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. 2007 May;3(5):e91.
doi: 10.1371/journal.pcbi.0030091.

A first look at ARFome: dual-coding genes in mammalian genomes

Wen-Yu Chung  1 , Samir Wadhawan, Radek Szklarczyk, Sergei Kosakovsky Pond, Anton Nekrutenko
Affiliations

A first look at ARFome: dual-coding genes in mammalian genomes

Wen-Yu Chung et al. PLoS Comput Biol. 2007 May.

Abstract

Coding of multiple proteins by overlapping reading frames is not a feature one would associate with eukaryotic genes. Indeed, codependency between codons of overlapping protein-coding regions imposes a unique set of evolutionary constraints, making it a costly arrangement. Yet in cases of tightly coexpressed interacting proteins, dual coding may be advantageous. Here we show that although dual coding is nearly impossible by chance, a number of human transcripts contain overlapping coding regions. Using newly developed statistical techniques, we identified 40 candidate genes with evolutionarily conserved overlapping coding regions. Because our approach is conservative, we expect mammals to possess more dual-coding genes. Our results emphasize that the skepticism surrounding eukaryotic dual coding is unwarranted: rather than being artifacts, overlapping reading frames are often hallmarks of fascinating biology.

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Conflict of interest statement

Competing interests. The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Three Known Examples of Mammalian Dual-Coding Genes
(A) A transcript of the Gnas1 gene contains two reading frames and produces two structurally unrelated proteins, XLαs and ALEX, by differential utilization of translation start sites. (B) A newly transcribed XBP1 mRNA can only produce protein XBP1U from ORF A. Removal of a 26-bp spacer (yellow rectangle) joins the beginning of ORF A with ORF B and translates into a different product called XBP1S. (C) Ink4a generates two splice variants that use different reading frames within exon E2 to produce the proteins p16Ink4a and p19ARF (exon names as in [8]).
Figure 2
Figure 2. mRNAs from Human and Mouse Are Aligned
Mouse mRNAs are indicated by lowercase letters. Each of the two mRNAs contains an annotated coding region (white boxes). Our algorithm looks for ARFs (black boxes) that are shifted one (shown) or two nucleotides relative to the annotated frame. The locations of the ARFs must be conserved between the species. Specifically, the ARFs in the two species must overlap for at least 500 bp.
See this image and copyright information in PMC

References

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