Relationships among the nucleotide content of human genome sequence, gene structure, and gene expression features (PhD synopsis)

TL;DR

This study investigates the relationship between nucleotide content asymmetry in human genome sequences, gene structure, and expression, revealing distinct biases in exons and introns linked to gene activity.

Contribution

It introduces new insights into nucleotide asymmetry patterns in human genes and develops novel bioinformatics tools and a database for genome sequence analysis.

Findings

Exons show purine bias; introns exhibit keto-amino skew.

Skew patterns correlate with gene expression levels.

Developed new tools for genome sequence mining and analysis.

Abstract

The Dissertation is focused on the studies of associations between functional elements in human genome and their nucleotide structure. The asymmetry in nucleotide content (skew, bias) was chosen as the main feature for nucleotide structure. A significant difference in nucleotide content asymmetry was found for human exons vs. introns. Specifically, exon sequences display bias for purines (i.e., excess of A and G over C and T), while introns exhibit keto-amino skew (i.e. excess of G and T over A and C). The extents of these biases depend upon gene expression patterns. The highest intronic keto-amino skew is found in the introns of housekeeping genes. In the case of introns, whose sequences are under weak repair system, the AT->GC and CG->TA substitutions are preferentially accumulated. A comparative analysis of gene sequences encoding cytochrome P450 2E1 of Homo sapiens and representative mammals was done. The cladistic tree on the basis of coding sequences similarity of the gene Cyp2e1 was constructed. A new programming tools of NCBI database sequence mining and analysis was developed, resulting in construction of a own database.