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

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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.

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作者简介

G. Kosovsky

Afanasyev Scientific Research Institute of Fur-Bearing Animal Breeding and Rabbit Breeding

Email: skobelolga@gmail.com
俄罗斯联邦, Rodniki, Moscow Region

O. Skobel

Afanasyev Scientific Research Institute of Fur-Bearing Animal Breeding and Rabbit Breeding

编辑信件的主要联系方式.
Email: skobelolga@gmail.com
俄罗斯联邦, Rodniki, Moscow Region

T. Glazko

Afanasyev Scientific Research Institute of Fur-Bearing Animal Breeding and Rabbit Breeding

Email: skobelolga@gmail.com
俄罗斯联邦, Rodniki, Moscow Region

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2. Fig. 1. Twelve genes protein similarities in different species compared with cattle according to STRING data.

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3. Fig. 2. Protein-protein associations of 12 structural genes, according to STRING database: (1) – in human; (2) – in mouse; (3) – in cattle; (4) – in rabbit. The colors of the edges represent associations identified from different sources (turquoise: known interactions – from curated databases; magenta: known interactions – experimentally determined; green: predicted interactions – gene neighborhood; red: predicted interactions – gene fusions; blue: predicted interactions – gene co-occurrence).

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4. Fig. 3. Fundamental biological processes of cellular life support in which proteins of 12 structural genes (kcne2, gart, tmem50b, il10rb, ifnar2, urb1, grik1, usp16, ltn1, cyyr1, app, jam2) are involved.

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