Molecular Biology and Evolution, Vol 16, 372-382, Copyright © 1999 by Society for Molecular Biology and Evolution
KA Crandall, CR Kelsey, H Imamichi, HC Lane and NP Salzman
Parallel or convergent evolution at the molecular level has been difficult
to demonstrate especially when rigorous statistical criteria are applied.
We present sequence data from the protease gene from eight patients
infected with the human immunodeficiency virus (HIV-1). These patients have
been on multiple drug therapies for at least 2 years. We present sequence
data from two timepoints: time zero--the initiation of drug therapy--and a
subsequent timepoint between 59 and 104 weeks after the initiation of drug
therapy. In addition to the sequence data, we present viral load data from
both initial and final timepoints. Our phylogenetic analyses indicate
significant evolution of virus from initial to final time points, even in
three of eight patients who show low viral loads. Of the five patients who
escaped drug therapy, identical amino acid replacements were seen in all
five patients at two different codon positions, an indication of parallel
evolution. We also measured genetic diversity for these patients and found
no correlation between genetic diversity and viral load. Finally, we
calculated the nonsynonymous and synonymous substitution rates and showed
that the ratio of nonsynonymous to synonymous substitution compared to the
value of one may be a poor indicator of natural selection.
ORIGINAL ARTICLE
Parallel evolution of drug resistance in HIV: failure of nonsynonymous/synonymous substitution rate ratio to detect selection
Department of Zoology, Brigham Young University, Provo, Utah 84602- 5255, USA. keith_crandall@byu.edu
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