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

VL - 15

SP - 1069

EP - 1081

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 8

ER -