Molecular Biology and Evolution 18:1231-1245 (2001)
© 2001 Society for Molecular Biology and Evolution
HIV-1 and HIV-2 LTR Nucleotide Sequences: Assessment of the Alignment by N-block Presentation, "Retroviral Signatures" of Overrepeated Oligonucleotides, and a Probable Important Role of Scrambled Stepwise Duplications/Deletions in Molecular Evolution
*Laboratoire Génome et Informatique, Université de Versailles Saint Quentin-en-Yvelines, Versailles, France
Laboratoire d'Informatique Fondamentale de Lille, Equipe Bioinformatique, Université des Sciences et Technologie de Lille, Villeneuve d'Ascq, France
Deutsches Krebsforschungszentrum Theoretische Bioinformatik (H0300) Im Neuenheimer Feld 280, Heidelberg, Germany
Institut de Génétique Humaine, Montpellier, France
Previous analyses of retroviral nucleotide sequences, suggest a so-called "scrambled duplicative stepwise molecular evolution" (many sectors with successive duplications/deletions of short and longer motifs) that could have stemmed from one or several starter tandemly repeated short sequence(s). In the present report, we tested this hypothesis by focusing on the long terminal repeats (LTRs) (and flanking sequences) of 24 human and 3 simian immunodeficiency viruses. By using a calculation strategy applicable to short sequences, we found consensus overrepresented motifs (often containing CTG or CAG) that were congruent with the previously defined "retroviral signature." We also show many local repetition patterns that are significant when compared with simply shuffled sequences. First- and second-order Markov chain analyses demonstrate that a major portion of the overrepresented oligonucleotides can be predicted from the dinucleotide compositions of the sequences, but by no means can biological mechanisms be deduced from these results: some of the listed local repetitions remain significant against dinucleotide-conserving shuffled sequences; together with previous results, this suggests that interspersed and/or local mononucleotide and oligonucleotide repetitions could have biased the dinucleotide compositions of the sequences. We searched for suggestive evolutionary patterns by scrutinizing a reliable multiple alignment of the 27 sequences. A manually constructed alignment based on homology blocks was in good agreement with the polypeptide alignment in the coding sectors and has been exhaustively assessed by using a multiplied alphabet obtained by the promising mathematical strategy called the N-block presentation (taking into account the environment of each nucleotide in a sequence). Sector by sector, we hypothesize many successive duplication/deletion scenarios that fit our previous evolutionary hypotheses. This suggests an important duplication/deletion role for the reverse transcriptase, particularly in inducing stuttering cryptic simplicity patterns.