首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Proteins evolve under a myriad of biophysical selection pressures that collectively control the patterns of amino acid substitutions. These evolutionary pressures are sufficiently consistent over time and across protein families to produce substitution patterns, summarized in global amino acid substitution matrices such as BLOSUM, JTT, WAG, and LG, which can be used to successfully detect homologs, infer phylogenies, and reconstruct ancestral sequences. Although the factors that govern the variation of amino acid substitution rates have received much attention, the influence of thermodynamic stability constraints remains unresolved. Here we develop a simple model to calculate amino acid substitution matrices from evolutionary dynamics controlled by a fitness function that reports on the thermodynamic effects of amino acid mutations in protein structures. This hybrid biophysical and evolutionary model accounts for nucleotide transition/transversion rate bias, multi‐nucleotide codon changes, the number of codons per amino acid, and thermodynamic protein stability. We find that our theoretical model accurately recapitulates the complex yet universal pattern observed in common global amino acid substitution matrices used in phylogenetics. These results suggest that selection for thermodynamically stable proteins, coupled with nucleotide mutation bias filtered by the structure of the genetic code, is the primary driver behind the global amino acid substitution patterns observed in proteins throughout the tree of life.  相似文献   

2.
Routine electrophoretic surveys for genetic variation in natural populations depend primarily upon detecting differences in the net charge carried by a protein. We have calculated the proportion of base substitutions which would yield an electrophoretically detectable mutant protein, and the relative mutation rates among different chare classes, under a variety of simplifying assumptions. These calculations indicate that: (i) only 25 per cent of all single base mutations would lead to a charge change on a protein molecule. (ii) five distinct classes of electrophoretic variants can be generated from a specified protein by single base substitutions. (iii) the relative mutation rates differ markedly among the different charge classes which can be generated by single base substitutions. The estimates of the proportion of electrophoretically detectable mutant proteins and relative mutation rates among charge classes were relatively robust to changes in assumptions concerned with the kind and site of base substitutions and the amino acid composition of the protein.  相似文献   

3.
E. Zouros 《Genetics》1979,92(2):623-646
A method is presented for estimating relative mutation rates or relative effective population sizes, under the hypothesis of adaptively neutral allelic variation. This method was applied to seven surveys of electrophoretic variation. It was observed that electrophoretic mutation rates so obtained follow the gamma distribution and, in Drosophila, are positively correlated with the molecular weights of the enzymes subunits. The variance in mutation rate is larger under the step-wise model of electrophoretic mutation than under the infinite-alleles model. Rates for the most variable loci may exceed rates for less variable loci by a factor of 500. For completely invariant loci, this factor may be as high as 4 X 10(4), an observation suggesting that these loci are subject to purifying selection. In contrast to mutation rates, effective population sizes may vary at the most by a factor of ten. These results support the hypothesis that differences in the amount of electrophoretic variability among polymorphic loci may reflect differences in the rate by which electrophoretically detectable variation is generated in population.  相似文献   

4.
Summary Based on the rates of synonymous substitution in 42 protein-codin gene pairs from rat and human, a correlation is shown to exist between the frequency of the nucleotides in all positions of the codon and the synonymous substitution rate. The correlation coefficients were positive for A and T and negative for C and G. This means that AT-rich genes accumulate more synonymous substitutions than GC-rich genes. Biased patterns of mutation could not account for this phenomenon. Thus, the variation in synonymous substitution rates and the resulting unequal codon usage must be the consequence of selection against A and T in synonymous positions. Most of the varition in rates of synonymous substitution can be explained by the nucleotide composition in synonymous positions. Codon-anticodon interactions, dinucleotide frequencies, and contextual factors influence neither the rates of synonymous substitution nor codon usage. Interestingly, the nucleotide in the second position of codons (always a nonsynonymous position) was found to affect the rate of synonymous substitution. This finding links the rate of nonsynonymous substitution with the synonymous rate. Consequently, highly conservative proteins are expected to be encoded by genes that evolve slowly in terms of synonymous substitutions, and are consequently highly biased in their codon usage.  相似文献   

5.
Gene duplication and loss are predicted to be at least of the order of the substitution rate and are key contributors to the development of novel gene function and overall genome evolution. Although it has been established that proteins evolve more rapidly after gene duplication, we were interested in testing to what extent this reflects causation or association. Therefore, we investigated the rate of evolution prior to gene duplication in chordates. Two patterns emerged; firstly, branches, which are both preceded by a duplication and followed by a duplication, display an elevated rate of amino acid replacement. This is reflected in the ratio of nonsynonymous to synonymous substitution (mean nonsynonymous to synonymous nucleotide substitution rate ratio [Ka:Ks]) of 0.44 compared with branches preceded by and followed by a speciation (mean Ka:Ks of 0.23). The observed patterns suggest that there can be simultaneous alteration in the selection pressures on both gene duplication and amino acid replacement, which may be consistent with co-occurring increases in positive selection, or alternatively with concurrent relaxation of purifying selection. The pattern is largely, but perhaps not completely, explained by the existence of certain families that have elevated rates of both gene duplication and amino acid replacement. Secondly, we observed accelerated amino acid replacement prior to duplication (mean Ka:Ks for postspeciation preduplication branches was 0.27). In some cases, this could reflect adaptive changes in protein function precipitating a gene duplication event. In conclusion, the circumstances surrounding the birth of new proteins may frequently involve a simultaneous change in selection pressures on both gene-copy number and amino acid replacement. More precise modeling of the relative importance of preduplication, postduplication, and simultaneous amino acid replacement will require larger and denser genomic data sets from multiple species, allowing simultaneous estimation of lineage-specific fluctuations in mutation rates and adaptive constraints.  相似文献   

6.
An alternative approach for plant complex protein extracts pre-purification by in-solution isoelectric focusing in non-denaturing conditions is presented. The separation of biologically active proteins, in narrow ranges of isoelectric point (pI) was obtained by a modified OFFGEL electrophoresis. Two different water-soluble protein extracts from Phragmites leaves were fractionated into 24 fractions within a 3–10 pI range at 10 °C in the absence of denaturing/reducing agents. One-dimensional electrophoretic analysis revealed different protein distribution patterns and the effective fractionation of both protein extracts. Peroxidase activity of each fraction confirmed that proteins remained active and pre-purification occurred. Biological triplicates assured the needed reproducibility.  相似文献   

7.
Herbeck JT  Funk DJ  Degnan PH  Wernegreen JJ 《Genetics》2003,165(4):1651-1660
The obligate endosymbiotic bacterium Buchnera aphidicola shows elevated rates of sequence evolution compared to free-living relatives, particularly at nonsynonymous sites. Because Buchnera experiences population bottlenecks during transmission to the offspring of its aphid host, it is hypothesized that genetic drift and the accumulation of slightly deleterious mutations can explain this rate increase. Recent studies of intraspecific variation in Buchnera reveal patterns consistent with this hypothesis. In this study, we examine inter- and intraspecific nucleotide variation in groEL, a highly conserved chaperonin gene that is constitutively overexpressed in Buchnera. Maximum-likelihood estimates of nonsynonymous substitution rates across Buchnera species are strikingly low at groEL compared to other loci. Despite this evidence for strong purifying selection on groEL, our intraspecific analysis of this gene documents reduced synonymous polymorphism, elevated nonsynonymous polymorphism, and an excess of rare alleles relative to the neutral expectation, as found in recent studies of other Buchnera loci. Comparisons with Escherichia coli generally show patterns predicted by their differences in N(e). The sum of these observations is not expected under relaxed or balancing selection, selective sweeps, or increased mutation rate. Rather, they further support the hypothesis that drift is an important force driving accelerated protein evolution in this obligate mutualist.  相似文献   

8.
Mitochondrial genomes encode fundamental subunits of the basic energy producing machinery of eukaryotic cells that are under strong functional constraint. Paradoxically, these genes evolve rapidly in general, and there is substantial variation in evolutionary rates among genes within genomes. In order to investigate spatial variation in selection intensity, we conducted tests of neutrality using ratios of synonymous to nonsynonymous substitutions (dN/dS = omega) on numerous protein gene segments from fishes and mammals. Values of omega were very low for nearly all genomic regions. However, values of both omega and dN varied in a clinal pattern with increasing distance from the light-strand origin of replication. Spatial heterogeneity of nonsynonymous substitution rates exhibits a significantly positive correlation with variation in mutation rates that are related to the mode of mitochondrial DNA replication. The finding that nonsynonymous substitution rates are proportional to mutation rates is expected if a majority of substitutions are selectively neutral or slightly deleterious. Spatial patterns of among-gene variation in nonsynonymous rates were highly similar between fishes and mammals, suggesting that forces governing mitochondrial gene evolution have remained relatively constant over 450 Myr of vertebrate evolution. Conservation of substitution patterns despite major shifts in thermal habit and metabolic demands among taxa implicates a conserved replication mechanism controlling relative mutation rates as a major determinant of mitochondrial protein evolution.  相似文献   

9.
George B. Johnson 《Genetics》1976,83(1):149-167
By varying polyacrylamide gel pore size, the alpha-glycerophosphate dehydrogenase locus of Colias butterflies is shown to contain at least five alkeles, rather than the two which had been reported previously. Two of the alleles have the same apparent net charge, and presumably are detected electrophoretically because of the conformational differences. Additional variation occurs in the isoelectric points of the proteins. It is suggested that electrophoresis employing a single gel of intermediated pore size will fail to discriminate between many alleles, and that the concept of electrophoretic alleles as differing simply in charge may not always be appropriate.  相似文献   

10.
Isoallele Frequencies in Very Large Populations   总被引:5,自引:3,他引:2       下载免费PDF全文
Jack Lester King 《Genetics》1974,76(3):607-613
The frequencies of electrophoretically distinguishable allelic forms of enzymes may be very different from the corresponding frequencies of structurally distinct forms, because many sequence variants may have identical electrophoretic charge. In large populations such frequencies will be determined largely by the number of amino acid sites that are free to vary. The number of distinguishable electrophoretic variants will remain fairly small. Beyond some limiting size, no further effect of population size on allele frequencies is expected, so isolated large populations will have closely similar allele frequencies if polymorphism is due largely to mutation and drift. The most common electrophoretic alleles are expected to be flanked by the next most common, with the rarer alleles increasingly distal. Neither strong selection nor mutation/drift interpretations of enzyme polymorphism are yet disproven, nor is any point between these extremes.  相似文献   

11.
Genetic polymorphism of human plasma apolipoprotein A-IV has been detected by isoelectric focusing techniques followed by immunoblotting. The molecular basis for this apoA-IV polymorphism has been elucidated. Analysis of the protein coding sequences of the apoA-IV alleles 1 and 2 revealed a single G to T substitution in the apoA-IV-2 allele. The point mutation, occurring in a region highly conserved among the mouse, rat, and human A-IV apolipoproteins, converts the glutamine at position 360 of the mature protein to a histidine. This amino acid substitution adds one positive charge unit to the apoA-IV-1 isoprotein (pI 4.97) thus creating the more basic apoA-IV-2 isoprotein (pI 5.02). Computer analysis of the apoA-IV-2 allele revealed that the single G to T substitution results in the loss of a BbvI and a Fnu4HI restriction enzyme site and in the formation of a new restriction site for the enzyme SfaNI. Protein primary and secondary structure predictions were largely unaffected by this amino acid exchange. These results on the structure of the apoA-IV-1 and apoA-IV-2 alleles suggest that the three other rare isoproteins (apoA-IV-0, apoA-IV-3, and apoA-IV-4) are also due to nucleotide and subsequent amino acid substitutions in the apoA-IV sequence.  相似文献   

12.
Using protein blotting and an immuno-overlay procedure, we have reexamined the cross-reacting material produced by ADH null-activity mutants generated with ethyl methanesulfonate (EMS). Of the 13 mutants, 11 have an immunodetectable polypeptide of wild-type size. The native and urea denatured isoelectric points (pI) establish that 7 of 13 of the mutations have no effect on protein charge. The electrophoretic mobilities of each variant on increasing percent acrylamide gels (Ferguson analysis), reveal that 9 of the 11 immunodetectable mutants have retained the ability to form dimers under native conditions. None of the inactive mutant proteins has the ability to form the "adduct-bound" isozyme. We have found no correlation between protein pI and in vivo stability. The observed frequencies of specific charge class alterations do not dispute the propensity of G:A transitions previously found for EMS mutagenesis.  相似文献   

13.
Accessions from across the range of Tripsacum dectyloides in the US. were assayed electrophoretically for interpopulation variation in seed proteins. Clustering of isoelectric focusing patterns for Tris-HCl and water-soluble proteins revealed high levels of homogeneity. Preliminary resultswith alcohol-soluble proteins, in contrast, showed this fraction to be intrinsically much more variable. Divergent functional roles of the protein fractions themselves could account for this observed difference in variation and are discussed in the paper.  相似文献   

14.
Protamines are small, highly basic DNA-binding proteins found in the sperm of animals. Interestingly, the proportion of arginine residues in one type of protamine, protamine P1, is about 50% in mammals. Upon closer examination, it was found that both the total number of amino acids and the positions of arginine residues have changed considerably during the course of mammalian evolution. This evolutionary pattern suggests that protamine P1 is under an unusual form of purifying selection, in which the high proportion of arginine residues is maintained but the positions may vary. In this case, we would expect that the rate of nonsynonymous substitution is not particularly low compared with that of synonymous substitution, despite purifying selection. We would also expect that the selection for a high arginine content results in a high frequency of the nucleotide G in the coding region of this gene, because all six arginine codons contain at least one G. These expectations were confirmed in our study of mammalian protamine genes. Analysis of nonmammalian vertebrate genes also showed essentially the same patterns of evolutionary changes, suggesting that this unusual form of purifying selection has been active since the origin of bony vertebrates. The protamine gene of an insect species shows similar patterns, although its purifying selection is less intense. These observations suggest that arginine-rich selection is a general feature of protamine evolution. The driving force for arginine-rich selection appears to be the DNA-binding function of protamine P1 and an interaction with a protein kinase in the fertilized egg.  相似文献   

15.
The structural proteins of polyoma virions and capsids were analyzed by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Polyoma virion VP1 was found to be composed of six distinct species which had pI's between pH 6.75 and 5.75. Polyoma capsid VP1 was found to contain four species with pI's between pH 6.60 and 5.75. The different forms of virion and capsid VP1 appeared to be generated by modifications (phosphorylation and acetylation) of the initial translation product. The most basic of the virion VP1 species (pI, pH 6.75) was absent in capsids and was found to be exclusively associated with the viral nucleoprotein complex. Three of the virion VP1 species and three of the capsid VP1 species were found in capsomere preparations enriched for hexon subunits. Two VP1 species were specifically immune precipitated from virions with hemagglutination-inhibiting antibodies. These two VP1 species were common to both virions and capsids. Polyoma virions, but not capsids, possessed a single VP1 species which was immune precipitated with neutralizing antibodies. Both virion and capsid VP2 were found to have pI's of approximately pH 5.50. Virion VP3 had a pI of approximately pH 7.00, whereas capsid VP3 had a pI of approximately pH 6.50.  相似文献   

16.
Wang J  Zhang L  Li J  Lawton-Rauh A  Tian D 《Gene》2011,482(1-2):24-33
Plant resistance genes (R-genes) evolve rapidly in response to changing environments. What are the most remarkable signatures of fast adaptive genes, besides the commonly revealed rapid divergence and high non-synonymous substitution rate? Here we investigated these changes in five R-loci following recent differentiation between Arabidopsis thaliana and Arabidopsis lyrata. Extreme differences in evolutionary rates were observed: e.g., an overall 5.46-9.83-fold different nucleotide diversity at two R-loci between species, ten-fold higher non-synonymous substitution rates within one species versus the other, significantly different Ka/Ks ratios between species for the same R-gene, and high interspecific divergence at one R-locus. Particularly, we observed an elevated level of trans-specific polymorphism at one R-locus and a differentially maintained presence/absence polymorphism at another. The high frequency of ancestral polymorphisms amongst R-genes suggests that the persistence of some functional variation is an important evolutionary mechanism shaping genetic variation in R-genes, while the variation of presence/absence polymorphisms provides a potential mechanism for malleable activation of adaptive resistance response pathways. The distinct patterns among R-genes suggest that the same R-gene ortholog can be quickly shaped by different evolutionary processes, e.g., purifying selection in one species but positive selection in a closely-related species.  相似文献   

17.
Rat liver nuclear ribonucleoprotein particles were prepared by two different methods and defined as 40S ribonucleoprotein (40S RNP) and heterogeneous nuclear ribonucleoprotein (HnRNP) particles. The RNP particles were either solubilized in 8 M urea--6 mM 2-mercaptoethanol--20 mM glycine--20 mM Tris--HCl (pH 8.4) or subjected to removal of RNA by phenol extraction prior to solubilizing the proteins in the urea buffer. The proteins associated with 40S RNP and HnRNP were heterogeneous and very similar in their electrophoretic patterns when analyzed by two-dimensional PAGE, except a protein with molecular weight of 62 000 and an isoelectric point (pI) of 6.2 was present only in HnRNP particles. At least 12 major and 22 minor components could be identified in both preparations. The major proteins were found at pI values varying from 6.0 to 8.5 and with molecular weights from 32 000 to 42 000, and a group of proteins with molecular weight approximately 65 000 were more prominent in HnRNP than in 40S RNP. The other components were found mainly at pI ranges from 5.0 to 6.5 with molecular weights from 43 000 to 65 000. The phenol method extracted essentially all proteins associated with either 40S RNP and HnRNP, but was less effective in extracting a group of proteins with pI values from 5.0 to 5.5 and more efficient for proteins with pI values from 7.5 to 8.5. When chromatin proteins isolated by phenol extraction were compared with HnRNP particle proteins isolated by the same method, the electrophoretic mobilities of the HnRNP particle proteins were found to be identical with a fraction nonhistone chromatin proteins. The 40S RNP particles were further purified by metrizamide isopycnic density gradient centrifugation. The electrophoretic patterns of these proteins were very similar to those prepared by sucrose density gradient centrifugation. Therefore, we concluded that the proteins of RNP particles constituted part of the chromatin proteins.  相似文献   

18.
Polymorphism and evolution of influenza A virus genes   总被引:12,自引:1,他引:11  
The nucleotide sequences of four genes of the influenza A virus (nonstructural protein, matrix protein, and a few subtypes of hemagglutinin and neuraminidase) are compiled for a large number of strains isolated from various locations and years, and the evolutionary relationship of the sequences is investigated. It is shown that all of these genes or subtypes are highly polymorphic and that the polymorphic sequences (alleles) are subject to rapid turnover in the population, their average age being much less than that of higher organisms. Phylogenetic analysis suggests that most polymorphic sequences within a subtype or a gene appeared during the last 80 years and that the divergence among the subtypes of hemagglutinin genes might have occurred during the last 300 years. The high degree of polymorphism in this RNA virus is caused by an extremely high rate of mutation, estimated to be 0.01/nucleotide site/year. Despite the high rate of mutation, most influenza virus genes are apparently subject to purifying selection, and the rate of nucleotide substitution is substantially lower than the mutation rate. There is considerable variation in the substitution rate among different genes, and the rate seems to be lower in nonhuman viral strains than in human strains. The difference might be responsible for the so-called freezing effect in some viral strains.   相似文献   

19.
Summary Protein extracts from four self-incompatible genotypes of Phalaris coerulescens were subjected to analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and ultra-thin isoelectric focusing. A comparison between stigma, root and leaf extracts showed that there was no significant difference in electrophoretic or isoelectric focusing patterns between the genotypes for both root and leaf proteins. However, stigma protein patterns did vary between genotypes especially within the molecular weight region of 43 000–97 000 and within the pI range 5–7. The stigma-specific changes strongly suggest a link between the self-incompatible genotype and these stigma proteins. However, because there are two loci involved, it is not yet possible to precisely assign particular proteins to each S- or Z-allele.  相似文献   

20.
Gamete‐recognition proteins often, but not always, evolve rapidly. We explored how variation in sperm bindin influences reproductive success of the sea urchin Strongylocentrotus purpuratus during group spawning in the sea. Despite large variation in male and female abundance and neighbor distances, males with common genotypes had higher reproductive success than males with rare genotypes. However, males with a relatively uncommon proline‐for‐serine substitution were the most successful. Females also showed a fitness consequence of sperm‐bindin genotype, suggesting linkage disequilibrium between the sperm‐bindin locus and the egg receptor locus. Females with common genotypes had higher reproductive success than rare genotypes, but females with relatively uncommon insertions were most successful. Overall, these results suggest that rare male proteins are selected against, as supported by molecular evidence of purifying selection and probably caused by poor matches to the female receptor protein. Within the pool of moderately common to common alleles, however, individuals with less‐common functional variants were favored and probably maintained by negative frequency‐dependent selection. These results support the hypothesis that sperm availability and sexual conflict influence the evolution of gamete recognition systems in broadcast spawners and highlight the benefits of combining fitness measures with molecular signatures for estimation of patterns of selection.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号