavior.  As is the case for the National Institutes’ of Health (NIH) National Human Genome Research Institute (NHGRI) funding, this $5M represents the first funds ever allocated for bee research by this part of the NSF.

“New genomic resources are being created to make best use of the honey bee genome sequence.  These are being developed in collaboration with industry leaders, government labs, and academia, including whole genome microarrays (Viktor Stolc, NASA-Ames; and Robinson, Evans and Kevin White, University of Chicago) and large-scale collections of single nucleotide polymorphisms (SNPs) for European and Africanized honey bees (Whitfield and Baylor College of Medicine).

“Just like the first phase of the human genome project, the HBGP has produced an excellent ‘draft’ of the honey bee genome sequence, enhanced by the detailed genome ‘mapping’ by Solignac and colleagues.  To further increase the value of the honey bee genome sequence to researchers, a white paper to obtain additional sequence information was submitted to NHGRI in July 2005 by a group led by Evans on behalf of the Honey Bee Genome Sequencing Consortium.  The project was again accorded ‘High Priority’ in August, 2005, and this work will begin late in 2006.  The honey bee genome project is expected to usher in a bright era of bee research, for the benefit of agriculture, biological research and human health.”

To reiterate from my April 2003 article, some expected benefits include developments in areas related to:

Novel antibiotics.  Increased drug resistance by pathogenic bacteria has created an urgent demand for new antibiotics. Insects are among the more promising sources of novel antibiotics and honey bees likely offer a rich source because of their sociality. Like humans, honey bees live in a social environment with nearly ideal conditions for growth and transmission of pathogens.

Infectious disease. Humans show both antigen-specific and innate immune responses to important pathogens including Mycobacterium tuberculosis and Streptococcus pneumoniae.  Better understanding of innate immunity can help counter these diseases, especially when vaccines have limited effectiveness.

Bee venom, anaphylaxis and human allergic disease. Honey bees defend their hive aggressively with both sophisticated behavioral and biochemical mechanisms. Bee venom has a wide range of medically important and pharmacologically active compounds.

Nutrition. Honey bees are the premier beneficial insect worldwide. While best known for honey, the honey bee’s more critical contribution to human nutrition is crop pollination, valued at nearly $15 billion/year in the US. Pollination increases the quantity and quality of fruits, nuts, and seeds, many of them increasingly recognized as sources of nutraceuticals. But parasites and pathogens compromise bee health and pollination activities. A HBGP will help to breed bees that resist disease and insecticides, pollinate more efficiently, but sting less. \

Mental health. Some forms of mental illness, such as autism, involve problems with social integration. Bees show a high degree of social integration, and their activities are highly dependent upon their ability to read social cues; identification of several well-defined sets of social cues make for unusually tractable experimental social systems.

Biosensors. A HBGP also may enhance use of honey bees as environmental sentinels.

X chromosome diseases. Mutations on the X-chromosome are responsible for many serious conditions, including Turner's syndrome, Trisomy-X, Kleinfelter's syndrome, hemophilia, colorblindness, and fragile-X syndrome, the leading cause of mental retardation. Honey bees are “haplo-diploid;” in a sense, each bee chromosome is an X-chromosome, i.e., one copy in the male and two copies in the female. A HBGP will enable comparative analyses to address questions such as: What control regions are important in gene expression, sexual development, and dosage compensation on the X? No haplo-diploid animal has yet been sequenced.

 Instincts. The societies of honey bees and other social insects occupy Wilson’s second “pinnacle of social evolution,” with complexity that rivals our own. Among the provocative similarities are: extensive communication systems (including the only non-primate symbolic language); highly organized defense and warfare; complex architecture (including the insect equivalent of skyscrapers – 4 meter high termite nests in Africa); and expressions of personal sacrifice unheard of in most of the rest of the animal kingdom.

Cognition. Bees collect food from flowers, a highly ephemeral food source, and have evolved sophisticated cognitive abilities to maximize foraging success. They are excellent at associative learning, based on the need to associate a color, shape, scent, or location with a food reward. Honey bees also can learn abstract concepts such as "similar" and "dissimilar," and are able to negotiate complex mazes by using visual stimuli as direct or abstract "signposts" or by recognizing path irregularities.

Gerontology. Queens and their workers have identical genotypes but queens live two orders of magnitude longer.  Identification of all differentially expressed genes responsible for these striking differences in lifespan, facilitated by a HBGP, undoubtedly has important implications for human longevity and aging.

The HBGP is exciting not only for new information to come out of the genome itself, but because a wider range of scientists and funding agencies have become interested in honey bees.  This synergy of efforts will enable Apis mellifera to play a greater role as a general research organism, while at the same benefiting the beekeeping community in ways that many believe will be both unexpected and surprising.

References:

1. Bee Culture Articles, <http://www.squidoo.com/Bee_Culture/>, accessed October 21, 2006.

2. Robinson,G. and D. Weaver.  2006.  “The Honey Bee Genome Project:  A Model of Cooperation between Academia, Government and Industry,” American Bee Journal, Vol. 146 (No. 10), pp. 870-872.

3. Wikipedia Open Encyclopedia <http://en.wikipedia.org/wiki/Nature_(journal)>, accessed October 21, 2006.

4. Bee Space Project <http://www.beespace.uiuc.edu/>, accessed October 21, 2006.