MOLECULAR DIVERGENCE OF THE DENDRITIC TRANSCRIPTOME IN RODENT NEURONS

Neurons have highly polarized architectures which require complex molecular organization, partly mediated by RNA localization. Neurons leverage the localization of mRNA to modify synaptic features by locally translating and altering protein concentrations in response to stimuli. The resulting activity-dependent modifications are essential for synaptic plasticity, and consequently, fundamental for learning and memory. While a tremendous amount of work has been dedicated to identifying spatially controlled genes, only a few studies have examined the evolution of dendritic mRNA localization. Surprisingly, work by Francis et al (2014) found that the dendritic transcriptome, the cohort of mRNA recruited into the dendrites, diverges greatly between mouse and rat, suggesting rapid evolution of a molecular phenotype often considered to be highly conserved [1]. Here, I used subcellular RNA-sequencing of dendrites and soma from the same Sprague–Dawley rat neurons to compare to a similarly detailed existing dataset for C57BL/6 mouse [2]. Analysis of the subcellular RNA-sequencing data identified 3,318 orthologous genes (2,471 and 2,358 in mouse and rat dendrites respectively) that are dendritically expressed in at least one of the two species. Interspecies comparisons of the dendritic transcriptomes revealed 960 orthologs with conserved localization, 847 orthologs being present in mouse dendrites only and 1,511 orthologs in rat dendrites only, further characterizing the divergence in the subcellular localization of many genes. Functional characterization of the divergently localized genes and paralog analysis suggests conservation of molecular functions by compensatory expression of related paralogs of divergently localized genes. Subsequent analysis of the molecular evolution of genes in each localization category, along with 964 somatic genes for comparison, suggests higher rates of base pair substitution in genes with divergent localization compared to those dendritically expressed in both species. In short, we not only confirmed Francis et al’s observation that dendritic localization occurs in a species-specific manner but also uncovered evidence of compensatory subcellular expression and identified sequence differences might underlie the changes in subcellular expression of specific genes. [1] S. A. Middleton, J. Eberwine, and J. Kim, “Comprehensive catalog of dendritically localized mRNA isoforms from sub-cellular sequencing of single mouse neurons,” BMC Biol, vol. 17, no. 1, p. 5, Dec. 2019, doi: 10.1186/s12915-019-0630-z.[2] C. Francis et al., “Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution,” BMC Genomics, vol. 15, no. 1, p. 883, Dec. 2014, doi: 10.1186/1471-2164-15-883.