AEGiS-12IAC: Possible restrictions of G-->A hypermutation on HIV-1 genome.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Possible restrictions of G-->A hypermutation on HIV-1 genome.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:22 (abstract no. 11200)

Rabinovich R, Marquina S, Gutson D, Libonatti O
University of Buenos Aires, Argentina.

OBJECTIVE: To study possible restrictions of preferential mutations imposed by overlapping open reading frames and the conservation of HIV-1 RNA secondary structure stability.

MATERIALS AND METHODS: All possible G-->A and A-->G substitutions were simulated one at each time on nucleotide sequence of the env gen of HIVMN. For each simulated sequence, the free energy folding of RNA molecule was calculated. This energy was compared to the one of the wild type RNA molecule. Mfold program designed by Zucker was used.

RESULTS: Through the whole env gene, G-->A mutations resulted in a loss of RNA stability in average per mutation of 1.20 Kcal/mol. Instead, A-->G changes lead to a gain of RNA stability of 0.96 Kcal/mol. When taking into account whether the mutated nucleotide was paired or not, it happened that the loss of stability was greater when the residue was paired in the case of G-->A mutations, but in the case of paired A mutated to G there was not any loss of energy, instead, the gain of stability was lower than in the case of unpaired A. The preferential usage of codons with A in the third position (NNA) was restrained in regions of overlapping open reading frames. Hence, in the region where gag and pol overlap, the NNA/NNG ratio was 1 for the gag ORF and 2 for pol gene. These ratios were lower than those calculated for each whole gene (gag: 2.5 and pol: 3.17).

CONCLUSION: In lentiviruses, the A richness has been associated with a preferred G-->A substitution. Although amino acid sequence conservation can restrain the accumulation of A, as it was demonstrated in overlapping genes, conservation of RNA secondary structure stability would be an additional restriction of G(rho)A hypermutation.

Keywords: AEGIS, HIV-1, Genes, env, Genes, pol, Base Sequence, Genome, Amino Acid Sequence, Genome, Viral, Lentivirus, Open Reading Frames, Codon, Mutation, genetics, ICA12
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