TY - JOUR
T1 - A codon-based model designed to describe lentiviral evolution
AU - Pedersen, Anne Mette K.
AU - Wiuf, Carsten
AU - Christiansen, Freddy B.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - A codon-based model designed to describe lentiviral evolution is developed. The model incorporates unequal base compositions in the three codon positions and selection against the CpG dinucleotide within codons to account for a deficit of this dinucleotide exhibited by lentiviral genes. The model is, to a large extent, able to account for the pattern of codon usage exhibited by the HIV1 genes gag, pol, and env, in spite of its parameter paucity. The model is extended to a similar model which operates on pentets (codons and their neighboring bases). The results obtained by the pentet model establish the importance of depression of CpGs across codon boundaries as well as within codons. The goodness of fit of the CpG depression model to the observed evolution in pairwise alignments of HIV1 sequences is assessed. The model provides a significantly better description of the observed evolution than the simpler models examined. The parameter estimates indicate that part of the unusually large biases in nucleotide frequencies observed in HIV1 genes is caused by selection against CpGs. We find that the estimates of expected numbers of substitutions, of transitions to transversions, and of synonymous to nonsynonymous substitution rates are robust to CpG depression, whereas the ratio of CpG-generating substitutions to other substitutions is strongly influenced by the choice of model.
AB - A codon-based model designed to describe lentiviral evolution is developed. The model incorporates unequal base compositions in the three codon positions and selection against the CpG dinucleotide within codons to account for a deficit of this dinucleotide exhibited by lentiviral genes. The model is, to a large extent, able to account for the pattern of codon usage exhibited by the HIV1 genes gag, pol, and env, in spite of its parameter paucity. The model is extended to a similar model which operates on pentets (codons and their neighboring bases). The results obtained by the pentet model establish the importance of depression of CpGs across codon boundaries as well as within codons. The goodness of fit of the CpG depression model to the observed evolution in pairwise alignments of HIV1 sequences is assessed. The model provides a significantly better description of the observed evolution than the simpler models examined. The parameter estimates indicate that part of the unusually large biases in nucleotide frequencies observed in HIV1 genes is caused by selection against CpGs. We find that the estimates of expected numbers of substitutions, of transitions to transversions, and of synonymous to nonsynonymous substitution rates are robust to CpG depression, whereas the ratio of CpG-generating substitutions to other substitutions is strongly influenced by the choice of model.
KW - Codon usage
KW - Codon-based model
KW - CpG depression
KW - Goodness of fit
KW - HIV1
KW - Lentivirus
UR - http://www.scopus.com/inward/record.url?scp=0031880125&partnerID=8YFLogxK
U2 - 10.1093/oxfordjournals.molbev.a026006
DO - 10.1093/oxfordjournals.molbev.a026006
M3 - Journal article
C2 - 9718734
AN - SCOPUS:0031880125
SN - 0737-4038
VL - 15
SP - 1069
EP - 1081
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
IS - 8
ER -