An exploratory algorithm to identify intra-host recombinant viral sequences.
Since recombination leads to the generation of mosaic genomes that violate the assumption of traditional phylogenetic methods that sequence evolution can be accurately described by a single tree, results and conclusions based on phylogenetic analysis of data sets including recombinant sequences can be severely misleading. Many methods are able to adequately detect recombination between diverse sequences, for example between different HIV-1 subtypes. More problematic is the identification of recombinants among closely related sequences such as a viral population within a host. We describe a simple algorithmic procedure that enables detection of intra-host recombinants based on split-decomposition networks and a robust statistical test for recombination. By applying this algorithm to several published HIV-1 data sets we conclude that intra-host recombination was significantly underestimated in previous studies and that up to one-third of the env sequences longitudinally sampled from a given subject can be of recombinant origin. The results show that our procedure can be a valuable exploratory tool for detection of recombinant sequences before phylogenetic analysis, and also suggest that HIV-1 recombination in vivo is far more frequent and significant than previously thought.
Salemi
Marco
M
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, College of Medicine, 1376 Mowry Road, P.O. Box 106633, Gainesville, FL 32610, USA. salemi@pathology.ufl.edu
Gray
Rebecca R
RR
Goodenow
Maureen M
MM
D000465:Algorithms; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005828:Genetics, Population; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D010802:Phylogeny; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D004279:DNA, Viral
J Virol. 2007 Apr;81(7):3369-76
17251288
J Virol. 1995 Aug;69(8):5087-94
7541846
J Mol Evol. 1992 Feb;34(2):126-9
1556748
Trends Ecol Evol. 2001 Jan 1;16(1):37-45
11146143
J Gen Virol. 1979 Jan;42(1):1-26
215703
Mol Biol Evol. 1998 Mar;15(3):326-35
9501499
Bioinformatics. 2006 Dec 15;22(24):3096-8
17110367
Math Biosci. 1990 Mar;98(2):185-200
2134501
AIDS. 2000;14 Suppl 3:S31-44
11086847
PLoS Pathog. 2007 Nov;3(11):e177
18020705
Mol Biol Evol. 2004 Oct;21(10):1902-12
15215321
Nature. 1995 Jan 12;373(6510):123-6
7816094
Bioinformatics. 2007 Nov 15;23(22):2993-3000
17717035
Nature. 1997 May 8;387(6629):183-8
9144289
J Virol. 2002 Nov;76(21):10674-84
12368309
J Virol. 2007 May;81(9):4492-500
17314156
Genetics. 2006 Apr;172(4):2665-81
16489234
J Virol. 2005 Jan;79(1):353-63
15596829
J Virol. 1999 Jan;73(1):152-60
9847317
Mol Biol Evol. 2006 Oct;23(10):1891-901
16818476
J Virol. 1995 Feb;69(2):669-74
7529334
J Virol. 2002 Nov;76(22):11273-82
12388687
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4204-9
15010526
Mol Biol Evol. 2004 Feb;21(2):255-65
14660700
AIDS Res Hum Retroviruses. 2005 Oct;21(10):897-900
16225419
Nature. 2002 Jul 11;418(6894):144
12110879
Mol Biol Evol. 1989 Sep;6(5):526-38
2677599
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2187-91
10051616
Comput Appl Biosci. 1996 Aug;12(4):291-5
8902355
Mol Biol Evol. 2001 Oct;18(10):1929-39
11557798
Infect Genet Evol. 2005 Jan;5(1):85-95
15567142
J Gen Virol. 2003 Apr;84(Pt 4):885-95
12655089
Genetics. 2004 Aug;167(4):1573-83
15342499
Mol Biol Evol. 2002 May;19(5):708-17
11961104
J Virol. 1999 Oct;73(10):8720-31
10482626
Bioinformatics. 2000 Jun;16(6):562-3
10980155
Mol Biol Evol. 2006 Feb;23(2):254-67
16221896
AIDS. 2004 Jan 23;18(2):153-9
15075531
AIDS Res Hum Retroviruses. 2001 Mar 20;17(5):423-31
11282011
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13757-62
11717435
Genetics. 2000 Oct;156(2):879-91
11014833