Johns
Hopkins scientists report what is believed to be the first evidence
that complex, reversible behavioral patterns in bees—and presumably
other animals—are linked to reversible chemical tags on genes.
The
scientists say what is most significant about the new study, described
online September 16 in Nature Neuroscience, is that for the first time
DNA methylation “tagging” has been linked to something at the behavioral
level of a whole organism. On top of that, they say, the behavior in
question, and its corresponding molecular changes, are reversible, which
has important implications for human health.
According
to Andy Feinberg, M.D., M.P.H., Gilman scholar, professor of molecular
medicine and director of the Center for Epigenetics at Hopkins’
Institute for Basic Biomedical Sciences, the addition of DNA methylation
to genes has long been shown to play an important role in regulating
gene activity in changing biological systems, like fate determination in
stem cells or the creation of cancer cells. Curious about how
epigenetics might contribute to behavior, he and his team studied a
tried-and-true model of animal behavior: bees.
Working
with bee expert Gro Amdam, Ph.D., associate professor of life sciences
at Arizona State University and the Norwegian University of Life
Sciences, Feinberg’s epigenetics team found significant differences in
DNA methylation patterns in bees that have identical genetic sequences
but vastly different behavioral patterns.
Employing
a method that allows the researchers to analyze the whole genome at
once, dubbed CHARM (comprehensive high-throughput arrays for relative
methylation), the team analyzed the location of DNA methylations in the
brains of worker bees of two different “professions.” All worker bees
are female and, within a given hive, are all genetically identical
sisters. However, they don’t all do the same thing; some nurse and some
forage.
Nurses
are generally younger and remain in the hive to take care of the queen
and her larvae. When nurses mature, they become foragers that leave the
hive to gather pollen and other supplies for the hive. “Genes themselves
weren’t going to tell us what is responsible for the two types of
behavior,” Feinberg says. “But epigenetics—and how it controls
genes—could.”
Feinberg
and Amdam started their experiment with new hives populated by bees of
the same age. That removed the possibility that any differences they
might find could be attributed to differences of age. “When young,
age-matched bees enter a new hive, they divvy up their tasks so that the
right proportion becomes nurses and foragers,” explains Amdam. It is
these two populations that were tested after painstakingly
characterizing and marking each bee with its “professional,” or
behavioral, category.
Analyzing
the patterns of DNA methylation in the brains of 21 nurses and 21
foragers, the team found 155 regions of DNA that had different tag
patterns in the two types of bees. The genes associated with the
methylation differences were mostly regulatory genes known to affect the
status of other genes. “Gene sequences without these tags are like
roads without stop lights—gridlock,” says Feinberg.
Once
they knew differences existed, they could take the next step to
determine if they were permanent. “When there are too few nurses, the
foragers can step in and take their places, reverting to their former
practices,” says Amdam. The researchers used this strategy to see
whether foraging bees would maintain their foraging genetic tags when
forced to start acting like nurses again. So they removed all of the
nurses from their hives and waited several weeks for the hive to restore
balance.
That
done, the team again looked for differences in DNA methylation
patterns, this time between foragers that remained foragers and those
that became nurses. One hundred and seven DNA regions showed different
tags between the foragers and the reverted nurses, suggesting that the
epigenetic marks were not permanent but reversible and connected to the
bees’ behavior and the facts of life in the hive.
Dramatically,
Feinberg noted, more than half of those regions had already been
identified among the 155 regions that change when nurses mature into
foragers. These 57 regions are likely at the heart of the different
behaviors exhibited by nurses and foragers, says Amdam. “It’s like one
of those pictures that portray two different images depending on your
angle of view,” she says. “The bee genome contains images of both nurses
and foragers. The tags on the DNA give the brain its coordinates so
that it knows what kind of behavior to project.”
The
researchers say they hope their results may begin to shed light on
complex behavioral issues in humans, such as learning, memory, stress
response and mood disorders, which all involve interactions between
genetic and epigenetic components similar to those in the study. A
person’s underlying genetic sequence is acted upon by epigenetic tags,
which may be affected by external cues to change in ways that create
stable—but reversible—behavioral patterns.
Authors
on the paper include Brian Herb, Kasper Hansen, Martin Aryee, Ben
Langmead, Rafael Irizarry and Andrew Feinberg from The Johns Hopkins
University, and Florian Wolschin and Gro Amdam of the Norwegian
University of Life Sciences and Arizona State University.
This
work was funded through the NIH Director’s Pioneer Award through the
National Institute of Environmental Health Sciences (#DP1ES022579), the
Research Council of Norway and the Pew Charitable Trust.
Reversible switching between epigenetic states in honeybee behavioral subcastes
Source: Johns Hopkins Medicine