Dual‐Coding Regions in Alternatively Spliced Human Genes

Abstract

In eukaryotes, a coding deoxyribonucleic acid (DNA) sequence usually encodes amino acids in one reading frame only. However, by using different exon combinations, alternatively spliced genes may contain dual‐coding regions, where more than one reading frame encodes amino acid sequences. In recent years, quite a few studies have systematically identified such dual‐coding regions in the human genome. These special coding regions generate functionally related but distinct protein products, and they have evolved under unusual selective forces, with fewer synonymous sites. This article will first introduce the concept of dual‐coding regions in alternatively spliced genes through several well‐characterised examples, and then discusses the computational methods for detecting such regions and elucidating their evolutionary constraints and finally discusses the potential selective advantages. Key Concepts: The open reading frame in a DNA sequence defines the encoded amino acid sequences. Particularly low synonymous substitution rate suggests the presence of overlapping reading frames. During translation, ribosomes move along an mRNA not by one nucleotide, but by one codon at a time. The presence of in‐frame stop codons indicates that the ORF no longer encodes a functional protein product. Two reading frames of a dual‐coding region resulting from alternative splicing are in the same strand whereas those resulting from other mechanisms may be in different strands.