“Cracking the Honey Bee’s Genetic Code”
Bee Culture (April 2003), Vol. 131 (4): 19-21
By
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.
Gerontology.
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.
References: