Point Mutant Frequencies in the pol Gene of Human Immunodeficiency Virus Type 1 Are Two- to Threefold Lower Than Those of env

Abstract

Nucleotide sequences have been determined for the HIV-1 genomic regions encoding codons 41–108 and 181–219 of reverse transcriptase (RT) (pol gene), and codons 198–331 of gp120 (the C2V3 domains; env gene). Eighty-one HIV-1 samples from patients treated or untreated with RT inhibitors were used to sequence pol and 28 HIV-1 samples were used to sequence env. Several individual quasispecies have also been analyzed. All HIV-1 isolates belonged to subtype B. Point mutant frequencies and nucleotide diversities for pol were at most two- to threefold lower than env, with the proportion of nonsynonymous mutations ranging from 33 to 67%. A new variability index that takes into account the type of amino acid substitution as well as genetic distances between the compared sequences is introduced, and its main features for sequence comparisons emphasized. Extension of the calculations to gag, pol, and env sequences contained in the current HIV-1 database confirmed the high mutant frequencies for all HIV-1 genomic regions. The results indicate that although env is more tolerant to insertions and deletions than pol, point mutant frequencies for HIV-1 regions encoding nonstructural proteins are only two- to threefold lower than for regions encoding structural proteins. This implies the occurrence of frequent changes in HIV-1 phenotypes that are dependent on amino acid substitutions in viral enzymes.