Yang, Wa; (2004) The evolution of human AIDS viruses. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

I investigated variable selective pressures among amino acid sites in HIV-1 genes. Selective pressure at the amino acid level was measured using the nonsynonymous/synonymous substitution rate ratio. Likelihood ratio tests detected positive selection in every gene in the genome, with the majority located in gp160. Most HIV-1 genes were evolving at a subtype specific manner. As adaptive evolution is driven chiefly by immune detection, this change of selective constraint was indicative of variations in immune targeting. Differences in selective pressure contributed to the extensive genetic diversity observed across the genome and could be viewed as co-evolution of the subtypes. I measured the physiochemical properties of amino acids and found that those at positive selection sites were more diverse than those at variable sites. Furthermore, amino acid residues at exposed positive selection sites were more physiochemically diverse than at buried positive selection sites. I also examined the evolution of HIV-2 and SIVmac after the cross-species transmissions. My results indicated that HIV-2 did not appear to be evolving at a faster rate than the progenitor lineages. It is possible that fewer adaptive changes in the progenitor virus were required for successful infection. A notably different pattern was observed for SIVmac lineages. My findings showed that SIVmac lineages appeared to be evolving much faster than HIV-2. Also a fraction of sites in SIVmac lineages that were evolving by relaxed functional constraint became positively selected post zoonosis.

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