Woelk et al. [47] suggested that the reduced positive selection in vector borne RNA viruses, results from three possible trade-offs associated with the life cycle carried in both mammalian and The third addresses the differences in immune response in the two host types: Mutations facilitating immune escape or tolerance in the first host might cause the opposite effect in the second. In the present analysis the Envelope gene displays the lowest substitution rate. As it encodes the protein responsible for the induction of protective antibody response in mammals [52] , the reported rate could be explained by the third trade-off mechanism. Accordingly, the other surface-exposed structural proteins do not interact with hosts environment as strongly as the E protein (the M protein is buried under a scaffold of E dimmers and the Capsid is covered by the Envelope) and could accumulate more mutations. We conjecture that the C-gene reaches the highest substitution rates because the Capsid is not directly involved in the replication or in the mounting of an anti-viral immune response. Rate differences for nonstructural proteins could in turn be explained by the first and second trade-offs. Finally, it has been proposed that rate of replication governs the long-term substitution rate; for instance in dsDNA viruses very high replication rates may inflate the observed substitution rate [53, 54] . Within tick-borne arboviruses, the tempo of replication is the compound of phases of high replication rates following mammalian infection and phases of low to very low rates in the arthropod environment, with the phase transition commanded by a putative termo sensitive ribo-switch [55] . It is unclear how this rate shift would impact our estimate of a global rate and, as opposed to dsDNA viruses, whether the long periods of latency could deflate the observed rates.