Genomics of higher nervous activity: evolutionary synteny conservatism of the genes involved in neuropathology

There is increasing evidence that the gene network with common regulatory elements that affect their expression may be involved in the manifestation of various diseases. We have previously identified 12 genes associated with neurodegenerative diseases (kcne2, gart, tmem50b, il10rb, ifnar2, urb1, grik1, usp16, ltn1, cyyr1, app, jam2), which carry in their introns the recombination product between LINE1 and BovB retrotransposons with sites of homology to different microRNAs. They also maintain high evolutionary conservatism of genetic linkage in mammals, including platypus (chromosome 17) and human (chromosome 21). In order to clarify the possible functional relationships that protect the genetic linkage, an in silico analysis of the specific expression functional features was performed. The results showed their involvement in fundamental biological processes of cell life support and the close relationship between the proteins encoded by the genes. Thus, an excess of the app gene product reduces or blocks the processes of cell excitability. A reduction in cell excitability can lead to inhibition of the expression of genes encoding proteins involved in intercellular interactions, protein synthesis, purine synthesis, activation of cell ageing, cell death, and an increase in the activity of anti-inflammatory processes. We suggest that the close linkage of the 12 genes is maintained in the evolutionary process due to this relationship and the presence of the same regulatory network elements in them, which may simultaneously correct their expression. Thus, the study of the synteny of genes closely related to neuropathologies can contribute to a deeper understanding of the genetic mechanisms regulating higher nervous activity.