Evolution of Viral Proteins Originated De Novo by Overprinting

Sabath, Niv; Wagner, Andreas; Karlin, David

Novel protein-coding genes can have two fundamental origins (reviewed in Long et al. 2003; Babushok et al. 2007; Bornberg-Bauer et al. 2010; Kaessmann 2010; Tautz and Domazet-Loso 2011) . In the first, a gene originates by modification of an existing gene, for example, through gene duplication, exon shuffling, gene fusion, horizontal gene transfer, or transposition. In the second, a gene originates de novo. This mechanism was thought to be highly improbable (Ohno 1970; Jacob 1977) , but recent studies have provided experimental evidence that it may be frequent. De novo origination can take place in a previously noncoding region, such as an intergenic region (Cai et al. 2008; Toll-Riera et al. 2009b; Li, Zhang, et al. 2010) , or an intron (Sorek 2007 ). However, a gene can also originate de novo from an open reading frame that already encodes a protein, by a mechanism called "overprinting", in which mutations lead to the expression of a second reading frame overlapping the first one (Ohno 1984; Keese and Gibbs 1992; Rancurel et al. 2009; Li, Dong, et al. 2010) . Genome-scale computational analyses or experimental analyses of RNA transcripts have proposed many candidate genes originated de novo through these mechanisms (Levine et al. 2006; Begun et al. 2007; Knowles and McLysaght 2009; Chen et al. 2010; Wu et al. 2011; Yang and Huang 2011) .