Accumulation ofChanges

As discussed in the chapter by P. Deny of this volume, from characterization of the many isolates of HDV from infected patients around the world, the length of the HDV genome can change by as much as 30 nucleotides, and the nucleotide sequence can change beyond 30% (Radjef et al. 2004). In the experimental situation in which an animal is infected with a single sequence of HDV, there can quickly accumulate a small number of single nucleotide changes and even nucleotide deletions (Gudima et al. 2002; Netter et al. 1995).

Similarly, in the new model described in Sect. 3.1.2, when low amounts of functional S-HDAg are provided from a DNA master copy, the genome can continue replication for at least a year and accumulates many changes (Chang et al. 2005b). Most of the changes are single nucleotide substitutions although there are some single nucleotide deletions but no major changes in the genome size. This observed ability of HDV to continue replication in the absence of any (apparent) selective pressure and despite the accumulation of numerous sequence changes, demonstrates how successful and adaptive such a noncoding selfish RNA can be. The similarities of this to the replication of the plant viroids are striking, with the exception that because of the natural intercellular communication that exists between plant cells, the viroids-unlike HDV-do not need any helper virus to spread from cell to cell.

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