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1.
The occurrence frequencies of nucleotide bases are biased to those of T and A bases even at third codon positions for conserved amino acid residues with fourfold degeneracy in the chloroplasts of land plants. Regarding this bias as the result of selection, the base changes at these positions are fully analyzed theoretically in terms of mutation and selection. Although the degree of bias is considerably different depending on the lineages of land plants, the theoretical curves considering the influence of selection in the respective lineages provide a reasonable set of evolutionary distances for the relative base change probabilities estimated empirically from base changes enumerated in the comparison of rbcL genes. By using the fossil records of earliest seed plants in the Late Devonian and of uniaperturate and triaperturate pollen types in the early stage of the Cretaceous as calibration points, the divergence of Marchantiidae and a common ancestor of other land plants is estimated to have occurred 509 Mya, together with the estimation of a mutation rate of 1.45 × 10–9 year–1 per site. The other bryophytes such as Bryopsida, Anthocerotopsida, and Jungermanniidae are sister groups to tracheophytes, the divergence of bryophytes and tracheophytes being estimated to have occurred 483 Mya. The evolutionary distance of Gnetopsida from Coniferopsida and Magnoliophyta is concluded to be decisively longer than the distance between Coniferopsida and Magnoliophyta, i.e., the former divergence corresponds to 286 Mya and the latter to 211 Mya. 相似文献
2.
For over 3 decades, the rate of replacement mutations has been assumed to be equal to, and estimated from, the rate of "strictly" neutral sequence divergence in noncoding regions and in silent-codon positions where mutations do not alter the amino acid encoded. This assumption is fundamental to estimating the fraction of harmful protein mutations and to identifying adaptive evolution at individual codons and proteins. We show that the assumption is not justifiable because a much larger fraction of codon positions is involved in hypermutable CpG dinucleotides as compared with the introns, leading to a higher expected replacement mutation rate per site in a vast majority of the genes. Consideration of this difference reveals a higher intensity of purifying natural selection than previously inferred in human genes. We also show that a much smaller number of genes are expected to be evolving with positive selection than that predicted using sequence divergence at intron and silent positions in the human genome. These patterns indicate the need for using new approaches for estimating rates of amino acid-altering mutations in order to find positively selected genes and codons in genomes that contain hypermutable CpG's. 相似文献
3.
Synonymous substitution rates in mitochondrial and nuclear genes of Drosophila were compared. To make accurate comparisons, we considered the following: (1) relative synonymous rates, which do not require
divergence time estimates, should be used; (2) methods estimating divergence should take into account base composition; (3)
only very closely related species should be used to avoid effects of saturation; (4) the heterogeneity of rates should be
examined. We modified the methods estimating synonymous substitution numbers to account for base composition bias. By using
these methods, we found that mitochondrial genes have 1.7–3.4 times higher synonymous substitution rates than the fastest
nuclear genes or 4.5–9.0 times higher rates than the average nuclear genes. The average rate of synonymous transversions was
2.7 (estimated from the melanogaster species subgroup) or 2.9 (estimated from the obscura group) times higher in mitochondrial genes than in nuclear genes. Synonymous transversions in mitochondrial genes occurred
at an approximately equivalent rate to those in the fastest nuclear genes. This last result is not consistent with the hypothesis
that the difference in turnover rates between mitochondrial and nuclear genomes is the major factor determining higher synonymous
substitution rates in mtDNA. We conclude that the difference in synonymous substitution rates is due to a combination of two
factors: a higher transitional mutation rate in mtDNA and constraints on nuclear genes due to selection for codon usage.
Received: 27 November 1996 / Accepted: 8 May 1997 相似文献
4.
Synonymous codons are not used at random, significantly influencing the base composition of the genome. The selection-mutation-drift model proposes that this bias reflects natural selection in favor of a subset of preferred codons. Previous estimates in Drosophila of the intensity of selective forces involved seem too large to be reconciled with theoretical predictions of the level of codon bias. This probably results from confounding effects of the demographic histories of the species concerned. We have studied three species of the virilis group of Drosophila, which are more likely to satisfy the assumptions of the evolutionary models. We analyzed the patterns of polymorphism and divergence in a sample of 18 genes and applied a new method for estimating the intensity of selection on synonymous mutations based on the frequencies of unpreferred mutations among polymorphic sites. This yielded estimates of selection intensities (N(e)s) of the order of 0.65, which is more compatible with the observed levels of codon bias. Our results support the action of both selection and mutational bias on codon usage bias and suggest that codon usage and genome base composition in the D. americana lineage are in approximate equilibrium. Biased gene conversion may also contribute to the observed patterns. 相似文献
5.
Since the birth of molecular evolutionary analysis,primates have been a central focus of study and mitochondrial DNA is well suited to these endeavors because of its unique features.Surprisingly,to date no comprehensive evaluation of the nucleotide substitution patterns has been conducted on the mitochondrial genome of primates.Here,we analyzed the evolutionary patterns and evaluated selection and recombination in the mitochondrial genomes of 44 Primates species downloaded from GenBank.The results revealed that a strong rate heterogeneity occurred among sites and genes in all comparisons.Likewise,an obvious decline in primate nucleotide diversity was noted in the subunit rRNAs and tRNAs as compared to the protein-coding genes.Within 13 protein-coding genes,the pattern of nonsynonymous divergence was similar to that of overall nucleotide divergence,while synonymous changes differed only for individual genes,indicating that the rate heterogeneity may result from the rate of change at nonsynonymous sites.Codon usage analysis revealed that there was intermediate codon usage bias in primate protein-coding genes,and supported the idea that GC mutation pressure might determine codon usage and that positive selection is not the driving force for the codon usage bias.Neutrality tests using site-specific positive selection from a Bayesian framework indicated no sites were under positive selection for any gene,consistent with near neutrality.Recombination tests based on the pairwise homoplasy test statistic supported complete linkage even for much older divergent primate species.Thus,with the exception of rate heterogeneity among mitochondrial genes,evaluating the validity assumed complete linkage and selective neutrality in primates prior to phylogenetic or phylogeographic analysis seems unnecessary. 相似文献
6.
Since the birth of molecular evolutionary analysis, primates have been a central focus of study and mitochondrial DNA is well suited to these endeavors because of its unique features. Surprisingly, to date no comprehensive evaluation of the nucleotide substitution patterns has been conducted on the mitochondrial genome of primates. Here, we analyzed the evolutionary patterns and evaluated selection and recombination in the mitochondrial genomes of 44 Primates species downloaded from GenBank. The results revealed that a strong rate heterogeneity occurred among sites and genes in all comparisons. Likewise, an obvious decline in primate nucleotide diversity was noted in the subunit rRNAs and tRNAs as compared to the protein-coding genes. Within 13 protein-coding genes, the pattern of nonsynonymous divergence was similar to that of overall nucleotide divergence, while synonymous changes differed only for individual genes, indicating that the rate heterogeneity may result from the rate of change at nonsynonymous sites. Codon usage analysis revealed that there was intermediate codon usage bias in primate protein-coding genes, and supported the idea that GC mutation pressure might determine codon usage and that positive selection is not the driving force for the codon usage bias. Neutrality tests using site-specific positive selection from a Bayesian framework indicated no sites were under positive selection for any gene, consistent with near neutrality. Recombination tests based on the pairwise homoplasy test statistic supported complete linkage even for much older divergent primate species. Thus, with the exception of rate heterogeneity among mitochondrial genes, evaluating the validity assumed complete linkage and selective neutrality in primates prior to phylogenetic or phylogeographic analysis seems unnecessary. 相似文献
7.
Codon usage in mammals is mainly determined by the spatial arrangement of genomic G + C-content, i.e., the isochore structure. Ancestral G + C-content at third codon positions of 27 nuclear protein-coding genes of eutherian mammals was estimated by maximum-likelihood analysis on the basis of a nonhomogeneous DNA substitution model, accounting for variable base compositions among present-day sequences. Data consistently supported a human-like ancestral pattern, i.e., highly variable G + C-content among genes. The mouse genomic structure-more narrow G + C-content distribution-would be a derived state. The circumstances of isochore evolution are discussed with respect to this result. A possible relationship between G + C-content homogenization in murid genomes and high mutation rate is proposed, consistent with the negative selection hypothesis for isochore maintenance in mammals. 相似文献
8.
Miyazawa S 《PloS one》2011,6(12):e28892
BACKGROUND: A mechanistic codon substitution model, in which each codon substitution rate is proportional to the product of a codon mutation rate and the average fixation probability depending on the type of amino acid replacement, has advantages over nucleotide, amino acid, and empirical codon substitution models in evolutionary analysis of protein-coding sequences. It can approximate a wide range of codon substitution processes. If no selection pressure on amino acids is taken into account, it will become equivalent to a nucleotide substitution model. If mutation rates are assumed not to depend on the codon type, then it will become essentially equivalent to an amino acid substitution model. Mutation at the nucleotide level and selection at the amino acid level can be separately evaluated. RESULTS: The present scheme for single nucleotide mutations is equivalent to the general time-reversible model, but multiple nucleotide changes in infinitesimal time are allowed. Selective constraints on the respective types of amino acid replacements are tailored to each gene in a linear function of a given estimate of selective constraints. Their good estimates are those calculated by maximizing the respective likelihoods of empirical amino acid or codon substitution frequency matrices. Akaike and Bayesian information criteria indicate that the present model performs far better than the other substitution models for all five phylogenetic trees of highly-divergent to highly-homologous sequences of chloroplast, mitochondrial, and nuclear genes. It is also shown that multiple nucleotide changes in infinitesimal time are significant in long branches, although they may be caused by compensatory substitutions or other mechanisms. The variation of selective constraint over sites fits the datasets significantly better than variable mutation rates, except for 10 slow-evolving nuclear genes of 10 mammals. An critical finding for phylogenetic analysis is that assuming variable mutation rates over sites lead to the overestimation of branch lengths. 相似文献
9.
To evaluate the relative importance of positive selection and neutral drift from the nucleotide base changes observed in
the homologous alignment of genes, a theoretical equation of base changes is formulated by including both the influence of
selection and the base substitutions due to mutations. Under the assumption that the average rate of base substitutions estimated
from synonymous changes is the ``true' mutation rate applicable at all positions, this method is applied to the vertebrate
globin gene family, and evaluates the departures of base change rates from the ``true' mutation rate at the first and second
codon positions as a consequence of preferential selection for the conservation of important function. In addition to the
strong effect of selection on the amino acid residues in the internal region mostly common to myoglobin and hemoglobin chains,
the distinctive directions of selective parameter values are seen at sites on the globin surface, distinguishing the subunit
contact residues of hemoglobins from the polar residues on the surface of myoglobins. Moreover, this effect of selection distinguishing
between the myoglobin and hemoglobin chain genes becomes weaker in cold-blooded vertebrates, especially in fish, strongly
suggesting the possibility that the clear distinction between these globins is a result of selection out of the changes regarded
as neutral ones in an ancestor of vertebrates. Thus, the present method may also serve to investigate the homology of many
other proteins from the aspect of molecular evolution, mainly focusing on the evolution of their biological functions.
Received: 2 January 1996 / Accepted: 20 February 1997 相似文献
10.
Most of the sophisticated methods to estimate evolutionary divergence between DNA sequences assume that the two sequences have evolved with the same pattern of nucleotide substitution after their divergence from their most recent common ancestor (homogeneity assumption). If this assumption is violated, the evolutionary distance estimated will be biased, which may result in biased estimates of divergence times and substitution rates, and may lead to erroneous branching patterns in the inferred phylogenies. Here we present a simple modification for existing distance estimation methods to relax the assumption of the substitution pattern homogeneity among lineages when analyzing DNA and protein sequences. Results from computer simulations and empirical data analyses for human and mouse genes are presented to demonstrate that the proposed modification reduces the estimation bias considerably and that the modified method performs much better than the LogDet methods, which do not require the homogeneity assumption in estimating the number of substitutions per site. We also discuss the relationship of the substitution and mutation rate estimates when the substitution pattern is not the same in the lineages leading to the two sequences compared. 相似文献
11.
Ellegren H 《Proceedings. Biological sciences / The Royal Society》2007,274(1606):1-10
Mutation has traditionally been considered a random process, but this paradigm is challenged by recent evidence of divergence rate heterogeneity in different genomic regions. One facet of mutation rate variation is the propensity for genetic change to correlate with the number of germ cell divisions, reflecting the replication-dependent origin of many mutations. Haldane was the first to connect this association of replication and mutation to the difference in the number of cell divisions in oogenesis (low) and spermatogenesis (usually high), and the resulting sex difference in the rate of mutation. The concept of male-biased mutation has been thoroughly analysed in recent years using an evolutionary approach, in which sequence divergence of autosomes and/or sex chromosomes are compared to allow inference about the relative contribution of mothers and fathers in the accumulation of mutations. For instance, assuming that a neutral sequence is analysed, that rate heterogeneity owing to other factors is cancelled out by the investigation of many loci and that the effect of ancestral polymorphism is properly taken into account, the male-to-female mutation rate ratio, alpham, can be solved from the observed difference in rate of X and Y chromosome divergence. The male mutation bias is positively correlated with the relative excess of cell divisions in the male compared to the female germ line, as evidenced by a generation time effect: in mammals, alpham is estimated at approximately 4-6 in primates, approximately 3 in carnivores and approximately 2 in small rodents. Another life-history correlate is sexual selection: when there is intense sperm competition among males, increased sperm production will be associated with a larger number of mitotic cell divisions in spermatogenesis and hence an increase in alpham. Male-biased mutation has implications for important aspects of evolutionary biology such as mate choice in relation to mutation load, sexual selection and the maintenance of genetic diversity despite strong directional selection, the tendency for a disproportionate large role of the X (Z) chromosome in post-zygotic isolation, and the evolution of sex. 相似文献
12.
Selection acting on codon usage can cause patterns of synonymous evolution to deviate considerably from those expected under neutrality. To investigate the quantitative relationship between parameters of mutation, selection, and demography, and patterns of synonymous site divergence, we have developed a novel combination of population genetic models and likelihood methods of phylogenetic sequence analysis. Comparing 50 orthologous gene pairs from Drosophila melanogaster and D. virilis and 27 from D. melanogaster and D. simulans, we show considerable variation between amino acids and genes in the strength of selection acting on codon usage and find evidence for both long-term and short-term changes in the strength of selection between species. Remarkably, D. melanogaster shows no evidence of current selection on codon usage, while its sister species D. simulans experiences only half the selection pressure for codon usage of their common ancestor. We also find evidence for considerable base asymmetries in the rate of mutation, such that the average synonymous mutation rate is 20-30% higher than in noncoding regions. A Bayesian approach is adopted to investigate how accounting for selection on codon usage influences estimates of the parameters of mutation. 相似文献
13.
In many biological systems, especially bacteria and unicellular eukaryotes, rates of synonymous and nonsynonymous nucleotide divergence are negatively correlated with the level of gene expression, a phenomenon that has been attributed to natural selection. Surprisingly, this relationship has not been examined in many important groups, including the unicellular model organism Chlamydomonas reinhardtii. Prior to this study, comparative data on protein-coding sequences from C. reinhardtii and its close noninterfertile relative C. incerta were very limited. We compiled and analyzed protein-coding sequences for 67 nuclear genes from these taxa; the sequences were mostly obtained from the C. reinhardtii EST database and our C. incerta EST data. Compositional and synonymous codon usage biases varied among genes within each species but were highly correlated between the orthologous genes of the two species. Relative rates of synonymous and nonsynonymous substitution across genes varied widely and showed a strong negative correlation with the level of gene expression estimated by the codon adaptation index. Our comparative analysis of substitution rates in introns of lowly and highly expressed genes suggests that natural selection has a larger contribution than mutation to the observed correlation between evolutionary rates and gene expression level in Chlamydomonas. 相似文献
14.
G B Golding 《Génome》1988,30(3):341-346
The divergence of immunoglobulin genes due to somatic mutation provides a natural example of DNA sequence divergence. This divergence was examined to gain insight into the processes of evolution and the determinants of the variance-to-mean ratio of sequence divergence. Normally, this ratio is found to be larger than expected (1.0 under Poisson assumptions) for the evolutionary divergence or most genes. Although not significantly less than one, all seven groups of immunoglobulin amino acid sequences have ratios smaller than expected, contrary to the evolutionary pattern generally observed. The substitutions in the immunoglobulin genes appear to be highly nonrandom and an excess of parallel changes (the major nonrandom feature of these mutations) is shown to cause smaller ratios. Because convergent or parallel mutations are often observed in the evolutionary divergence of genes, this suggests that forces causing the large observed ratios may actually have to be more powerful than previously expected. Further, since selection is one of the likely causes of parallel mutations, it should be noted that selection could significantly decrease the variance-to-mean ratio. The high frequency of parallel mutations and their resulting effects, as observed in the immunoglobulin genes, suggest that only poor inferences of sequence divergence can be made without actual knowledge of the ancestral sequence. 相似文献
15.
Selection promoting differential use of synonymous codons has been shown for several unicellular organisms and for Drosophila, but not for mammals. Selection coefficients operating on synonymous codons are likely to be extremely small, so that a very large effective population size is required for selection to overcome the effects of drift. In mammals, codon-usage bias is believed to be determined exclusively by mutation pressure, with differences between genes due to large-scale variation in base composition around the genome. The replication-dependent histone genes are expressed at extremely high levels during periods of DNA synthesis, and thus are among the most likely mammalian genes to be affected by selection on synonymous codon usage. We suggest that the extremely biased pattern of codon usage in the H3 genes is determined in part by selection. Silent site G + C content is much higher than expected based on flanking sequence G + C content, compared to other rodent genes with similar silent site base composition but lower levels of expression. Dinucleotide-mediated mutation bias does affect codon usage, but the affect is limited to the choice between G and C in some fourfold degenerate codons. Gene conversion between the two clusters of histone genes has not been an important force in the evolution of the H3 genes, but gene conversion appears to have had some effect within the cluster on chromosome 13. 相似文献
16.
In analyzing the silent nucleotide substitutions in some mammalian mitochondrial mRNA coding genes, we had found that the frequency of each of the four nucleotides in rat, mouse, and cow, but not in humans, is the same in the silent third codon position (Lanave C, Preparata G, Saccone C, Serio G (1984) J Mol Evol 20:86-93). Because our findings for these three species were compatible with a stationary Markov process for the evolution of nucleotide sequences, we applied such a model to calculate the effective evolutionary silent substitution rate (vs) and the divergence times among the species. In this paper we have analyzed the first and second codon positions in the same mammalian mitochondrial genes. We found that in the first and second codon positions the human mitochondrial genes satisfy the stationarity conditions. This has allowed us to use the stochastic model mentioned above to calculate the divergence times among mouse, rat, cow, and human. Furthermore, we have analyzed the silent substitution rate in one nuclear gene for these four mammals. We found that in this gene the effective silent substitution rate is about 3 times lower than in mitochondrial genes, and that humans are in this case stationary with respect to the other three mammals in the third codon position as well. Application of our Markov model to this latter gene yields divergence times consistent with our previous determinations. 相似文献
17.
Murid rodents show much less variation in isochore base composition than do most other mammals, a difference which has been
referred to as the murid shift. We have investigated the murid shift by asking (1) whether the murid shift is ongoing and
(2) whether there is any evidence of selection or biased gene conversion affecting base composition in the present-day mouse
genome. By estimating the ancestral base composition of protein-coding genes in murids we can confirm that the murid shift
is ongoing. Tests using nongenic polymorphism data fail to reject the hypothesis that base composition is due to mutation
bias alone. However, the patterns of compositional change suggested by the polymorphism and divergence data differ, suggesting
the possibility of two murid shifts. 相似文献
18.
Functional shifts during protein evolution are expected to yield shifts in substitution rate, and statistical methods can test for this at both codon and amino acid levels. Although methods based on models of sequence evolution serve as powerful tools for studying evolutionary processes, violating underlying assumptions can lead to false biological conclusions. It is not unusual for functional shifts to be accompanied by changes in other aspects of the evolutionary process, such as codon or amino acid frequencies. However, models used to test for functional divergence assume these frequencies remain constant over time. We employed simulation to investigate the impact of non-stationary evolution on functional divergence inference. We investigated three likelihood ratio tests based on codon models and found varying degrees of sensitivity. Joint effects of shifts in frequencies and selection pressures can be large, leading to false signals for positive selection. Amino acid-based tests (FunDi and Bivar) were also compromised when several aspects of the substitution process were not adequately modeled. We applied the same tests to a core genome “scan” for functional divergence between light-adapted ecotypes of the cyanobacteria Prochlorococcus, and carried out gene-specific simulations for ten genes. Results of those simulations illustrated how the inference of functional divergence at the genomic level can be seriously impacted by model misspecification. Although computationally costly, simulations motivated by data in hand are warranted when several aspects of the substitution process are either misspecified or not included in the models upon which the statistical tests were built. 相似文献
19.
Cecilia Lanave Giuliano Preparata Cecilia Saccone 《Journal of molecular evolution》1985,21(4):346-350
Summary In analyzing the silent nucleotide substitutions in some mammalian mitochondrial mRNA coding genes, we had found that the frequency of each of the four nucleotides in rat, mouse, and cow, but not in humans, is the same in the silent third codon position (Lanave C, Preparata G, Saccone C, Serio G (1984) J Mol Evol 20:86-93). Because our findings for these three species were compatible with a stationary Markov process for the evolution of nucleotide sequences, we applied such a model to calculate the effective evolutionary silent substitution rate (vs) and the divergence times among the species. In this paper we have analyzed the first and second codon positions in the same mammalian mitochondrial genes. We found that in the first and second codon positions the human mitochondrial genes satisfy the stationarity conditions. This has allowed us to use the stochastic model mentioned above to calculate the divergence times among mouse, rat, cow, and human. Furthermore, we have analyzed the silent substitution rate in one nuclear gene for these four mammals. We found that in this gene the effective silent substitution rate is about 3 times lower than in mitochondrial genes, and that humans are in this case stationary with respect to the other three mammals in the third codon position as well. Application of our Markov model to this latter gene yields divergence times consistent with our previous determinations. 相似文献