The Greater than Two-fold Cost of Intergration for Retroviruses

Sexual reproduction, typically conceived of as a puzzling feature of eukaryotes, has posed an extraordinary evolutionary challenge in terms of the two-fold replicative advantage of asexuals over sexuals. Here we show mathematically that a greater than two fold cost is paid by retroviruses such as HIV during reverse transcription. For a retrovirus replication is achieved through RNA reverse transcription and the effectively linear growth processes of DNA transcription during gene expression. Retroviruses are unique among viruses in that they show an alternation of generations between a diploid free living phase and a haploid integrated phase. Retroviruses engage in extensive recombination during the synthesis of the haploid DNA provirus. Whereas reverse transcription generates large amounts of sequence variation, DNA transcription is a high fidelity process. Retroviruses come under strong selection pressures from immune systems to generate escape mutants, and reverse transciption into the haploid DNA phase serves to generate diversity followed by a phase of transcriptional clonal expansion during the restoration of diploidity.

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