Of Fighting Flies, Mice, and Men: Are Some of the Molecular and Neuronal Mechanisms of Aggression Universal in the Animal Kingdom?

Abstract

Aggressive behavior is widespread in the animal kingdom, but the degree of molecular conservation between distantly related species is still unclear. Recent reports suggest that at least some of the molecular mechanisms underlying this complex behavior in flies show remarkable similarities with such mechanisms in mice and even humans. Surprisingly, some aspects of neuronal control of aggression also show remarkable similarity between these distantly related species. We will review these recent findings, address the evolutionary implications, and discuss the potential impact for our understanding of human diseases characterized by excessive aggression.

Fig 1. Evolutionary conservation of molecular and neuronal aggression mechanisms.

A. Transcriptional control module, consisting of conserved transcription factors, co-factors, DNA binding sites, and activated or repressed target genes, regulating development and/or behavior. B. Comparative diagram of the structural relationship of the Drosophila PI and mammalian hypothalamus. C. Simplified evolutionary tree showing the putative conserved transcriptional control mechanism that regulates the release of neuropeptides from the neurosecretory cells in the brain in the regulation of aggression. We postulate that this control module was already present in the bilaterian ancestor (more than 600 million years ago [MYA]) and operates today in extant protostome and deuterostome species (Illustrations courtesy of Josh Rivera). Abbreviations: PI, pars intercerebralis; NSC, neurosecretory cells; SEZ, subesophageal zone; CC, corpora cardiaca; CA, corpora allata.

Fig 2. Human aggression disease interactome.

String analysis of a subset of proteins encoded by disease genes that are characterized by excessive aggression as part of their clinical picture. Roughly 40% of the approximately 90 genes in this category in OMIM form a single network (p = 4.7–10, S1 Table), suggesting that there are mechanistic connections between these components.