Vladimir Babenko1* and Timophey Boltunov1
1Institute of Cytology and Genetics, Novosibirisk, 640090, Russia
bob [at] bionet.nsc.ru
Abstract
Based on the animal model of agonistic interactions, we observed co-varied (linked) alternative exons (LEs) in the genes with alternative splicing phenotype in brain. As a result, we have found 263 positively co-varied pairs, and 26 pairs with negative co-variation. To ascertain the data consistency, we employed three organisms cross-validation: human, mouse and rat with available hippocampus brain region SRA repositories, which supported the co-varied effect of the corresponding exons.
From 142 genes with LE events the maximum LE pairs were observed in insulin – related Sorbs1 (Sorbin And SH3 Domain Containing 1; 18 LE AS events), and synaptic Nrcam (12 LE events). 104 genes maintain only 1 LE pair and 36 genes maintain 2-7 LE pairs. Notably there is a mode at 3 LE pairs per gene (14 genes) in genes vs LE events distribution. GO analysis reveals that the majority of genes maintaining LE events have belong to the synaptic genes, RNA-splicing machinery, and chromatin remodeling.
The ‘complexity’ (entropic) measure of gene is calculated as , where (Ψ) psi is a percent inclusion rate of a particular AS exon, n – number of AS exons in the gene. It is evident that linked AS exons decrease gene complexity rate, allowing coordinated splicing in high splicing dynamics rate genes, such as synaptic, RNA processing, chromatin remodeling genes. Herein we speculate if LE AS events are of evolutionary advantage for the high splicing turnover genes working in homeostasis equilibrium.
Next step of the work is to elucidate features providing the linking phenomenon, including mRNA secondary structure, the splicing factor binding sites within and around the corresponding exons.
We will present the results on the issue featuring some complex interactions between exons.
Keywords: alternative splicing, entropy, evolution
Acknowledgement: The study was supported by the Russian Science Foundation (grant no. 19-15-00026).
