共查询到20条相似文献,搜索用时 31 毫秒
1.
Fernando Alvarez-Valin Kamel Jabbari Nicolas Carels Giorgio Bernardi 《Journal of molecular evolution》1999,49(3):330-342
In this work, we have investigated the relationships between synonymous and nonsynonymous rates and base composition in coding
sequences from Gramineae to analyze the factors underlying the variation in substitutional rates. We have shown that in these genes the rates of nucleotide
divergence, both synonymous and nonsynonymous, are, to some extent, dependent on each other and on the base composition. In
the first place, the variation in nonsynonymous rate is related to the GC level at the second codon position (the higher the
GC2 level, the higher the amino acid replacement rate). The correlation is especially strong with T2, the coefficients being significant in the three data sets analyzed. This correlation between nonsynonymous rate and base
composition at the second codon position is also detectable at the intragenic level, which implies that the factors that tend
to increase the intergenic variance in nonsynonymous rates also affect the intragenic variance. On the other hand, we have
shown that the synonymous rate is strongly correlated with the GC3 level. This correlation is observed both across genes and at the intragenic level. Similarly, the nonsynonymous rate is also
affected at the intragenic level by GC3 level, like the silent rate. In fact, synonymous and nonsynonymous rates exhibit a parallel behavior in relation to GC3 level, indicating that the intragenic patterns of both silent and amino acid divergence rates are influenced in a similar
way by the intragenic variation of GC3. This result, taken together with the fact that the number of genes displaying intragenic correlation coefficients between
synonymous and nonsynonymous rates is not very high, but higher than random expectation (in the three data sets analyzed),
strongly suggests that the processes of silent and amino acid replacement divergence are, at least in part, driven by common
evolutionary forces in genes from Gramineae.
Received: 2 July 1998 / Accepted: 18 April 1999 相似文献
2.
There are two tightly linked loci (D and CE) for the human Rh blood group. Their gene products are membrane proteins having
12 transmembrane domains and form a complex with Rh50 glycoprotein on erythrocytes. We constructed phylogenetic networks of
human and nonhuman primate Rh genes, and the network patterns suggested the occurrences of gene conversions. We therefore
used a modified site-by-site reconstruction method by using two assumed gene trees and detected 9 or 11 converted regions.
After eliminating the effect of gene conversions, we estimated numbers of nonsynonymous and synonymous substitutions for each
branch of both trees. Whichever gene tree we selected the branch connecting hominoids and Old World monkeys showed significantly
higher nonsynonymous than synonymous substitutions, an indication of positive selection. Many other branches also showed higher
nonsynonymous than synonymous substitutions; this suggests that the Rh genes have experienced some kind of positive selection.
Received: 16 March 1999 / Accepted: 17 June 1999 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 and nonsynonymous rate variation in nuclear genes of mammals 总被引:34,自引:6,他引:28
A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes
from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure,
transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the
constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the
48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result
provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and
nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The
differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate
bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates,
and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise
sequence comparison, because more-realistic models about the mutation and substitution processes can be incorporated in the
analysis.
Received: 17 May 1997 / Accepted: 28 September 1997 相似文献
5.
Fernando Alvarez-Valin Kamel Jabbari Giorgio Bernardi 《Journal of molecular evolution》1998,46(1):37-44
Previous investigations indicated that synonymous and nonsynonymous substitution rates are correlated in mammalian genes.
In the present work, this correlation has been studied at the intragenic level using a dataset of 48 orthologous genes from
species belonging to at least four different mammalian orders. The results obtained show that the intragenic variability in
synonymous rates is correlated with that of nonsynonymous rates. Moreover, the variation in GC level (and especially of C
level) of silent positions along each gene is correlated with the variation in synonymous rate. These results reinforce the
previous conclusions that synonymous and nonsynonymous rates as well as GC levels of silent positions are to some extent under
common selective constraints.
Received: 10 July 1997 / Accepted: 13 August 1997 相似文献
6.
Weinreich DM 《Journal of molecular evolution》2001,52(1):40-50
A higher rate of molecular evolution in rodents than in primates at synonymous sites and, to a lesser extent, at amino acid
replacement sites has been reported previously for most nuclear genes examined. Thus in these genes the average ratio of amino
acid replacement to synonymous substitution rates in rodents is lower than in primates, an observation at odds with the neutral
model of molecular evolution. Under Ohta's mildly deleterious model of molecular evolution, these observations are seen as
the consequence of the combined effects of a shorter generation time (driving a higher mutation rate) and a larger effective
population size (resulting in more effective selection against mildly deleterious mutations) in rodents. The present study
reports the results of a maximum-likelihood analysis of the ratio of amino acid replacements to synonymous substitutions for
genes encoded in mitochondrial DNA (mtDNA) in these two lineages. A similar pattern is observed: in rodents this ratio is
significantly lower than in primates, again consistent only with the mildly deleterious model. Interestingly the lineage-specific
difference is much more pronounced in mtDNA-encoded than in nuclear-encoded proteins, an observation which is shown to run
counter to expectation under Ohta's model. Finally, accepting certain fossil divergence dates, the lineage-specific difference
in amino acid replacement-to-synonymous substitution ratio in mtDNA can be partitioned and is found to be entirely the consequence
of a higher mutation rate in rodents. This conclusion is consistent with a replication-dependent model of mutation in mtDNA.
Received: 24 September 1999 / Accepted: 18 September 2000 相似文献
7.
Rates of Conservative and Radical Nonsynonymous Nucleotide Substitutions in Mammalian Nuclear Genes 总被引:28,自引:0,他引:28
Zhang J 《Journal of molecular evolution》2000,50(1):56-68
To understand the process and mechanism of protein evolution, it is important to know what types of amino acid substitutions
are more likely to be under selection and what types are mostly neutral. An amino acid substitution can be classified as either
conservative or radical, depending on whether it involves a change in a certain physicochemical property of the amino acid.
Assuming Kimura's two-parameter model of nucleotide substitution, I present a method for computing the numbers of conservative
and radical nonsynonymous (amino acid altering) nucleotide substitutions per site and estimate these rates for 47 nuclear
genes from mammals. The results are as follows. (1) The average radical/conservative rate ratio is 0.81 for charge changes,
0.85 for polarity changes, and 0.49 when both polarity and volume changes are considered. (2) The radical/conservative rate
ratio is positively correlated with the nonsynonymous/synonymous rate ratio for charge changes or when both polarity and volume
changes are considered. (3) Both the conservative/synonymous rate ratio and the radical/synonymous rate ratio are lower in
the rodent lineage than in the primate or artiodactyl lineage, suggesting more intense purifying selection in the rodent lineage,
for both conservative and radical nonsynonymous substitutions. (4) Neglecting transition/transversion bias would cause an
underestimation of both radical and conservative rates and the ratio thereof. (5) Transversions induce more dramatic genetic
alternations than transitions in that transversions produce more amino acid altering changes and among which, more radical
changes.
Received: 6 April 1999 / Accepted: 16 August 1999 相似文献
8.
Nucleotide Substitution Rate of Mammalian Mitochondrial Genomes 总被引:22,自引:0,他引:22
We present here for the first time a comprehensive study based on the analysis of closely related organisms to provide an
accurate determination of the nucleotide substitution rate in mammalian mitochondrial genomes. This study examines the evolutionary
pattern of the different functional mtDNA regions as accurately as possible on the grounds of available data, revealing some
important ``genomic laws.' The main conclusions can be summarized as follows. (1) High intragenomic variability in the evolutionary
dynamic of mtDNA was found. The substitution rate is strongly dependent on the region considered, and slow- and fast-evolving
regions can be identified. Nonsynonymous sites, the D-loop central domain, and tRNA and rRNA genes evolve much more slowly
than synonymous sites and the two peripheral D-loop region domains. The synonymous rate is fairly uniform over the genome,
whereas the rate of nonsynonymous sites depends on functional constraints and therefore differs considerably between genes.
(2) The commonly accepted statement that mtDNA evolves more rapidly than nuclear DNA is valid only for some regions, thus
it should be referred to specific mitochondrial components. In particular, nonsynonymous sites show comparable rates in mitochondrial
and nuclear genes; synonymous sites and small rRNA evolve about 20 times more rapidly and tRNAs about 100 times more rapidly
in mitochondria than in their nuclear counterpart. (3) A species-specific evolution is particularly evident in the D-loop
region. As the divergence times of the organism pairs under consideration are known with sufficient accuracy, absolute nucleotide
substitution rates are also provided.
Received: 11 May 1998 / Accepted: 2 September 1998 相似文献
9.
To characterize the coding-sequence divergence of closely related genomes, we compared DNA sequence divergence between sequences
from a Brassica rapa ssp. pekinensis EST library isolated from flower buds and genomic sequences from Arabidopsis thaliana. The specific objectives were (i) to determine the distribution of and relationship between K
a and K
s, (ii) to identify genes with the lowest and highest K
a:K
s values, and (iii) to evaluate how codon usage has diverged between two closely related species. We found that the distribution
of K
a:K
s was unimodal, and that substitution rates were more variable at nonsynonymous than synonymous sites, and detected no evidence
that K
a and K
s were positively correlated. Several genes had K
a:K
s values equal to or near zero, as expected for genes that have evolved under strong selective constraint. In contrast, there
were no genes with K
a:K
s >1 and thus we found no strong evidence that any of the 218 sequences we analyzed have evolved in response to positive selection.
We detected a stronger codon bias but a lower frequency of GC at synonymous sites in A. thaliana than B. rapa. Moreover, there has been a shift in the profile of most commonly used synonymous codons since these two species diverged
from one another. This shift in codon usage may have been caused by stronger selection acting on codon usage or by a shift
in the direction of mutational bias in the B. rapa phylogenetic lineage. 相似文献
10.
Rates of synonymous and nonsynonymous nucleotide substitutions and codon usage bias (ENC) were estimated for a number of
nuclear and chloroplast genes in a sample of centric and pennate diatoms. The results suggest that DNA evolution has taken
place, on an average, at a slower rate in the chloroplast genes than in the nuclear genes: a rate variation pattern similar
to that observed in land plants. Synonymous substitution rates in the chloroplast genes show a negative association with the
degree of codon usage bias, suggesting that genes with a higher degree of codon usage bias have evolved at a slower rate.
While this relationship has been shown in both prokaryotes and multicellular eukaryotes, it has not been demonstrated before
in diatoms.
Received: 3 June 1998 / Accepted: 11 August 1998 相似文献
11.
A Survey of the Molecular Evolutionary Dynamics of Twenty-Five Multigene Families from Four Grass Taxa 总被引:10,自引:0,他引:10
We surveyed the molecular evolutionary characteristics of 25 plant gene families, with the goal of better understanding general
processes in plant gene family evolution. The survey was based on 247 GenBank sequences representing four grass species (maize,
rice, wheat, and barley). For each gene family, orthology and paralogy relationships were uncertain. Recognizing this uncertainty,
we characterized the molecular evolution of each gene family in four ways. First, we calculated the ratio of nonsynonymous
to synonymous substitutions (d
N/d
S) both on branches of gene phylogenies and across codons. Our results indicated that the d
N/d
S ratio was statistically heterogeneous across branches in 17 of 25 (68%) gene families. The vast majority of d
N/d
S estimates were <<1.0, suggestive of selective constraint on amino acid replacements, and no estimates were >1.0, either across
phylogenetic lineages or across codons. Second, we tested separately for nonsynonymous and synonymous molecular clocks. Sixty-eight
percent of gene families rejected a nonsynonymous molecular clock, and 52% of gene families rejected a synonymous molecular
clock. Thus, most gene families in this study deviated from clock-like evolution at either synonymous or nonsynonymous sites.
Third, we calculated the effective number of codons and the proportion of G+C synonymous sites for each sequence in each gene
family. One or both quantities vary significantly within 18 of 25 gene families. Finally, we tested for gene conversion, and
only six gene families provided evidence of gene conversion events. Altogether, evolution for these 25 gene families is marked
by selective constraint that varies among gene family members, a lack of molecular clock at both synonymous and nonsynonymous
sites, and substantial variation in codon usage.
Received: 25 May 2000 / Accepted: 16 October 2000 相似文献
12.
Molecular evolution of nitrate reductase genes 总被引:9,自引:0,他引:9
To understand the evolutionary mechanisms and relationships of nitrate reductases (NRs), the nucleotide sequences encoding
19 nitrate reductase (NR) genes from 16 species of fungi, algae, and higher plants were analyzed. The NR genes examined show
substantial sequence similarity, particularly within functional domains, and large variations in GC content at the third codon
position and intron number. The intron positions were different between the fungi and plants, but conserved within these groups.
The overall and nonsynonymous substitution rates among fungi, algae, and higher plants were estimated to be 4.33 × 10−10 and 3.29 × 10−10 substitutions per site per year. The three functional domains of NR genes evolved at about one-third of the rate of the N-terminal
and the two hinge regions connecting the functional domains. Relative rate tests suggested that the nonsynonymous substitution
rates were constant among different lineages, while the overall nucleotide substitution rates varied between some lineages.
The phylogenetic trees based on NR genes correspond well with the phylogeny of the organisms determined from systematics and
other molecular studies. Based on the nonsynonymous substitution rate, the divergence time of monocots and dicots was estimated
to be about 340 Myr when the fungi–plant or algae–higher plant divergence times were used as reference points and 191 Myr
when the rice–barley divergence time was used as a reference point. These two estimates are consistent with other estimates
of divergence times based on these reference points. The lack of consistency between these two values appears to be due to
the uncertainty of the reference times.
Received: 10 April 1995 / Accepted: 10 September 1995 相似文献
13.
Jonathan E. Boyson Kristen K. Iwanaga Julie A. Urvater Austin L. Hughes Thaddeus G. Golos D. I. Watkins 《Immunogenetics》1999,49(2):86-98
HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecule that is expressed only in the human placenta,
suggesting that it plays an important role at the fetal-maternal interface. In rhesus monkeys, which have similar placentation
to humans, the HLA-G orthologue is a pseudogene. However, rhesus monkeys express a novel placental MHC class I molecule, Mamu-AG, which has HLA-G-like
characteristics. Phylogenetic analysis of AG alleles in two Old World primate species, the baboon and the rhesus macaque, revealed limited diversity characteristic of
a nonclassical MHC class I locus. Gene trees constructed using classical and nonclassical primate MHC class I alleles demonstrated
that the AG locus was most closely related to the classical A locus. Interestingly, gene tree analyses suggested that the AG alleles were most closely related to a subset of A alleles which are the products of an ancestral interlocus recombination event between the A and B loci. Calculation of the rates of synonymous and nonsynonymous substitution at the AG locus revealed that positive selection was not acting on the codons encoding the peptide binding region. In exon 4, however,
the rate of nonsynonymous substitution was significantly lower than the rate of synonymous substitution, suggesting that negative
selection was acting on these codons.
Received: 22 April 1998 / Revised: 15 July 1998 相似文献
14.
To determine whether the persistent nature of hepatitis C infection is related to the emergence of antigenic variants driven
by immune selection, we examined the sequence heterogeneity in a portion of the hepatitis C virus (HCV) nonstructural 3 (NS3)
gene of a patient infected over the course of more than 2 years. By PCR amplification, cloning, and sequencing, we observed
several variable and conserved regions in the NS3 segment of the HCV genome. All variable regions had higher ratios of nonsynonymous/synonymous
mutations and encompassed immunodominant epitopes, and their locations were not essential to maintain the known function of
HCV RNA helicase. In contrast, the regions that are critical for HCV RNA helicase activity were found to be conserved with
lower heterogeneity or lower ratios of nonsynonymous/synonymous mutations, and none except one of these regions was encoded
within immunodominant epitopes. Our results are consistent with immune selection of viral variants at the epitope and molecular
levels that may enable HCV to evade host defenses over time. Plotting the relatedness of sequence variants revealed a star
topology suggesting that a wild-type HCV sequence is maintained, unlike HIV.
Received: 2 November 2000 / Accepted: 1 October 2001 相似文献
15.
We have investigated patterns of within-species polymorphism and between-species divergence for synonymous and nonsynonymous variants at a set of autosomal and X-linked loci of Drosophila miranda. D. pseudoobscura and D. affinis were used for the between-species comparisons. The results suggest the action of purifying selection on nonsynonymous, polymorphic variants. Among synonymous polymorphisms, there is a significant excess of synonymous mutations from preferred to unpreferred codons and of GC to AT mutations. There was no excess of GC to AT mutations among polymorphisms at noncoding sites. This suggests that selection is acting to maintain the use of preferred codons. Indirect evidence suggests that biased gene conversion in favor of GC base pairs may also be operating. The joint intensity of selection and biased gene conversion, in terms of the product of effective population size and the sum of the selection and conversion coefficients, was estimated to be approximately 0.65. 相似文献
16.
Singhania NA Dyer KD Zhang J Deming MS Bonville CA Domachowske JB Rosenberg HF 《Journal of molecular evolution》1999,49(6):721-728
The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase
3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs
of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of
eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine
counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have
occurred at these loci recently, sometime after the divergence of these two rodent species (∼10–15 million years ago). Nonsynonymous
substitutions per site (d
N) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated
rates, and comparisons of nonsynonymous to synonymous substitution (d
N / d
S) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures
promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain,
our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense.
Received: 8 April 1999 / Accepted: 22 June 1999 相似文献
17.
de Miranda AB Alvarez-Valin F Jabbari K Degrave WM Bernardi G 《Journal of molecular evolution》2000,50(1):45-55
Mycobacterium tuberculosis and Mycobacterium leprae are the ethiological agents of tuberculosis and leprosy, respectively. After performing extensive comparisons between genes
from these two GC-rich bacterial species, we were able to construct a set of 275 homologous genes. Since these two bacterial
species also have a very low growth rate, translational selection could not be so determinant in their codon preferences as
it is in other fast-growing bacteria. Indeed, principal-components analysis of codon usage from this set of homologous genes
revealed that the codon choices in M. tuberculosis and M. leprae are correlated not only with compositional constraints and translational selection, but also with the degree of amino acid
conservation and the hydrophobicity of the encoded proteins. Finally, significant correlations were found between GC3 and synonymous distances as well as between synonymous and nonsynonymous distances.
Received: 30 October 1998 / Accepted: 16 August 1999 相似文献
18.
Amino acid replacements in the peptide-binding region (PBR) of the functional major histocompatibility complex (Mhc) genes appear to be driven by balancing selection. Of the various types of balancing selection, we have examined a model equivalent to overdominance that confers heterozygote advantage. As discussed by A. Robertson, overdominance selection tends to maintain alleles that have more or less the same degree of heterozygote advantage. Because of this symmetry, the model makes various testable predictions about the genealogical relationships among different alleles and provides ways of analyzing DNA sequences of Mhc alleles. In this paper, we analyze DNA sequences of 85 alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci with respect to the number of alleles and extent of nucleotide differences at the PBR, as well as at the synonymous (presumably neutral) sites. Theory suggests that the number of alleles that differ at the sites targeted by selection (presumably the nonsynonymous sites in the PBR) should be equal to the mean number of nucleotide substitutions among pairs of alleles. We also demonstrate that the nucleotide substitution rate at the targeted sites relative to that of neutral sites may be much larger than 1. The predictions of the presented model are in surprisingly good agreement with the actual data and thus provide means for inferring certain population parameters. For overdominance selection in a finite population at equilibrium, the product of selection intensity (s) against homozygotes and the effective population size (N) is estimated to be 350-3000, being largest at the B locus and smallest at the C locus. We argue that N is of the order of 10(5) and s is several percent at most, if the mutation rate per site per generation is 10(-8). 相似文献
19.
A fractal renewal point process (FRPP) is used to model molecular evolution in agreement with the relationship between the
variance and the mean numbers of nonsynonymous and synonymous substitutions in mammals. Like other episodic models such as
the doubly stochastic Poisson process, this model accounts for the large variances observed in amino acid substitution rates,
but unlike certain other episodic models, it also accounts for the increase in the index of dispersion with the mean number
of substitutions in Ohta's (1995) data. We find that this correlation is significant for nonsynonymous substitutions at the
1% level and for synonymous substitutions at the 10% level, even after removing lineage effects and when using Bulmer's (1989)
unbiased estimator of the index of dispersion. This model is simpler than most other overdispersed models of evolution in
the sense that it is fully specified by a single interevent probability distribution. Interpretations in terms of chaotic
dynamics and in terms of chance and selection are discussed.
Received: 12 January 1998 / Accepted: 19 May 1998 相似文献
20.
Natural selection favors certain synonymous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persist. We use the frequency distributions of synonymous polymorphisms
to test three hypotheses for the existence of translationally sub-optimal codons: (1) selection is a relatively weak force,
so there is a balance between mutation, selection, and drift; (2) at some sites there is no selection on codon usage, so some
synonymous sites are unaffected by translational selection; and (3) translationally sub-optimal codons are favored by alternative
selection pressures at certain synonymous sites. We find that when all the data is considered, model 1 is supported and both
models 2 and 3 are rejected as sole explanations for the existence of translationally sub-optimal codons. However, we find
evidence in favor of both models 2 and 3 when the data is partitioned between groups of amino acids and between regions of
the genes. Thus, all three mechanisms appear to contribute to the existence of translationally sub-optimal codons in E. coli.
Received: 18 July 2000 / Accepted: 17 April 2001 相似文献