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Mutation pressure mediates a pattern of substitution rates with latitude and climate in carnivores.

ABSTRACT: The evolutionary patterns of the mitochondrial genome are influenced by both adaptive and nonadaptive forces, with their contributions varying among taxa. There appears to be a correlation linking mutagenesis and latitude, which could be due to differences in metabolic rates. These discrepancies in metabolic rates exhibit a positive connection with mutation pressure. On this basis, we hypothesise that nonadaptive forces play a role in the differences in mutation rates observed along latitudinal gradients. In this study, we selected widely distributed carnivores as representatives of mammals to test our hypothesis. We examined the correlations between the dN/dS ratio (ω), as well as the substitution rates (dS and dN), of 13 PCGs in the mtDNA of 122 carnivores, and the latitude and climatic factors. We found that taxa distributed in higher latitudes tend to have higher substitution rates, but not ω values indicating selective pressure. Notably, dN shows a strong positive correlation with dS, although dS is primarily influenced by mutation pressure, while dN is also influenced by effective population size (N _e ). Phylogenetic generalised least squares (PGLS) regression analyses showed that both substitution rates were correlated with climatic factors representing the temperature, precipitation and variability of climate. Based on our findings, we propose that the mutations are primarily influenced by nonadaptive forces (mutation pressure). This forms the fundamental premise for natural selection and speciation. Moreover, the correlation between substitution rates and latitudinal distribution and climate, which are outcomes of nonadaptive factors, can aid in comprehending the global distribution of species diversity.

SUBMITTER: Zhao C

PROVIDER: S-EPMC11347990 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Mutation pressure mediates a pattern of substitution rates with latitude and climate in carnivores.

Zhao Chao C Liu Guangshuai G Yang Xiufeng X Wang Xibao X Zhou Shengyang S Liu Zhao Z Liu Kangning K Zhang Honghai H

Ecology and evolution 20240827 8

The evolutionary patterns of the mitochondrial genome are influenced by both adaptive and nonadaptive forces, with their contributions varying among taxa. There appears to be a correlation linking mutagenesis and latitude, which could be due to differences in metabolic rates. These discrepancies in metabolic rates exhibit a positive connection with mutation pressure. On this basis, we hypothesise that nonadaptive forces play a role in the differences in mutation rates observed along latitudinal ...[more]

PMID: 39193169

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Project description:BackgroundMutation rates are consistently varied in cancer genome and play an important role in tumorigenesis, however, little has been known about their function potential and impact on the distribution of functional mutations. In this study, we investigated genomic features which affect mutation pattern and the function importance of mutation pattern in cancer.MethodsSomatic mutations of clear-cell renal cell carcinoma, liver cancer, lung cancer and melanoma and single nucleotide polymorphisms (SNPs) were intersected with 54 distinct genomic features. Somatic mutation and SNP densities were then computed for each feature type. We constructed 2856 1-Mb windows, in which each row (1-Mb window) contains somatic mutation, SNP densities and 54 feature vectors. Correlation analyses were conducted between somatic mutation, SNP densities and each feature vector. We also built two random forest models, namely somatic mutation model (CSM) and SNP model to predict somatic mutation and SNP densities on a 1-Kb scale. The relation of CSM and SNP scores was further analyzed with the distributions of deleterious coding variants predicted by SIFT and Mutation Assessor, non-coding functional variants evaluated with FunSeq 2 and GWAVA and disease-causing variants from HGMD and ClinVar databases.ResultsWe observed a wide range of genomic features which affect local mutation rates, such as replication time, transcription levels, histone marks and regulatory elements. Repressive histone marks, replication time and promoter contributed most to the CSM models, while, recombination rate and chromatin organizations were most important for the SNP model. We showed low mutated regions preferentially have higher densities of deleterious coding mutations, higher average scores of non-coding variants, higher fraction of functional regions and higher enrichment of disease-causing variants as compared to high mutated regions.ConclusionsSomatic mutation densities vary largely across cancer genome, mutation frequency is a major indication of function and influence on the distribution of functional mutations in cancer.

Project description:Mutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, in Escherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.IMPORTANCE It has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. Using Escherichia coli as our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.

Project description: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.

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Mutation pressure mediates a pattern of substitution rates with latitude and climate in carnivores.

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Mutation pressure mediates a pattern of substitution rates with latitude and climate in carnivores.

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