New methods for estimating the numbers of synonymous and nonsynonymous substitutions

1995 ◽  
Vol 40 (2) ◽  
pp. 190-226 ◽  
Author(s):  
Yasuo Ina
2001 ◽  
Vol 75 (6) ◽  
pp. 3004-3009 ◽  
Author(s):  
Ling Lu ◽  
Tatsunori Nakano ◽  
Etsuro Orito ◽  
Masashi Mizokami ◽  
Betty H. Robertson

ABSTRACT Four hepatitis C virus genome regions (the core, E1, HVR1, and NS5b) were amplified and sequenced from yearly samples obtained from a chronically infected chimpanzee over a 12-year span. Nucleotide substitutions were found to accumulate in the core, E1, and HVR1 regions during the course of chronic infection; substitutions within the NS5b region were not detected for the first 8 years and were found to be minimal during the last 4 years. The rate of accumulation of mutations in the core and E1 regions, based on a direct comparison between the first 1979 sequence and the last 1990 sequence, was 1.120 × 10−3, while phylogenetic ancestral comparison using the 12 yearly sequences showed a rate of 0.816 × 10−3bases per site per year. Temporal evaluation of the sequences revealed that there appeared to be periods in which substitutions accumulated and became fixed, followed by periods with relative stasis or random substitutions that did not persist. Synonymous and nonsynonymous substitutions within the core, E1, and HVR1 regions were also analyzed. In the core and E1 regions, synonymous substitutions predominated and gradually increased over time. However, within the HVR1 region, nonsynonymous substitutions predominated but gradually decreased over time.


2000 ◽  
Vol 74 (9) ◽  
pp. 4335-4350 ◽  
Author(s):  
Yumi Yamaguchi-Kabata ◽  
Takashi Gojobori

ABSTRACT To elucidate the evolutionary mechanisms of the human immunodeficiency virus type 1 gp120 envelope glycoprotein at the single-site level, the degree of amino acid variation and the numbers of synonymous and nonsynonymous substitutions were examined in 186 nucleotide sequences for gp120 (subtype B). Analyses of amino acid variabilities showed that the level of variability was very different from site to site in both conserved (C1 to C5) and variable (V1 to V5) regions previously assigned. To examine the relative importance of positive and negative selection for each amino acid position, the numbers of synonymous and nonsynonymous substitutions that occurred at each codon position were estimated by taking phylogenetic relationships into account. Among the 414 codon positions examined, we identified 33 positions where nonsynonymous substitutions were significantly predominant. These positions where positive selection may be operating, which we call putative positive selection (PS) sites, were found not only in the variable loops but also in the conserved regions (C1 to C4). In particular, we found seven PS sites at the surface positions of the α-helix (positions 335 to 347 in the C3 region) in the opposite face for CD4 binding. Furthermore, two PS sites in the C2 region and four PS sites in the C4 region were detected in the same face of the protein. The PS sites found in the C2, C3, and C4 regions were separated in the amino acid sequence but close together in the three-dimensional structure. This observation suggests the existence of discontinuous epitopes in the protein's surface including this α-helix, although the antigenicity of this area has not been reported yet.


1999 ◽  
Vol 49 (3) ◽  
pp. 330-342 ◽  
Author(s):  
Fernando Alvarez-Valin ◽  
Kamel Jabbari ◽  
Nicolas Carels ◽  
Giorgio Bernardi

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