scholarly journals Unbiased estimate of synonymous and non-synonymous substitution rates with non-stationary base composition

2017 ◽  
Author(s):  
Laurent Guéguen ◽  
Laurent Duret
Keyword(s):  
Base Composition ◽  
Evolutionary Process ◽  
Synonymous Substitution ◽  
Substitution Rates ◽  
Synonymous Mutations ◽  
Synonymous Substitution Rates ◽  
Good Proxy ◽  
Neutral Mutations ◽  
Stochastic Mapping ◽  
Codon Evolution

AbstractThe measure of synonymous and non-synonymous substitution rates (dS and dN) is useful for assessing selection operating on protein sequences or for investigating mutational processes affecting genomes. In particular, the ratio is expected to be a good proxy of ω, the probability of fixation of non-synonymous mutations relative to that of neutral mutations. Standard methods for estimating dN, dS or ω rely on the assumption that the base composition of sequences is at the equilibrium of the evolutionary process. In many clades, this assumption of stationarity is in fact incorrect, and we show here through simulations and through analyses of empirical data that non-stationarity biases the estimate of dN, dS and ω. We show that the bias in the estimate of ω can be fixed by explicitly considering non-stationarity in the modeling of codon evolution, in a maximum likelihood framework. Moreover, we propose an exact method of estimate of dN and dS on branches, based on stochastic mapping, that can take into account non-stationarity. This method can be directly applied to any kind of model of evolution of codons, as long as neutrality is clearly parameterized.

scholarly journals Synonymous Rates at the RpII215 Gene of Drosophila: Variation Among Species and Across the Coding Region

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 269-280 ◽  
Author(s):  
Ana Llopart ◽  
Montserrat Aguadé
Keyword(s):  
Rna Polymerase Ii ◽  
Molecular Clock ◽  
Constitutive Expression ◽  
Synonymous Substitution ◽  
Coding Region ◽  
Substitution Rates ◽  
Synonymous Mutations ◽  
Molecular Clock Hypothesis ◽  
Synonymous Substitution Rates ◽  
Clock Hypothesis

Abstract The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. Nonsynonymous divergence estimates (Ka) indicate that this gene has a very low rate of amino acid replacements. Given its low Ka and constitutive expression, synonymous substitution rates are, however, unexpectedly high. Sequence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a reduced effective size relative to D. subobscura. The significantly higher rate of synonymous substitutions detected in the D. guanche lineage could be explained if synonymous mutations behave as nearly neutral. Significant departure from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscura, and D. melanogaster lineages. Codon bias and synonymous divergence between D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for synonymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the rest of the protein. Synonymous substitution rates were significantly different in both regions, which strongly indicates that synonymous mutations in the CTD and in the non-CTD regions are under detectably different selection coefficients.

scholarly journals Comparing Patterns of Nucleotide Substitution Rates Among Chloroplast Loci Using the Relative Ratio Test

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 393-399 ◽  
Author(s):  
Spencer V Muse ◽  
Brandon S Gaut
Keyword(s):  
Nucleotide Substitution ◽  
Nonsynonymous Substitution ◽  
Synonymous Substitution ◽  
Joint Analysis ◽  
Ratio Test ◽  
Substitution Rates ◽  
Chloroplast Genomes ◽  
Synonymous Substitution Rates ◽  
Nucleotide Substitution Rates ◽  
Evolutionary Lineages

Even when several genetic loci are used in molecular evolutionary studies, each locus is typically analyzed independently of the others. This type of approach makes it difficult to study mechanisms and processes that affect multiple genes. In this work we develop a statistical approach for the joint analysis of two or more loci. The tests we propose examine whether or not nucleotide substitution rates across evolutionary lineages have the same relative proportions at two loci. Theses procedures are applied to 33 genes from the chloroplast genomes of rice, tobacco, pine, and liverwort. With the exception of five clearly distinct loci, we find that synonymous substitution rates tend to change proportionally across genes. We interpret these results to be consistent with a “lineage effect” acting on the entire chloroplast genome. In contrast, nonsynonymous rates do not change proportionally across genes, suggesting that locus-specific evolutionary effects dominate patterns of nonsynonymous substitution.

scholarly journals The Causes of Synonymous Rate Variation in the Rodent Genome: Can Substitution Rates Be Used to Estimate the Sex Bias in Mutation Rate?

Genetics ◽  
1999 ◽  
Vol 152 (2) ◽  
pp. 661-673 ◽  
Author(s):  
Nick G C Smith ◽  
Laurence D Hurst
Keyword(s):  
Mutation Rate ◽  
Rate Ratio ◽  
Synonymous Substitution ◽  
Sex Bias ◽  
Imprinted Genes ◽  
Rate Variation ◽  
Substitution Rates ◽  
Synonymous Substitution Rates ◽  
Male To Female ◽  
Different Parts

Abstract Miyata et al. have suggested that the male-to-female mutation rate ratio (α) can be estimated by comparing the neutral substitution rates of X-linked (X), Y-linked (Y), and autosomal (A) genes. Rodent silent site X/A comparisons provide very different estimates from X/Y comparisons. We examine three explanations for this discrepancy: (1) statistical biases and artifacts, (2) nonneutral evolution, and (3) differences in mutation rate per germline replication. By estimating errors and using a variety of methodologies, we tentatively reject explanation 1. Our analyses of patterns of codon usage, synonymous rates, and nonsynonymous rates suggest that silent sites in rodents are evolving neutrally, and we can therefore reject explanation 2. We find both base composition and methylation differences between the different sets of chromosomes, a result consistent with explanation 3, but these differences do not appear to explain the observed discrepancies in estimates of α. Our finding of significantly low synonymous substitution rates in genomically imprinted genes suggests a link between hemizygous expression and an adaptive reduction in the mutation rate, which is consistent with explanation 3. Therefore our results provide circumstantial evidence in favor of the hypothesis that the discrepancies in estimates of α are due to differences in the mutation rate per germline replication between different parts of the genome. This explanation violates a critical assumption of the method of Miyata et al., and hence we suggest that estimates of α, obtained using this method, need to be treated with caution.

scholarly journals Extensive variation in synonymous substitution rates in mitochondrial genes of seed plants

2007 ◽  
Vol 7 (1) ◽  
pp. 135 ◽  
Author(s):  
Jeffrey P Mower ◽  
Pascal Touzet ◽  
Julie S Gummow ◽  
Lynda F Delph ◽  
Jeffrey D Palmer
Keyword(s):  
Synonymous Substitution ◽  
Mitochondrial Genes ◽  
Seed Plants ◽  
Substitution Rates ◽  
Extensive Variation ◽  
Synonymous Substitution Rates

Rates of Nucleotide Substitution and Mammalian Nuclear Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to Different Conclusions

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 1299-1308 ◽  
Author(s):  
Joseph P Bielawski ◽  
Katherine A Dunn ◽  
Ziheng Yang
Keyword(s):  
Maximum Likelihood ◽  
Gc Content ◽  
Synonymous Substitution ◽  
Likelihood Methods ◽  
Approximate Methods ◽  
Substitution Rates ◽  
The Third ◽  
Maximum Likelihood Methods ◽  
Codon Positions ◽  
Synonymous Substitution Rates

Abstract Rates and patterns of synonymous and nonsynonymous substitutions have important implications for the origin and maintenance of mammalian isochores and the effectiveness of selection at synonymous sites. Previous studies of mammalian nuclear genes largely employed approximate methods to estimate rates of nonsynonymous and synonymous substitutions. Because these methods did not account for major features of DNA sequence evolution such as transition/transversion rate bias and unequal codon usage, they might not have produced reliable results. To evaluate the impact of the estimation method, we analyzed a sample of 82 nuclear genes from the mammalian orders Artiodactyla, Primates, and Rodentia using both approximate and maximum-likelihood methods. Maximum-likelihood analysis indicated that synonymous substitution rates were positively correlated with GC content at the third codon positions, but independent of nonsynonymous substitution rates. Approximate methods, however, indicated that synonymous substitution rates were independent of GC content at the third codon positions, but were positively correlated with nonsynonymous rates. Failure to properly account for transition/transversion rate bias and unequal codon usage appears to have caused substantial biases in approximate estimates of substitution rates.

Sign in / Sign up

Export Citation Format

Share Document