Genetics of Aggression

Abstract

Aggression mediates competition for food, mating partners, and habitats and, among social animals, establishes stable dominance hierarchies. In humans, abnormal aggression is a hallmark of neuropsychiatric disorders and can be elicited by environmental factors acting on an underlying genetic susceptibility. Identifying the genetic architecture that predisposes to aggressive behavior in people is challenging because of difficulties in quantifying the phenotype, genetic heterogeneity, and uncontrolled environmental conditions. Studies on mice have identified single-gene mutations that result in hyperaggression, contingent on genetic background. These studies can be complemented by systems genetics approaches in Drosophila melanogaster, in which mutational analyses together with genome-wide transcript analyses, artificial selection studies, and genome-wide analysis of epistasis have revealed that a large segment of the genome contributes to the manifestation of aggressive behavior with widespread epistatic interactions. Comparative genomic analyses based on the principle of evolutionary conservation are needed to enable a complete dissection of the neurogenetic underpinnings of this universal fitness trait.

Assessment of fight outcome is needed to activate socially driven transcriptional changes in the zebrafish brain

“…Despite the well-known genetic influences on aggressive behavior (4)(5)(6), social status depends to a great extent on group composition (i.e., relative competitive ability of group members) and on social factors, and the same individual must be able to switch between different social statuses (7,8). Hence, the same genotype must accommodate the expression of multiple social phenotypes, and this should be accomplished, at least partially, by socially driven changes in gene expression in the brain that would lead to distinct transcriptome profiles across the social behavior neural network (aka neurogenomic states) (3,9,10) corresponding to status-specific behavioral states.…”

Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior

“…Numerous studies have highlighted the evolutionary conservation of neural pathways affecting aggression (2)(3)(4). Genes affecting bioamine signaling affect aggressive behavior in humans (4,5), mice (6)(7)(8), and Drosophila (9-15).…”

“…Numerous studies have highlighted the evolutionary conservation of neural pathways affecting aggression (2)(3)(4). Genes affecting bioamine signaling affect aggressive behavior in humans (4,5), mice (6)(7)(8), and Drosophila (9-15). The nuclear receptor subfamily 2, group E, member 1 gene Nr2e1 affects aggressive behavior in mice (16) and humans (17,18), and the Drosophila ortholog of murine Nr2e1, tailless, and its transcriptional corepressor, Atrophin, both affect fly aggressive behavior (19).…”

“…The development of reproducible assays for aggressive behavior in Drosophila melanogaster (4,20,21) facilitated the resolution of neural circuits affecting aggression. Neurons expressing the malespecific isoform of the sex-determining gene fruitless (22)(23)(24) are in part responsible for the sexual dimorphism in fighting styles between males and females (25).…”

Exploring a Role for Sleep in Neural Development and Psychiatric Disease

“…Remarkably, even more prolonged mechanical sleep deprivation in mature flies does not cause such long lasting and diffuse impairments, again suggesting a critical role of sleep in development [16]. With the genetic tractability of Drosophila now being employed to tackle even more complex behaviors such as aggression [17], the stage is set to utilize the fly system to examine non-invasively how sleep deprivation and other behaviors are intertwined. A focus on the effect of early sleep disruptions on neurodevelopment, along with exploration of mechanistic underpinnings, is likely to yield tremendous insights into sleep functions during development in both health and disease.…”