Evolution of Viral Proteins Originated De Novo by Overprinting

Sabath, Niv; Wagner, Andreas; Karlin, David

The identification of de novo genes in viruses does not suffer from these problems or to a much lesser extent. This holds especially for genes generated by overprinting. Overlapping genes are very common in viral genomes (Belshaw et al. 2007; Chirico et al. 2010) , providing an abundant source of such de novo genes. In addition, in most cases, the expression of their protein product has been proven, and their function is at least partly known (Rancurel et al. 2009 ). Finally, using overlapping genes allows the identification of proteins originated de novo with high reliability (see later), by avoiding the confounding factors that limit current approaches to identify proteins generated de novo from noncoding sequences (Guerzoni and McLysaght 2011) . For brevity, we will refer here to de novo genes as genes that originated through overprinting. Viral de novo genes often encode proteins that play a role in viral pathogenicity or spreading, rather than proteins central to viral replication or structure (Li and Ding 2006; Rancurel et al. 2009 ). The majority of these proteins are predicted to be structurally disordered, i.e., they lack a stable three-dimensional structure (Dyson and Wright 2005; Tompa 2005; Sickmeier et al. 2007 ), but those that are ordered have intriguing structural features (Rancurel et al. 2009 ). For instance, the protein p19, originated de novo in the plant virus family Tombusviridae (Rancurel et al. 2009 ), has a previously unknown tertiary structure and a previously unknown mode of binding to small interfering RNAs (Vargason et al. 2003) . This suggests that de novo gene origination can lead to evolutionary innovations in protein structure and function (Rancurel et al. 2009; Bornberg-Bauer et al. 2010; Kaessmann 2010; Abroi and Gough 2011) .