Comparative analysis of the nucleotide composition biases in exons and introns of human genes

TL;DR

This study compares nucleotide composition biases in exons and introns of human genes, revealing strand asymmetries linked to transcription processes and gene expression levels, and proposes using these biases to understand evolutionary influences.

Contribution

It provides a detailed analysis of transcription-related nucleotide biases in human genes, highlighting differences between coding and noncoding regions and their relation to gene expression.

Findings

Keto-skew is highest in introns and correlates with gene expression levels.

Strand asymmetries are influenced by transcription-coupled repair and translation optimization.

Untranscribed regions show near-zero keto-skew.

Abstract

The nucleotide composition of human genes with a special emphasis on transcription-related strand asymmetries is analyzed. Such asymmetries may be associated with different mutational rates in two principal factors. The first one is transcription-coupled repair and the second one is the selective pressure related to optimization of the translation efficiency. The former factor affects both coding and noncoding regions of a gene, while the latter factor is applicable only to the coding regions. Compositional asymmetries calculated at the third position of a codon in coding (exons) and noncoding (introns, UTR, upstream and downstream) regions of human genes are compared. It is shown that the keto-skew (excess of the frequencies of G and T nucleotides over the frequencies of A and C nucleotides in the same strand) is most pronounced in intronic regions, less pronounced in coding regions, and has near zero values in untranscribed regions. The keto-skew correlates with the level of gene expression in germ-line cells in both introns and exons. We propose to use the results of our analysis to estimate the contribution of different evolutionary factors to the transcription-related compositional biases.