Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications

Li, Wen-Hsiung; Wu, Chung‐I; Luo, Chi‐Cheng

doi:10.1007/bf02100628

Cited by 340 publications

(233 citation statements)

References 56 publications

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“…It is clear that the transitional changes predominate at all colon positions, particularly at the third position. This tendency has also been observed for pseudogenes of DNA organisms (Gojobori et al 1982;Li et al 1984). Among the four different types of transitional changes, the G-~A change is most frequent at all positions.…”

supporting

confidence: 59%

Patterns of nucleotide substitutions in influenza A virus genes

Saitou

1987

The Japanese journal of genetics

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.The pattern of nucleotide substitution among the four nucleotides (A, T, C, and G) was studied for seven different genes of the influenza A virus. The direction of substitution was inferred by examining phylogenetic trees reconstructed (Saitou and Nei 1986), and the relative frequency of nucleotide substitutions was computed by Gojobori et at. 's (1982) method. It is found that the transitional changes (between A and G and between T and C) are much more abundant (about 70%) than expected under random substitution. Among the four types of transitional changes, the G-±A change is most frequent. There are negative correlations between the chemical distance of nucleotides and the substitution pattern at the first and second colon positions for all genes examined. This result suggests that the influenza virus genes are subject to the purifying selection even though they show an extraordinary high substitution rate.

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supporting

confidence: 59%

Patterns of nucleotide substitutions in influenza A virus genes

Saitou

1987

The Japanese journal of genetics

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“…The number of A/G substitutions was close to that of C/T substitutions, and the number of A/C substitutions was close to that of G/T substitutions, reflecting complementary strand symmetry. A/T substitutions were the least frequent among the six types, a pattern observed in pseudogenes or noncoding regions and indicating a lower mutation rate (Li et al 1984;Zhao et al 2000). Transitions accounted for 65.6% of the total substitutions in this genome-wide collection of SNP data.…”

Section: Substitution Patterns and Frequency Biasmentioning

confidence: 75%

“…Single nucleotide polymorphism (SNP) data and information about surrounding sequence motifs are suitable for studying mutational processes in human and other genomes (Zavolan and Kepler 2001). However, in humans previous analyses of SNP variation and neighboringnucleotide effects have largely been limited to pseudogenes or a limited number of genes with known effects, many of which are disease-causing (e.g., Gojobori et al 1982;Li et al 1984;Cooper and Krawczak 1990;Krawczak et al 1998). In plants, effects of neighboring nucleotides have been extensively studied in chloroplasts (e.g., Morton 1995;Morton et al 1997).…”

mentioning

confidence: 99%

Neighboring-Nucleotide Effects on Single Nucleotide Polymorphisms: A Study of 2.6 Million Polymorphisms Across the Human Genome

2002

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We investigated substitution patterns and neighboring-nucleotide effects for 2,576,903 single nucleotide polymorphisms (SNPs) publicly available through the National Center for Biotechnology Information (NCBI). The proportions of substitutions were A/G, 32.77%; C/T, 32.81%; A/C, 8.98%; G/T, 9.06%; A/T, 7.46%; and C/G, 8.92%. The two nucleotides immediately neighboring the variable site showed major deviation from genome-wide and chromosome-specific expectations, although lesser biases extended as far as 200 bp. On the 5′ side, the biases for A, C, G, and T were 1.43%, 4.91%, −1.70%, and −4.62%, respectively. These biases were −4.44%, −1.59%, 5.05%, and 0.99%, respectively, on the 3′ side. The neighboring-nucleotide patterns for transitions were dominated by the hypermutability effects of CpG dinucleotides. Transitions were more common than transversions, and the probability of a transversion increased with increasing A + T content at the two adjacent sites. Neighboring-nucleotide biases were not consistent among chromosomes, with Chromosomes 19 and 22 standing out as different from the others. These data provide genome-wide information about the effects of neighboring nucleotides on mutational and evolutionary processes giving rise to contemporary patterns of nucleotide occurrence surrounding SNPs

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“…One physicochemical process, spontaneous deamination of methylated cytosines to thymines, is the likely cause of mutations that occur at a CpG dinucleotide, approximately one quarter of all factor IX mutations [Gojobori et al, 1982]. Certain mutagens, however, may preferentially affect CpG residues [Li et al, 1984].…”

Section: The Human Factor IX Gene As a Germline "Mutagen Test"mentioning

confidence: 99%

p53 As a mutagen test in breast cancer

Hill

Sommer

2002

Environ and Mol Mutagen

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The p53 gene is mutated in about half of all tumors. The p53 gene can be used as a “mutagen test,” that is, the relative frequencies of the different types of mutation can be used as an epidemiological tool to explore the contribution of exogenous mutagens vs. endogenous processes in particular cancers. p53 has been used as a mutagen test in breast cancer. Surprisingly, the pattern of p53 mutations differs among 15 geographically and ethnically diverse populations. In contrast, mutation patterns in the human factor IX gene are similar in geographically and ethnically diverse populations. Diverse p53 mutation patterns in breast cancer are consistent with a significant contribution by a diversity of exogenous mutagens. Breast tissue may be uniquely sensitive to lipophilic mutagens because of its unique architecture, characterized by tiny islands of cancer‐prone mammary epithelial cells surrounded by a sea of adipocytes. Mammary epithelial cells may be differentially susceptible to released lipophilic mutagens preferentially concentrated in adjacent adipocytes and originating in the diet. To test this hypothesis, we developed a method for measuring mutation load from ethanol‐fixed, paraffin‐embedded human tissues immunohistochemically stained with anti‐p53 antibodies. Single cells staining positively for p53 overabundance are microdissected and the gene is sequenced. It is possible to identify individuals with a high mutation load in normal breast tissue and who are presumably at increased risk for breast cancer. In addition, analysis of the p53 gene with appropriate mutation detection methodology markedly improves the prediction of early recurrence, treatment failure, and death in breast cancer patients. Mutagen tests and mutation load measurements are useful tools to identify the role of mutagens in breast cancer. Environ. Mol. Mutagen. 39:216–227, 2002. © 2002 Wiley‐Liss, Inc.

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Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications

Cited by 340 publications

References 56 publications

Patterns of nucleotide substitutions in influenza A virus genes

Patterns of nucleotide substitutions in influenza A virus genes

Neighboring-Nucleotide Effects on Single Nucleotide Polymorphisms: A Study of 2.6 Million Polymorphisms Across the Human Genome

p53 As a mutagen test in breast cancer

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