A scale-free analysis of the HIV-1 genome demonstrates multiple conserved regions of structural and functional importance

by Jordan P. Skittrall, Carin K. Ingemarsdotter, Julia R. Gog, Andrew M. L. Lever HIV-1 replicates via a low-fidelity polymerase with a high mutation rate; strong conservation of individual nucleotides is highly indicative of the presence of critical structural or functional properties. Identifying such conservation can reveal novel insights into viral behaviour. We analysed 36 51 publicly available sequences for the presence of nucleic acid conservation beyond that required by amino acid constraints, using a novel scale-free method that identifies regions of outlying score together with a codon scoring algorithm. Sequences with outlying score were further analysed using a n algorithm for producing local RNA folds whilst accounting for alignment properties. 11 different conserved regions were identified, some corresponding to well-knowncis-acting functions of the HIV-1 genome but also others whose conservation has not previously been noted. We identify rational causes for many of these, includingcis functions, possible additional reading frame usage, a plausible mechanism by which the central polypurine tract primes second-strand DNA synthesis and a conformational stabilising function of a region at the 5 ′ end ofenv.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research