Papillomaviruses have been evolving alongside their hosts for at least 450 million years. This review will discuss some of the insights gained into the evolution of this diverse family of viruses. Papillomavirus evolution is constrained by pervasive purifying selection to maximize viral fitness. Yet these viruses need to adapt to changes in their environment, e.g., the host immune system. It has long been known that these viruses evolved a codon usage that doesn't match the infected host. Here we discuss how papillomavirus genomes evolve by acquiring synonymous changes that allow the virus to avoid detection by the host innate immune system without changing the encoded proteins and associated fitness loss. We discuss the implications of studying viral evolution, lifecycle, and cancer progression.
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