Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Abstract

Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary "toolkits"-genes and modules with lineage-specific variations but deep conservation of function-participate in the behavioral response to social challenge. Here, we develop a multispecies computational-experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA-seq profiling in three diverged species-honey bees, mice and three-spined stickleback fish-following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G-protein-coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems-level mechanisms that have been repeatedly co-opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes.

Oxytocin, Dopamine, and Opioid Interactions Underlying Pair Bonding: Highlighting a Potential Role for Microglia

“…The molecular toolkit hypothesis posits that a handful of neuromodulatory systems underlie social behavior across species ( 67 , 158-161 ). To date, explanations for how these systems mediate species differences in social behavior have investigated differences in receptor patterning or ligand production/release.…”

Comparative genomics identifies putative signatures of sociality in spiders

“…Previous studies in social insects (ants and bees) identified expansions of gene families associated with metabolism and chemical communication functions (Simola et al 2013;McKenzie et al 2016;Wurm et al 2011;Kapheim et al 2015). Similarly, previous comparative studies across animals have emphasized genes associated with metabolism as being important in the response to social challenges (Rittschof et al 2014;Saul et al 2019), suggesting that changes in genes with metabolic functions might often be involved in social evolution across animals. Indeed, previous research indicates that social spiders may have lower metabolic rates than their solitary relatives (Zimmerman 2007), further implicating changes in metabolic-related genes to the evolution of social life in spiders.…”

Consideration of genetic and sex effects in mice enhances consilience with human addiction studies

“…Behavioral genetics in non-human animals aims to establish consilience with psychiatrically relevant human systems by studying conserved behaviors and their conserved underlying neural molecular substrates. However, despite mounting evidence of deep conservation in the complex gene systems driving behavior (Saul et al, 2019a;Sinha et al, 2020;Young et al, 2019), uncertainty about the psychiatric relevance of non-human animal systems abounds in the psychiatric genetics community (National Advisory Mental Health Council Workgroup on Genomics, 2018). These doubts likely arise from longstanding and well-characterized difficulties in replicating non-human animal behavioral findings (Crabbe et al, 1999) as well as the failure to translate psychiatric genetics results from any species into the clinic (Hyman, 2012).…”