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61.
Noboru Sueoka 《Journal of molecular evolution》1993,37(2):137-153
Using a general form of the directional mutation theory, this paper analyzes the effect of mutations in mutator genes on the
G + C content of DNA, the frequency of substitution mutations, and evolutionary changes (cumulative mutations) under various
degrees of selective constraints. Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide
pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will
be much lower than the frequency immediately after the mutator mutation takes place. This prediction explains the wide variation
of the DNA G + C content among unicellular organisms and possibly also the wide intragenomic heterogeneity of third codon
positions for the genes of multicellular eukaryotes. The present analyses lead to several predictions that are not consistent
with a number of the frequently held assumptions in the field of molecular evolution, including belief in a constant rate
of evolution, symmetric branching of phylogenetic trees, the generality of higher mutation frequency for neutral sets of nucleotides,
the notion that mutator mutations are generally deleterious because of their high mutation rates, and teleological explanations
of DNA base composition.
Presented at the NATO Advanced Research Workshop onGenome Organization and Evolution, Spetsai, Greece, 16–22 September 1992 相似文献
62.
Geun-Shik Lee Yuanzheng He Edward J. Dougherty Maria Jimenez-Movilla Matteo Avella Sean Grullon David S. Sharlin Chunhua Guo John A. Blackford Jr. Smita Awasthi Zhenhuan Zhang Stephen P. Armstrong Edra C. London Weiping Chen Jurrien Dean S. Stoney Simons Jr. 《The Journal of biological chemistry》2013,288(21):15167-15180
TTLL5/STAMP (tubulin tyrosine ligase-like family member 5) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamptm/tm) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamptm/tm sperm tails in conjunction with substantial reduction in α-tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of WT versus Stamptm/tm males despite the levels of WT STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for α-tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility. 相似文献
63.
The persistence of life requires populations to adapt at a rate commensurate with the dynamics of their environment. Successful populations that inhabit highly variable environments have evolved mechanisms to increase the likelihood of successful adaptation. We introduce a 64 × 64 matrix to quantify base-specific mutation potential, analyzing four different replicative systems, error-prone PCR, mouse antibodies, a nematode, and Drosophila. Mutational tendencies are correlated with the structural evolution of proteins. In systems under strong selective pressure, mutational biases are shown to favor the adaptive search of space, either by base mutation or by recombination. Such adaptability is discussed within the context of the genetic code at the levels of replication and codon usage.Supplementary material to this paper is available in electronic form.Reviewing Editor: Dr. Edward Trifonov 相似文献
64.
目的建立心脏特异表达LMNAE82K转基因小鼠,为研究LMNAE82K与心肌病发病机制的关系提供工具动物。方法把LMNAE82K基因插入α-MHC启动子下游,构建转基因表达载体,显微注射法建立C57BL/6JLMNAE82K转基因小鼠,PCR鉴定转基因小鼠的基因型,采用Western Blot鉴定LMNAE82K在心脏组织中的表达,H&E染色和超声检测转基因小鼠心脏的病理改变。结果建立了2个心脏组织特异表达LMNAE82K的转基因小鼠品系。超声检查显示转基因小鼠心室壁变薄,收缩期容积和舒张期容积增加,射血分数及短轴缩短率降低。结论LMNAE82K转基因小鼠具有LMNAE82K引起的家族性扩心病有类似的病理变化,为研究LMNAE82K与心肌病发病机制的关系的研究提供了有价值的疾病动物模型。 相似文献
65.
Summary Based on a dose-survival curve, a radiation dose of 3.99 C/kg was used to induce antibiotic-resistant mutants inBacteroides fragilis. Escherichia coli B/r membrane fragments were employed as a reducing agent. Antibiotic-resistant mutants ofB. fragilis were utilized to study the mechanism by which these organisms become resistant to selected chemotherapeutic agents. Decreased accumulation of tetracycline by resistant mutants ofB. fragilis suggests that the resistance to this antibiotic is associated with the outer membrane permeability. There is a marked difference in the inhibitory action of rifampicin on RNA polymerase activity in rifampicin-sensitive and-resistant strains ofB. fragilis. This enzyme is, therefore, the likely target for inhibition of bacterial growth in this anaerobe by rifampicin. 相似文献
66.
Wentai Ma Jing Yang Haoyi Fu Chao Su Caixia Yu Qihui Wang Ana Tereza Ribeiro de Vasconcelos Georgii A.Bazykin Yiming Bao Mingkun Li 《基因组蛋白质组与生物信息学报(英文版)》2022,20(1):60-69
A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequencing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the sam... 相似文献
67.
Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications 总被引:29,自引:0,他引:29
Summary We have obtained a revised estimate of the pattern of point mutation by considering more pseudogene sequences. Compared with our previous estimate, it agrees better with expectations based on the double-strand structure of DNA. The revised pattern, like the previous one, indicates that mutation occurs nonrandomly among the four nucleotides. In particular, the proportion of transitional mutations (59%) is almost twice as high as the value (33%) expected under random mutation. The same high proportion of transitions is observed in synonymous substitutions in genes. The proportion of transitional changes observed among electrophoretic variants of human hemoglobin is about the same as that predicted by the revised pattern of mutation. We also show that nonrandom mutation increases, by about 15%, the proportion of synonymous mutations due to single-nucleotide changes in the codon table, and increases, from 10% to 50%, the rate of synonymous mutation in the seven genes studied. However, nonrandom mutation reduces (by about 10%) the proportion of polar changes among nonsynonymous mutations in a gene. As far as single-nucleotide changes (in the codon table) are concerned, nonrandom mutation only slightly favors relatively conservative amino acid interchanges, and has virtually no effect on the proportions of radical changes and nonsense mutations. 相似文献
68.
Ruth Jaén‐Molina Águedo Marrero‐Rodríguez J. Alfredo Reyes‐Betancort Arnoldo Santos‐Guerra José Naranjo‐Suárez Juli Caujapé‐Castells 《Molecular ecology resources》2015,15(1):42-56
We use a comprehensive subset of Canarian angiosperms corresponding to 23 families, 35 genera and 60 Canarian endemic taxa to test whether this flora is suitable to taxonomic identification with the two proposed plant DNA barcode sequences and whether these sequences may reveal the existence of cryptic species overlooked by morphology. The rate of discrimination success between the insular congeneric samples using the rbcL+matK combination and a ‘character‐based’ approach (where we use only the combination of nucleotide positions in an alignment that allows unambiguous species identification) is higher (82.29%) than that obtained with the ‘distance‐based’ approach (80.20%) used by the CBOL Plant Working Group in 2009 and also when compared with tests conducted in other floras. This suggests that the molecular identification of the Canarian endemic flora can be achieved as successfully as in other floras where the incidence of radiation is not as relevant. The facts that (i) a distance‐based criterion was unable to discriminate between congeneric and conspecific comparisons and (ii) only the character‐based discrimination criterion resolved cases that the distance‐based criterion did not, further support the use of a character discrimination approach for a more efficient DNA barcoding of floras from oceanic islands like the Canaries. Thus, a barcoding gap seems not to be necessary for the correct molecular characterization of the Canarian flora. DNA barcodes also suggest the possible existence of cryptic taxa to be further investigated by morphology and that the current taxonomic status of some of the taxa analysed may need revision. 相似文献
69.
Role of Smad4 (DPC4) inactivation in human cancer 总被引:23,自引:0,他引:23
The tumor suppressor gene Smad4 (DPC4) at chromosome 18q21.1 belongs to the Smad family, which mediates the TGFbeta signaling pathway suppressing epithelial cell growth. This review summarizes the mutational events of the Smad4 gene in human cancer. The Smad4 gene is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancer. In this syndrome, polyps are formed by inactivation of the Smad4 gene through germline mutation and loss of the unaffected wild-type allele. In pancreatic and colorectal cancer, inactivation of the Smad4 gene through homozygous deletion or intragenic mutation occurs frequently in association with malignant progression. However, mutation of this gene is seen only occasionally in the rest of human cancers. The majority of Smad4 gene mutations in human cancer are missense, nonsense, and frameshift mutations at the mad homology 2 region (MH2), which interfere with the homo-oligomer formation of Smad4 protein and the hetero-oligomer formation between Smad4 and Smad2 proteins, resulting in disruption of TGFbeta signaling. Supporting evidence for the above observation was provided by genetically manipulated mice carrying either a heterozygote of the Smad4 gene or a compound heterozygote of the Smad4 and APC genes, which develop either gastrointestinal polyps/cancer mimicking familial juvenile polyposis or progressed colorectal cancer, respectively. 相似文献
70.
Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs) and sequence analysis of noncoding regions of chloroplast DNA were used to investigate 37 populations of Eritrichium nanum covering its total distribution area, the European Alps. There was no haplotypic variation within the populations, and most haplotypes were restricted to single sites or to neighbouring populations, suggesting low levels of long distance gene flow via seeds. The present geographical distribution of haplotypes probably reflects an ancient geographical pattern within two regions in the intensely glaciated western and eastern central Alps identified as genetic hotspot areas. These two regions contained seven of the total of 11 haplotypes, including many of the most derived ones. The divergent haplotypes formed closely related groups, which supported a separate evolution of these haplotypes in these two regions and, more importantly, gave strong evidence for the in situ survival of these populations on nunataks within the western and eastern central Alps during Pleistocene glaciation. This result is in concordance with a previous study on E. nanum using nuclear markers. Only one haplotype was common and widespread throughout the distributional range of E. nanum. At the same time, it was the evolutionarily basal-most and all other haplotypes were best described as its descendants. This haplotype is hypothesized to be genetically identical to a Tertiary Alpine colonizing ancestor, whose distribution was secondarily fragmented and infiltrated by derived haplotypes originating through local mutations. 相似文献