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Remarkably, de novo mutations were nearly absent from the most conserved, replication-critical regions of the PSTVd genome, suggesting that sequence conservation is a consequence of both essential function and template optimization for greater Pol II fidelity. Such biased fidelity may constitute a novel strategy to ensure population success while allowing abundant sampling of sequence space in other genome regions. Comparison with variants in progeny populations derived from a cloned, wild type PSTVd master sequence revealed that most d