Retrovirus recombination depends on the length of sequence identity and is not error prone

Abstract

Retroviruses, as a result of the presence of two identical genomic RNA molecules in their virions, recombine at a high rate. When nonhomologous RNA is present in the dimer RNA molecules, nonhomologous recombination can occur, although the rate is very low, only 0.1% of the rate of essentially homologous recombination (J. Zhang and H. M. Temin, Science 259:234-238, 1993). We found, as is found in naturally occurring highly oncogenic retroviruses (J. Zhang and H. M. Temin, J. Virol. 67:1747-1751, 1993), that the crossovers usually occur at a short region of sequence identity. We modified the previously studied vectors to study the effect of different lengths of short regions of sequence identity in the midst of otherwise nonidentical sequences. We found that the efficiency of recombination depends on the length of this sequence identity. However, the highest rate in such molecules remained lower than for recombination between essentially homologous molecules, even when there was extensive sequence identity. Junction sequences of the recombinants indicated that retrovirus recombination is not an error-prone process as was reported for human immunodeficiency virus reverse transcriptase by using a cell-free system (J. A. Peliska and S. J. Benkovic, Science 258:1112-1118, 1992).