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Substitution model of sequence evolution for the human immunodeficiency
virus type 1 subtype B gp120 gene over the C2-V5 region.
Journal of Molecular Evolution 2001;53(1):55-62.
Anderson JP, Rodrigo AG, Learn GH, Wang Y, Weinstock H, Kalish ML,
Robbins KE, Hood L, Mullins JI.
Abstract
Phylogenetic analyses frequently rely on models of sequence evolution that
detail nucleotide substitution rates, nucleotide frequencies, and site-to-site
rate heterogeneity. These models can influence hypothesis testing and can
affect the accuracy of phylogenetic inferences. Maximum likelihood methods
of simultaneously constructing phylogenetic tree topologies and estimating
model parameters are computationally intensive, and are not feasible for
sample sizes of 25 or greater using personal computers. Techniques that initially
construct a tree topology and then use this non-maximized topology to estimate
ML substitution rates, however, can quickly arrive at a model of sequence
evolution. The accuracy of this two-step estimation technique was tested
using simulated data sets with known model parameters. The results showed
that for a star-like topology, as is often seen in human immunodeficiency
virus type 1 (HIV-1) subtype B sequences, a random starting topology could
produce nucleotide substitution rates that were not statistically different
than the true rates. Samples were isolated from 100 HIV-1 subtype B infected
individuals from the United States and a 620 nt region of the env gene was
sequenced for each sample. The sequence data were used to obtain a substitution
model of sequence evolution specific for HIV-1 subtype B env by estimating
nucleotide substitution rates and the site-to-site heterogeneity in 100 individuals
from the United States. The method of estimating the model should provide
users of large data sets with a way to quickly compute a model of sequence
evolution, while the nucleotide substitution model we identified should prove
useful in the phylogenetic analysis of HIV-1 subtype B env sequences.