Evolution of Viral Proteins Originated De Novo by Overprinting

Sabath, Niv; Wagner, Andreas; Karlin, David

Finally, the estimated rate of evolution of most ancestral and de novo proteins ( fig. 3) is generally coherent with their function or effect on viral fitness (table 3) . For instance, the ancestral methyltransferase-guanyltransferase of tymoviruses experiences severe constraints, as expected from an enzyme, whereas the de novo protein I of betacoronaviruses, which is dispensable for replication, experiences low or no constraints. We note two exceptions: first, the orthohepadnavirus replicase gene, encoding an essential reverse transcriptase function, is not subject to very strong selective constraint (e.g., dN/dS between 0.28 and 0.78, taxon 11 in fig. 3b ). However, this discrepancy is readily explained. The overlapping region of the replicase gene in fact encodes two domains ( fig. 1 ): a disordered, hypervariable linker and the reverse transcriptase domain. The relaxed selective constraint is the result of a high dN/dS for the linker (average of 0.94) and a very low dN/dS for the reverse transcriptase domain (average of 0.15). Second, the tymovirus movement protein gene has a dN/dS of 1, suggesting an absence of selective pressure, despite encoding an important function that allows the spread of viral RNA between cells. Again, this discrepancy can be attributed to the fact that the movement protein consists of a slowly evolving region (around aa 1-400) and a fast-evolving region (C-terminal 200aa) (results not shown).