Nucleic Acids Research Advance Access first published online on September 26, 2006
This version published online on October 5, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl669
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Sequence determinants of breakpoint location during HIV-1 intersubtype recombination
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University Cleveland, OH 44106, USA 1 Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, Institut Pasteur 25 Rue du Dr Roux, Paris, Cedex 15, 75724 France 2 Faculty of Life Sciences, University of Manchester Manchester M13 9PT, UK
*To whom correspondence should be addressed. Tel: +33 01 45 68 85 05; Fax:+33 01 45 68 83 99; Email: matteo{at}pasteur.fr
Received July 20, 2006. Revised August 30, 2006. Accepted August 30, 2006.
Retroviral recombination results from strand switching, during reverse transcription, between the two copies of genomic RNA present in the virus. We analysed recombination in part of the envelope gene, between HIV-1 subtype A and D strains. After a single infection cycle, breakpoints clustered in regions corresponding to the constant portions of Env. With some exceptions, a similar distribution was observed after multiple infection cycles, and among recombinant sequences in the HIV Sequence Database. We compared the experimental data with computer simulations made using a program that only allows recombination to occur whenever an identical base is present in the aligned parental RNAs. Experimental recombination was more frequent than expected on the basis of simulated recombination when, in a region spanning 40 nt from the 5' border of a breakpoint, no more than two discordant bases between the parental RNAs were present. When these requirements were not fulfilled, breakpoints were distributed randomly along the RNA, closer to the distribution predicted by computer simulation. A significant preference for recombination was also observed for regions containing homopolymeric stretches. These results define, for the first time, local sequence determinants for recombination between divergent HIV-1 isolates.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.