The greater than twofold cost of integration for retroviruses

Abstract

Sexual reproduction, typically conceived of as a puzzling feature of eukaryotes, has posed an extraordinary evolutionary challenge in terms of the twofold replicative advantage of asexual over sexual organisms. Here we show mathematically that a greater than twofold 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 transcription into the haploid DNA phase serves to generate diversity followed by a phase of transcriptional clonal expansion during the restoration of diploidy from a stable, long lived, DNA encoded provirus.