A Biochemical Mechanism for Nonrandom Mutations and Evolution

Wright, Barbara E.

doi:10.1128/jb.182.11.2993-3001.2000

Cited by 80 publications

(68 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the positions of the mutations in base pairing regions were also labeled to indicate the retained structure among the different sequences (Figure 2). There are two possible explanations for this: 1) there may be a requirement for base pairing to retain the structure needed for autocatalysis of the intron, which would give a selection pressure for compensatory changes, and 2) the tendency for a higher mutation rate in unpaired or mispaired bases on structures formed by single-stranded DNA during transcription, for example (Wright, 2000).…”

Section: Discussionmentioning

confidence: 99%

tRNALeu intron (UAA) of Ficus carica L.: genetic diversity and evolutionary patterns

2015

View full text Add to dashboard Cite

ABSTRACT. Cytoplasmic chloroplast DNA was explored to establish genetic relationships among Ficus carica cultivars and elucidate the molecular evolution of the species. The results suggest the occurrence of haplotype and nucleotide diversity. Conserved group I intron sequence motifs were detected and showed a common secondary structure, despite the presence of some mutations on their sequences. The neighbor-joining dendrogram showed a continuous diversity that characterizes local resources. The maximum parsimony tree, with an RI index of 0.507, indicated minimal homoplasy within the data set. Furthermore, our results demonstrate that the trnL intron is the seat of numerous substitutions. Herein, new insight on the mechanism involved in the evolution of the trnL intron in the fig is presented. From the study, it appears that there is an explicit rejection of the null hypothesis in F. carica. A scenario of positive selection and recent expansion of F. carica genotypes across Tunisia seems to be retained.

show abstract

Section: Discussionmentioning

confidence: 99%

tRNALeu intron (UAA) of Ficus carica L.: genetic diversity and evolutionary patterns

2015

View full text Add to dashboard Cite

show abstract

“…Transcription can lead to mutation by driving localized supercoiling and the accumulation of DNA secondary structures containing unpaired and/or mispaired bases known to be vulnerable to mutations (reviewed by Wright, 2000). Using a new computer algorithm, it has been possible to predict mutation frequencies in derepressed genes of Escherichia coli auxotrophs and in the human p53 cancer gene (Wright et al, 2002(Wright et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

Increased transcription rates correlate with increased reversion rates in leuB and argH Escherichia coli auxotrophs

et al. 2004

Self Cite

View full text Add to dashboard Cite

Escherichia coli auxotrophs of leuB and argH were examined to determine if higher rates of transcription in derepressed genes were correlated with increased reversion rates. Rates of leuB and argH mRNA synthesis were determined using half-lives and concentrations, during exponential growth and at several time points during 30 min of amino acid starvation. Changes in mRNA concentration were primarily due to increased mRNA synthesis and not to increased stability. Four strains of E. coli amino acid auxotrophs, isogenic except for relA and argR, were examined. In both the leuB and argH genes, rates of transcription and mutation were compared. In general, strains able to activate transcription with guanosine tetraphosphate (ppGpp) had higher rates of mRNA synthesis and mutation than those lacking ppGpp (relA2 mutants). argR knockout strains were constructed in relA + and relA mutant strains, and rates of both argH reversion and mRNA synthesis were significantly higher in the argR knockouts than in the regulated strains. A statistically significant linear correlation between increased rates of transcription and mutation was found for data from both genes. In general, changes in mRNA half-lives were less than threefold, whereas changes in rates of mRNA synthesis were often two orders of magnitude. The results suggest that specific starvation conditions target the biosynthetic genes for derepression and increased rates of transcription and mutation.

show abstract

“…Evidence for mutagenesis in SSs and was pioneered by Ripley and Glickman (1983), and more recently recognized as the result of transcription-driven supercoiling that stabilizes SSs containing intrinsically mutable unpaired bases (Reimers et al, 2004;Schmidt et al, 2006;Wright, 2000;Wright et al, 2002;Wright et al, 2003;Wright, 2004;Wright et al, 2004;Wright et al, 2006). Hoede et al (2006) investigated the influence of transcription-directed mutagenesis (TDM) on genome evolution, and demonstrated that the control of TDM through DNA SSs is under selection in the E. coli bacterial genome.…”

Section: Transcription-driven Mutagenesis and S-ibmentioning

confidence: 99%

I. VH gene transcription creates stabilized secondary structures for coordinated mutagenesis during somatic hypermutation

Wright

Schmidt

Minnick

et al. 2008

Molecular Immunology

Self Cite

View full text Add to dashboard Cite

During the adaptive immune response, antigen challenge triggers a million-fold increase in mutation rates in the variable region antibody genes. The frequency of mutation is causally and directly linked to transcription, which provides ssDNA and drives supercoiling that stabilizes secondary structures containing unpaired, intrinsically mutable bases. Simulation analysis of transcription in VH5 reveals a dominant 65 nt secondary structure in the non-transcribed strand containing six sites of mutable ssDNA that have also been identified independently in human B cell lines and in primary mouse B cells. This dominant structure inter-converts briefly with less stable structures and is formed repeatedly during transcription, due to periodic pauses and backtracking. In effect, this creates a stable yet dynamic "mutability platform" consisting of ever-changing patterns of unpaired bases that are simultaneously exposed and therefore able to coordinate mutagenesis. Such a complex of secondary structures may be the source of ssDNA for enzyme-based diversification, which ultimately results in high affinity antibodies.

show abstract

A Biochemical Mechanism for Nonrandom Mutations and Evolution

Cited by 80 publications

References 105 publications

tRNALeu intron (UAA) of Ficus carica L.: genetic diversity and evolutionary patterns

tRNALeu intron (UAA) of Ficus carica L.: genetic diversity and evolutionary patterns

Increased transcription rates correlate with increased reversion rates in leuB and argH Escherichia coli auxotrophs

I. VH gene transcription creates stabilized secondary structures for coordinated mutagenesis during somatic hypermutation

Contact Info

Product

Resources

About