image: Hyper-aggressive fruit flies box, albeit without the gloves. Aggressive flies have smaller brain portions and aren't necessarily soothed by mood-altering drugs. view more
Credit: Mark McLawhorn, NC State University
Fruit fly aggression is correlated with smaller brain parts, involves complex interactions between networks of important genes, and often cannot be controlled with mood-altering drugs like lithium.
Those are the results of a painstaking study conducted by researchers at North Carolina State University and colleagues in Belgium who are trying to discover what happens in the genes and brains of hyper-aggressive flies and how that differs from what takes place in more passive fly cousins.
Dr. Trudy Mackay, William Neal Reynolds Distinguished University Professor of Genetics and a co-lead author of a paper published this week in Proceedings of the National Academy of Sciences, says that the findings in the fruit fly could one day lead to helping humans – think of Alzheimer's patients who suddenly become more aggressive – by providing a framework of how complex gene interactions affect behavior. Fruit flies are model organisms for studying genes and traits like aggression.
In the study, the researchers showed that making changes, or mutations, to a handful of genes made some passive flies aggressive and made some aggressive flies really aggressive. They also showed the effects of mating flies with different mutations to see which mutant combinations had larger effects on aggression.
The researchers also showed that certain portions of the fly brain – the so-called mushroom bodies, which affect locomotion, experience and memory – were smaller in the hyper-aggressive flies.
The study also showed that calming did not necessarily come through chemistry, as doses of lithium soothed some but not all of the aggressive flies. These mixed results were also evident when flies were given two other types of calming drugs.
"This study shows that these brain networks are not simple, and that you can't look at just one gene at a time," says study co-author Dr. Robert Anholt, William Neal Reynolds Professor of Biology at NC State.
The researchers measured aggression by watching for fly actions that include, in order from less aggressive to more aggressive: chasing other flies; puffing up their wings in a "wing threat" position; kicking other flies; and, for the roughest flies, standing on their back legs and boxing other flies with front legs.
The study was funded by the National Institutes of Health.
Note to editors: An abstract of the paper follows.
Complex Genetic Architecture of Drosophila Aggressive Behavior
Authors: Michael M. Magwire, Mary Anna Carbone, Robert R.H. Anholt, Trudy F.C. Mackay, North Carolina State University; Liesbeth Zwarts, Marijke Versteven, Liesbet Herteleer, and Patrick Callaerts, Catholic University Leuven and Flemish Institute for Biotechnology
Published: The week of Sept. 26, 2011, in the online version of Proceedings of the National Academy of Sciences.
Abstract: Epistasis and pleiotropy feature prominently in the genetic architecture of quantitative traits but are difficult to assess in outbred populations. We performed a diallel cross among coisogenic Drosophila P-element mutations associated with hyperaggressive behavior and showed extensive epistatic and pleiotropic effects on aggression, brain morphology, and genome-wide transcript abundance in head tissues. Epistatic interactions were often of greater magnitude than homozygous effects, and the topology of epistatic networks varied among these phenotypes. The transcriptional signatures of homozygous and double heterozygous genotypes derived from the six mutations imply a large mutational target for aggressive behavior and point to evolutionarily conserved genetic mechanisms and neural signaling pathways affecting this universal fitness trait.
Journal
Proceedings of the National Academy of Sciences