Fig. 2

A BS and BS-based different results. a Relative motion between gRNA strands favors topological intertwining, leading to a junction containing both donor and acceptor templates, i.e., a BS. b During reverse transcription, RT pauses as a result of an impediment from the BS. Unable to proceed, reverse transcriptase is halted. c When RT encounters a BS, it “climbs up” the acceptor template and resumes the subsequent synthesis along the acceptor template, resulting in successful strand transfer. d When RT encounters a BS, it “climbs up” the acceptor template, performs a very brief synthesis of several bases along the new template, then “climbs down” back to the donor template, and continues elongating along the initial donor template. This will lead to recombination of a very small segment. Such a segment of gene variations would be regarded as serial mutations rather than recombination because it is too short to be detected by any of the recombination analysis programs including Simplot, Recombination identification program (RIP), jumping profile hidden Markov model (jpHMM), and RDP3. As shown in the panel, the allele on the red strand is preserved in the integrated provirus, resulting in mutations (the mutations are represented by the yellow site). HIV-1 RT is represented by the gold oval, where P indicates the DNA polymerase active site and H indicates the RNase H active site. The DNA polymerase active site is engaged at the primer strand 3′ terminus, and the RNase H active site engages the template strand and performs limited template degradation as DNA synthesis proceeds. The black lines represent donor templates; the red lines represent acceptor templates. The blue line represents a nascent DNA. The level arrow indicates the direction of DNA synthesis