Overlapping gene

An overlapping gene (or OLG)^[1][2] is a gene whose expressible nucleotide sequence partially overlaps with the expressible nucleotide sequence of another gene.^[3] In this way, a nucleotide sequence may make a contribution to the function of one or more gene products. Overlapping genes are present in and a fundamental feature of both cellular and viral genomes.^[2] The current definition of an overlapping gene varies significantly between eukaryotes, prokaryotes, and viruses.^[2] In prokaryotes and viruses overlap must be between coding sequences but not mRNA transcripts, and is defined when these coding sequences share a nucleotide on either the same or opposite strands. In eukaryotes, gene overlap is almost always defined as mRNA transcript overlap. Specifically, a gene overlap in eukaryotes is defined when at least one nucleotide is shared between the boundaries of the primary mRNA transcripts of two or more genes, such that a DNA base mutation at any point of the overlapping region would affect the transcripts of all genes involved. This definition includes 5′ and 3′ untranslated regions (UTRs) along with introns.

Overprinting refers to a type of overlap in which all or part of the sequence of one gene is read in an alternate reading frame from another gene at the same locus.^[4] The alternative open reading frames (ORF) are thought to be created by critical nucleotide substitutions within an expressible pre-existing gene, which can be induced to express a novel protein while still preserving the function of the original gene.^[5] Overprinting has been hypothesized as a mechanism for de novo emergence of new genes from existing sequences, either older genes or previously non-coding regions of the genome.^[6] It is believed that most overlapping genes, or genes whose expressible nucleotide sequences partially overlap with each other, evolved in part due to this mechanism, suggesting that each overlap is composed of one ancestral gene and one novel gene.^[7] Subsequently, overprinting is also believed to be a source of novel proteins, as de novo proteins coded by these novel genes usually lack remote homologs in databases.^[8] Overprinted genes are particularly common features of the genomic organization of viruses, likely to greatly increase the number of potential expressible genes from a small set of viral genetic information.^[9] It is likely that overprinting is responsible for the generation of numerous novel proteins by viruses over the course of their evolutionary history.