“Cracking the Honey Bee’s Genetic Code”
Bee Culture (April 2003), Vol. 131 (4): 19-21
Dr. Malcolm T. Sanford
One cannot escape ubiquitous
references to DNA in today’s information age.
These three letters are everywhere and the substance they stand for is
touted to be responsible for everything from determining the remains of long
lost relatives to solving crimes.
Perhaps the most significant effect of DNA analysis so far is the release
of all prisoners on death row in
DNA stands for the chemical compound deoxyribonucleic acid. The structure of DNA was first described in 1953 by James Watson and Francis Crick in the Journal Nature.3 They characterized the structure as a double helix; two paired strands held together by four specific molecules, called paired bases. The paired bases are like stair steps that are enclosed in a spiraling staircase molecule. DNA is not only a molecule, it also is information because the order or sequence in which the bases are found determine how organisms produce proteins from the body’s building blocks called amino acids.4 Another way of looking at this is that the paired bases are letters making up sentences that in their entirety is the language for how an organism operates, its genetic code.
Ever since language arose, humans have been involved in cracking code, determining the real meaning of first symbols and then words. Perhaps the most dramatic examples are those associated with World War II. The allies coming into possession of the German code books gave them a great advantage in winning the conflict. In the pacific, “code talkers” were employed. Since the Japanese could listen to radios and find out what English-speaking troops were planning, Navajo-speaking American Indians were employed to send messages back and forth. Perhaps the most famous code up until now was that developed by Morse that drove the telegraph before voice could be transmitted through wires.5
With discovery of the structure of the informational molecule DNA, the genetic code of organisms, indeed all of life on planet earth, can now be cracked. This is a huge task, but is becoming easier with the development of powerful digital computers. Recently the human code, called the genome, was deciphered in total, some 3 billion base pairs or letters.6 Others on the fast track include the chicken (Gallus gallus), chimpanzee (Pan troglodytes), dog (Canis familiaris) and kangaroo (Macropus species). Insects are also on list including the silkworm (Bombyx mori) and the honey bee (Apis mellifera).8
A consortium of scientists and others led by Dr. Gene Robinson at the University of Illinois, Urbana-Champaign has developed a honey bee genome proposal, which was given high priority and has been funded .9 Sequencing of the estimated 16,000 genes began December 13, 2002 and is expected to be complete sometime in the Spring of 2003. The trace archive shows the raw information as it is submitted to the National Center for Biotechnology Information.10 Dr. Jay Evans, who just was nominated "Outstanding Early Career Scientist of 2002" by the Agricultural Research Service (ARS), the chief scientific research agency of the U.S. Department of Agriculture, heads up the Beenome World Wide web home page, which has the goal of summarizing and presenting new genetic data from honey bees in a timely fashion.11
This is not a trivial pursuit. The Consortium estimates it will take four months and cost $7 million, involving 350 laboratories and 1500 scientists. The results of this project are expected to be substantial in terms of both human and insect health. In addition, this is the first social organism to be sequenced and special benefits are expected from this particular situation.
The proposal says, “Homo sapiens (humanity) is a highly social species and social interactions are critical determinants of human mental and physical health. We propose to sequence the genome of another highly social species, the honey bee, Apis mellifera. Though phylogenetically distant, honey bees live in societies that rival our own in complexity, internal cohesion, and success in dealing with the myriad challenges posed by social life, including those related to communication, aging, social dysfunction and infectious disease. A honey bee genome sequencing project (HBGP) will benefit human health and medicine in diverse areas, including venom toxicology, allergic disease, mental illness, infectious disease, parasitology and gerontology. In addition, the HBGP will improve human nutrition by enabling enhanced pollination of food plants and accelerated delivery of hymenopteran parasitoids for biological control of pests. The HBGP will also improve honey bee sentinel function, providing enhanced capabilities for detection and location of chemical and biological agents of harm. Sequencing the genome of the honey bee, a beneficial, non-dipteran, insect endowed with a small brain but cognitive sophistication, with complex social organization but amenable to molecular, genetic, neural, and ecological manipulation, will provide important tools and unique models to improve human health. When these benefits are balanced against the costs of sequencing a 270MB genome, the HBGP promises to provide a valuable and economical resource.”
Specifically, the Consortium expects the following areas to benefit from the HBGP (edited by this author but mostly in the words of those who wrote the proposal):
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. Food is constantly shared among individuals, the beehive is maintained at a temperature of 33ºC (93ºF) and 95% relative humidity, and population densities are mind-boggling (as many as 50,000 adults and 50,000 juveniles at densities equivalent to ca. 15 adult humans in a 6 x 4 m apartment). Although afflicted with many diseases, honey bees must have evolved many powerful antibacterial peptides to cope with the huge number of pathogens that would thrive in such conditions. Interest in this topic is increasing, but a HBGP is necessary for efficient genomic bio-prospecting.
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. Non-human models, especially insects, are very useful; immunity is phylogenetically ancient, and defensive strategies are highly conserved at the molecular level. “Community genomics” promises to provide new epidemiological and mechanistic insights into human infectious diseases. A HBGP also will provide information on parasite resistance, as the DNA source for the HBGP is a strain resistant to Varroa destructor, a serious bee parasite. This selected bee strain suppresses Varroa reproduction via as yet unknown mechanisms.
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. Several of them already have been identified, notably melittin and apamin, with outstanding therapeutic potential for cancer, sleep disorders, learning and memory enhancement, Parkinson’s disease, HIV and AIDS associated dementia, schizophrenia, and novel non-viral vector development for gene therapy. But other venom components remain to be identified. Because honey bees have had intense evolutionary pressure from mammalian predators, it is likely that bee venom contains other compounds with similar human therapeutic potential.
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
Mental health. Some forms of mental illness, such as autism, involve problems with social integration. The basics of how individuals respond to their social environment (sensory structures, signal transduction cascades, various forms of neural plasticity) are highly conserved across phyla. 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. Combined with a HBGP and the highest known genetic recombination rate of any animal, this provides the platform for mapping complex behavioral traits, including those related to social integration.
Biosensors. A HBGP also may enhance use of honey bees as environmental sentinels. Honey bees evolved as efficient explorers, canvassing and exploiting areas of several square miles around their hive. As such, honey bees function as a comprehensive array of autonomous biosensors, capable of reporting the presence, location and concentration of environmental toxins. Preliminary evidence suggests bees can be trained to locate substances used in various types of warfare, and bees have been deployed in ongoing DARPA research to detect biological and chemical weapons. These security-related activities might be aided by “tuning” bee detection capabilities with information obtained from the identification of genes involved in olfaction, e.g., olfactory receptor genes, which are very difficult to find without extensive genome sequence information due to rapid evolutionary sequence divergence.
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. These are thought to be due in part to unique features of X chromosome biology, among them the demands of dosage compensation and sex determination. 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? What role, if any, do orthologs of dosage compensation and DNA repair genes play in a haplo-diploid? No haplo-diploid animal has yet been sequenced.
Instincts. The societies of
honey bees and other social insects occupy
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.
Other areas include determining gene regulation, providing a better connection between human and non-human genetic sequences, and expanding understanding of developmental biology, neurobiology, and complex systems analysis.
Finally, there is the possibility of better understanding evolutionary processes. As the Consortium concludes in its document: “Altruism is the social glue, the trait that enables a complex society to evolve and function. But altruism has long been an evolutionary enigma, inconsistent with basic Darwinian theory. This is seen in its starkest form in the insect societies: Most members spend their lives helping the queen to reproduce rather than increase their direct fitness by generating their own progeny. Efforts to solve this puzzle have had profound effects. They have led to the development of many of the most widely accepted theories of social evolution in all organisms, including humans, i.e., kin selection and reciprocal altruism, and have spawned ‘evolutionary psychology,’ a controversial subdiscipline that assumes that aspects of human sociality are evolved traits, and therefore have biological bases. Molecular analyses of bee social behavior can contribute to our understanding of social evolution. While ants and termites are all highly social, there are bee species that span the range of possible social phenotypes from solitary to primitively social and on up to those with the most advanced societies. In addition, within the Order Hymenoptera (ants, bees, and wasps), it is estimated that sociality evolved independently at least 11 times. A comparative genomic approach, spearheaded by a HBGP, can use these natural experiments to gain insights into the molecular basis of sociality.”
Given the points made above about the benefits, it is easy to see why many in both the beekeeping and lay community await the results of Honey Bee Genome Sequencing Project with great enthusiasm. Some of this must be tempered, however, with the knowledge that the honey bee has often proven to be an enigma to beekeepers who would attempt to manage such a complex, social insect. It is suggested, therefore, that we humans in an effort to crack the honey bee’s genetic code do so with a good deal more humility than hubris.