SCIENCE: Fruit fly aggression studies have relevance to humans, animals
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Fruit fly aggression studies have relevance to humans, animals
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Even the tiny, mild-mannered fruit fly can be a little mean sometimes
- especially when there's a choice bit of rotten fruit to fight over.
And, like people, some flies have shorter tempers than others.
Researchers in the North Carolina Sate University genetics department
have identified a suite of genes that affect aggression in the fruit
fly Drosophila melanogaster, pointing to new mechanisms that could
contribute to abnormal aggression in humans and other animals.
The study, led by doctoral student Alexis Edwards in the laboratory of
Dr. Trudy Mackay, William Neal Reynolds Professor of Genetics, appears
online in PloS Genetics.
Feisty flies themselves may not be very scary, but their genes and
biochemistry have more in common with those of humans than the casual
observer might suspect, and geneticists can subject flies to
experiments that simply can't be done on higher organisms.
To measure aggression, the researchers starved male flies for an hour
and a half, then gave them a small food droplet and watched them duke
it out, counting the number of times a focal fly would chase, kick,
box, or flick his wings at other flies.
"Some animals will very vigorously defend their little food patch,
whereas others are relatively polite," Mackay said. "To determine if
this had a genetic basis, we conducted a selection experiment."
For the selection experiment, Edwards pulled three groups of flies -
high aggression, low aggression and control - from the same baseline
population, and kept them separate for 28 generations. From each
generation, she selected the most aggressive flies from the high
aggression group, the least aggressive flies from the low aggression
group, and a random sample of the control flies, to be the parents of
the next generation.
All the flies started at the same level of aggression, but after 28
generations of selection, the high aggression groups were kicking,
chasing and boxing more often, while low aggression groups would hardly
fight at all.
Selection experiments only show these kinds of results when there is
some genetic control over the trait being selected. In this case, the
genetic effect was not very strong - the heritability, or genetic
contribution to, aggressive behavior was about 10 percent. The other 90
percent had to be attributed to environmental variation.
"This is definitely not genetic predeterminism," Mackay said. "It's a
susceptibility. Even in flies, in the constant environment in which we
grow them, the environment is more important than the genes. But we are
very interested in that small genetic contribution."
Next, the researchers wanted to know which specific genes affect a
fly's chances of becoming a bully. To find out, they conducted a
microarray experiment, a way of comparing which genes are turned on or
off, or up or down, in aggressive versus non-aggressive flies.
They found 1,539 genes that were expressed differently in the two
groups - and flies only have about 14,000 genes in all. It will take
more work to find out which of these genes directly affect aggressive
behavior, which ones change as a result of the behavior, and how they
do it.
But Edwards started by studying 19 families of flies, each of which had
a single mutation in one of the genes identified in the microarray
experiment. Fifteen of those 19 mutant families did, in fact, display
abnormal aggression compared to non-mutants, confirming the role of
those specific genes in aggressive behavior.
Those genes were already known to affect nervous system development,
metabolism and immunity, among other things - but none of them had
been previously implicated in aggression. Many of them have human
counterparts.
"Now we have 15 completely novel genes we can use in the future to
investigate aggressive behavior," Mackay said. "Ultimately we hope to
understand the basic biology of this very important trait, because the
better we understand it in flies, the more we can develop logical human
pharmaceutical interventions."
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Note to editors: An abstract of the paper follows.
"Quantitative Genomics of Aggressive Behavior in Drosophila
Melanogaster"
Authors: Alexis C. Edwards, Stephanie M. Rollmann, Theodore J. Morgan
and Trudy F.C. Mackay, North Carolina State University
Published: Sept. 14, 2006, online in PloS Genetics
Abstract: Aggressive behavior is important for animal survival and
reproduction, and excessive aggression is an enormous social and
economic burden for human society. While the role of biogenic amines in
modulating aggressive behavior is well characterized, other genetic
mechanisms affecting this complex behavior remain elusive. Here, we
developed an assay to rapidly quantify aggressive behavior in
Drosophila melanogaster, and generated replicate selection lines with
divergent levels of aggression. The realized heritability of aggressive
behavior was ~ 0.10, and the phenotypic response to selection
specifically affected aggression. We used whole genome expression
analysis to identify 1,539 probe sets with different expression levels
between the selection lines when pooled across replicates, at a false
discovery rate of 0.001. We quantified the aggressive behavior of 19
mutations in candidate genes that were generated in a common coisogenic
background, and identified 15 novel genes affecting aggressive
behavior. Expression profiling of genetically divergent lines is an
effective strategy for identifying genes affecting complex traits.
(Source: North Carolina State University)