Mutational Bias Affects Protein Evolution in Flowering Plants

The number of amino acids that occupy a given protein site during evolution reflects the selective constraints operating on the site. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, while the sequence entropy only depends on the equilibrium frequencies of the amino acids, the substitution rate also depends on the exchangeability matrix that describes mutations in the mathematical model of the substitution process. Here we apply two variants of a mathematical model of protein evolution with selection for protein stability, both against unfolding and against misfolding. Exploiting the approximation of independent sites, these models allow computing site-specific substitution processes that satisfy global constraints on folding stability. We find that site-specific substitution rates do not depend only on the selective constraints acting on the site, quantified through its sequence entropy. In fact, polar sites evolve faster than hydrophobic sites even for equal sequence entropy, as a consequence of the fact that polar amino acids are characterized by higher mutational exchangeability than hydrophobic ones. Accordingly, the model predicts that more polar proteins tend to evolve faster. Nevertheless, these results change if we compare proteins that evolve under different mutation biases, such as orthologous proteins in different bacterial genomes. In this case, the substitution rates are faster in genomes that evolve under mutational bias that favor hydrophobic amino acids by preferentially incorporating the nucleotide Thymine that is more frequent in hydrophobic codons. This appearingly contradictory result arises because buried sites occupied by hydrophobic amino acids are characterized by larger selective factors that largely amplify the substitution rate between hydrophobic amino acids, while the selective factors of exposed sites have a weaker effect. Thus, changes in the mutational bias produce deep effects on the biophysical properties of the protein (hydrophobicity) and on its evolutionary properties (sequence entropy and substitution rate) at the same time. The program Prot_evol that implements the two site-specific substitution processes is freely available at https://ub.cbm.uam.es/prot_fold_evol/prot_fold_evol_soft_main.php#Prot_Evol.

Download Full-text

Protein Evolution and Codon Usage Bias on the Neo-Sex Chromosomes of Drosophila miranda

Genetics ◽

10.1093/genetics/165.3.1221 ◽

2003 ◽

Vol 165 (3) ◽

pp. 1221-1232

Author(s):

Doris Bachtrog

Keyword(s):

Amino Acid ◽

Molecular Evolution ◽

Y Chromosome ◽

Protein Evolution ◽

Sex Chromosomes ◽

Codon Bias ◽

Mutational Bias ◽

Significant Heterogeneity ◽

Synonymous Mutations ◽

Ideal System

Abstract The neo-sex chromosomes of Drosophila miranda constitute an ideal system to study the effects of recombination on patterns of genome evolution. Due to a fusion of an autosome with the Y chromosome, one homolog is transmitted clonally. Here, I compare patterns of molecular evolution of 18 protein-coding genes located on the recombining neo-X and their homologs on the nonrecombining neo-Y chromosome. The rate of protein evolution has significantly increased on the neo-Y lineage since its formation. Amino acid substitutions are accumulating uniformly among neo-Y-linked genes, as expected if all loci on the neo-Y chromosome suffer from a reduced effectiveness of natural selection. In contrast, there is significant heterogeneity in the rate of protein evolution among neo-X-linked genes, with most loci being under strong purifying selection and two genes showing evidence for adaptive evolution. This observation agrees with theory predicting that linkage limits adaptive protein evolution. Both the neo-X and the neo-Y chromosome show an excess of unpreferred codon substitutions over preferred ones and no difference in this pattern was observed between the chromosomes. This suggests that there has been little or no selection maintaining codon bias in the D. miranda lineage. A change in mutational bias toward AT substitutions also contributes to the decline in codon bias. The contrast in patterns of molecular evolution between amino acid mutations and synonymous mutations on the neo-sex-linked genes can be understood in terms of chromosome-specific differences in effective population size and the distribution of selective effects of mutations.

Download Full-text

Influence of mutation bias and hydrophobicity on the substitution rates and sequence entropies of protein evolution

10.7287/peerj.preprints.26868 ◽

2018 ◽

Author(s):

María José Jiménez-Santos ◽

Miguel Arenas ◽

Ugo Bastolla

Keyword(s):

Mathematical Model ◽

Amino Acids ◽

Protein Evolution ◽

Substitution Rate ◽

Mutational Bias ◽

Mutation Bias ◽

Substitution Rates ◽

Sequence Entropy ◽

Hydrophobic Amino Acids ◽

The Mathematical Model

Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, while the sequence entropy only depends on the equilibrium frequencies of the amino acids, the substitution rate also depends on the exchangeability matrix that describes mutations in the mathematical model of the substitution process. Here we apply a mathematical model of protein evolution with selection for protein stability, both against unfolding and against misfolding, and find that sites with the same sequence entropy present different substitution rates depending on whether the site is prevalently hydrophobic or hydrophylic. For equal sequence entropy, polar sites evolve faster than hydrophobic sites. This is a consequence of the differential exchangeability associated with hydrophobic or polar amino acids. Accordingly, the model predicts that more polar proteins present, on the average, a faster substitution rate. However, these results change if we compare proteins that evolve under different mutation biases, such as orthologous proteins in different bacterial genomes. In this case, the substitution rates are faster in genomes that evolve under mutational bias that favour hydrophobic amino acids by preferentially incorporating the nucleotide Thymine that is more frequent in hydrophobic codons. In our model, the mutation bias influences both the sequence entropies and the substitution rates of protein sites. The sequence entropy is maximal for the mutational biases that reproduce the observed amino acid distributions and strongly decreases when extreme mutational biases are approached. The hydrophobicity for which the entropy is maximal is close to the mean hydrophobicity of the twenty amino acids and independent of the mutation bias. In contrast, the substitution rate and the hydrophobicity for which the substitution rate is maximal tend to increase when the mutation bias favours hydrophobic amino acids. Thus, changes of the mutational bias lead to deep effects on the biophysical properties of the protein (hydrophobicity) and on its evolutionary properties (sequence entropy and substitution rate) at the same time. The program Prot_evol is freely available for download at the url https://ub.cbm.uam.es/prot_fold_evol/prot_fold_evol_soft_main.php#Prot_Evol.[p]

Download Full-text

Influence of mutation bias and hydrophobicity on the substitution rates and sequence entropies of protein evolution

10.7287/peerj.preprints.26868v1 ◽

2018 ◽

Author(s):

María José Jiménez-Santos ◽

Miguel Arenas ◽

Ugo Bastolla

Keyword(s):

Mathematical Model ◽

Amino Acids ◽

Protein Evolution ◽

Substitution Rate ◽

Mutational Bias ◽

Mutation Bias ◽

Substitution Rates ◽

Sequence Entropy ◽

Hydrophobic Amino Acids ◽

The Mathematical Model

Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, while the sequence entropy only depends on the equilibrium frequencies of the amino acids, the substitution rate also depends on the exchangeability matrix that describes mutations in the mathematical model of the substitution process. Here we apply a mathematical model of protein evolution with selection for protein stability, both against unfolding and against misfolding, and find that sites with the same sequence entropy present different substitution rates depending on whether the site is prevalently hydrophobic or hydrophylic. For equal sequence entropy, polar sites evolve faster than hydrophobic sites. This is a consequence of the differential exchangeability associated with hydrophobic or polar amino acids. Accordingly, the model predicts that more polar proteins present, on the average, a faster substitution rate. However, these results change if we compare proteins that evolve under different mutation biases, such as orthologous proteins in different bacterial genomes. In this case, the substitution rates are faster in genomes that evolve under mutational bias that favour hydrophobic amino acids by preferentially incorporating the nucleotide Thymine that is more frequent in hydrophobic codons. In our model, the mutation bias influences both the sequence entropies and the substitution rates of protein sites. The sequence entropy is maximal for the mutational biases that reproduce the observed amino acid distributions and strongly decreases when extreme mutational biases are approached. The hydrophobicity for which the entropy is maximal is close to the mean hydrophobicity of the twenty amino acids and independent of the mutation bias. In contrast, the substitution rate and the hydrophobicity for which the substitution rate is maximal tend to increase when the mutation bias favours hydrophobic amino acids. Thus, changes of the mutational bias lead to deep effects on the biophysical properties of the protein (hydrophobicity) and on its evolutionary properties (sequence entropy and substitution rate) at the same time. The program Prot_evol is freely available for download at the url https://ub.cbm.uam.es/prot_fold_evol/prot_fold_evol_soft_main.php#Prot_Evol.[p]

Download Full-text