SPONTANEOUS MUTATION IN IMMUNOGLOBULIN GENES

Abstract RAD3 functions in DNA repair and transcription in Saccharomyces cerevisiae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the potential involvement of the Rad3 protein in mismatch correction by comparing heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutation rate but did not prevent heteroduplex repair or bias its directionality. Instead, the efficiency of mismatch correction was enhanced in the rad3-1 strain. This surprising result prompted us to examine expression of yeast mismatch repair genes. We determined that MSH2, but not MLH1, is transcriptionally regulated during the cell-cycle like PMSl, and that rad3-1 does not increase the transcript levels for these genes in log phase cells. These observations suggest that the rad3-1 mutation gives rise to an enhanced efficiency of mismatch correction via a process that does not involve transcriptional regulation of mismatch repair. Interestingly, mismatch repair also was more efficient when error-editing by yeast DNA polymerase δ was eliminated. We discuss our results in relation to possible mechanisms that may link the rad3-1 mutation to mismatch correction efficiency.

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Inherited Differences in Crossing Over and Gene Conversion Frequencies Between Wild Strains of Sordaria fimicola From “Evolution Canyon”

Genetics ◽

10.1093/genetics/159.4.1573 ◽

2001 ◽

Vol 159 (4) ◽

pp. 1573-1593

Author(s):

Muhammad Saleem ◽

Bernard C Lamb ◽

Eviatar Nevo

Keyword(s):

Genetic Variation ◽

Gene Conversion ◽

Spontaneous Mutation ◽

Crossing Over ◽

Natural Genetic Variation ◽

Evolution Canyon ◽

Wild Strains ◽

Sordaria Fimicola ◽

First And Second Generation ◽

Consistent Direction

Abstract Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in “Evolution Canyon,” Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II.

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Imbalanced deoxyribonucleoside triphosphate pools and spontaneous mutation rates determined during dCMP deaminase-defective bacteriophage T4 infections.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)45607-4 ◽

1987 ◽

Vol 262 (12) ◽

pp. 5546-5553 ◽

Cited By ~ 2

Author(s):

R.G. Sargent ◽

C.K. Mathews

Keyword(s):

Bacteriophage T4 ◽

Spontaneous Mutation ◽

Mutation Rates ◽

Deoxyribonucleoside Triphosphate

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Spontaneous Mutational Effects on Reproductive Traits of Arabidopsis thaliana

Genetics ◽

10.1093/genetics/155.1.369 ◽

2000 ◽

Vol 155 (1) ◽

pp. 369-378 ◽

Cited By ~ 5

Author(s):

Ruth G Shaw ◽

Diane L Byers ◽

Elizabeth Darmo

Keyword(s):

Arabidopsis Thaliana ◽

Spontaneous Mutation ◽

Reproductive Traits ◽

Dry Mass ◽

Negative Effects ◽

Single Seed Descent ◽

Standardized Measures ◽

Significant Divergence ◽

Further Development ◽

Mutational Variance

Abstract A study of spontaneous mutation in Arabidopsis thaliana was initiated from a single inbred Columbia founder; 120 lines were established and advanced 17 generations by single-seed descent. Here, we report an assay of reproductive traits in a random set of 40 lines from generations 8 and 17, grown together at the same time with plants representing generation 0. For three reproductive traits, mean number of seeds per fruit, number of fruits, and dry mass of the infructescence, the means did not differ significantly among generations. Nevertheless, by generation 17, significant divergence among lines was detected for each trait, indicating accumulation of mutations in some lines. Standardized measures of mutational variance accord with those obtained for other organisms. These findings suggest that the distribution of mutational effects for these traits is approximately symmetric, in contrast to the usual assumption that mutations have predominantly negative effects on traits directly related to fitness. Because distinct generations were grown contemporaneously, each line was represented by three sublines, and seeds were equal in age, these estimates are free of potentially substantial sources of bias. The finding of an approximately symmetric distribution of mutational effects invalidates the standard approach for inferring properties of spontaneous mutation and necessitates further development of more general approaches that avoid restrictions on the distribution of mutational effects.

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Antagonism of Ultraviolet-Light Mutagenesis by the Methyl-Directed Mismatch-Repair System of Escherichia coli

Genetics ◽

10.1093/genetics/154.2.503 ◽

2000 ◽

Vol 154 (2) ◽

pp. 503-512 ◽

Cited By ~ 1

Author(s):

Hongbo Liu ◽

Stephen R Hewitt ◽

John B Hays

Keyword(s):

Escherichia Coli ◽

Mismatch Repair ◽

Excision Repair ◽

Spontaneous Mutation ◽

Repair System ◽

Uv Mutagenesis ◽

Repair Protein ◽

Mismatch Repair System

Abstract Previous studies have demonstrated that the Escherichia coli MutHLS mismatch-repair system can process UV-irradiated DNA in vivo and that the human MSH2·MSH6 mismatch-repair protein binds more strongly in vitro to photoproduct/base mismatches than to “matched” photoproducts in DNA. We tested the hypothesis that mismatch repair directed against incorrect bases opposite photoproducts might reduce UV mutagenesis, using two alleles at E. coli lacZ codon 461, which revert, respectively, via CCC → CTC and CTT → CTC transitions. F′ lacZ targets were mated from mut+ donors into mutH, mutL, or mutS recipients, once cells were at substantial densities, to minimize spontaneous mutation prior to irradiation. In umu+ mut+ recipients, a range of UV fluences induced lac+ revertant frequencies of 4–25 × 10−8; these frequencies were consistently 2-fold higher in mutH, mutL, or mutS recipients. Since this effect on mutation frequency was unaltered by an Mfd− defect, it appears not to involve transcription-coupled excision repair. In mut+ umuC122::Tn5 bacteria, UV mutagenesis (at 60 J/m2) was very low, but mutH or mutL or mutS mutations increased reversion of both lacZ alleles roughly 25-fold, to 5–10 × 10−8. Thus, at UV doses too low to induce SOS functions, such as Umu2′D, most incorrect bases opposite occasional photoproducts may be removed by mismatch repair, whereas in heavily irradiated (SOS-induced) cells, mismatch repair may only correct some photoproduct/base mismatches, so UV mutagenesis remains substantial.

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Whole-Genome Effects of Ethyl Methanesulfonate-Induced Mutation on Nine Quantitative Traits in Outbred Drosophila melanogaster

Genetics ◽

10.1093/genetics/157.3.1257 ◽

2001 ◽

Vol 157 (3) ◽

pp. 1257-1265 ◽

Cited By ~ 3

Author(s):

Hsiao-Pei Yang ◽

Ana Y Tanikawa ◽

Wayne A Van Voorhies ◽

Joana C Silva ◽

Alexey S Kondrashov

Keyword(s):

Drosophila Melanogaster ◽

Quantitative Traits ◽

Spontaneous Mutation ◽

Developmental Time ◽

Ethyl Methanesulfonate ◽

Induced Mutations ◽

Mean Values ◽

Eye Color ◽

Recessive Mutations ◽

The Mean

Abstract We induced mutations in Drosophila melanogaster males by treating them with 21.2 mm ethyl methanesulfonate (EMS). Nine quantitative traits (developmental time, viability, fecundity, longevity, metabolic rate, motility, body weight, and abdominal and sternopleural bristle numbers) were measured in outbred heterozygous F3 (viability) or F2 (all other traits) offspring from the treated males. The mean values of the first four traits, which are all directly related to the life history, were substantially affected by EMS mutagenesis: the developmental time increased while viability, fecundity, and longevity declined. In contrast, the mean values of the other five traits were not significantly affected. Rates of recessive X-linked lethals and of recessive mutations at several loci affecting eye color imply that our EMS treatment was equivalent to ∼100 generations of spontaneous mutation. If so, our data imply that one generation of spontaneous mutation increases the developmental time by 0.09% at 20° and by 0.04% at 25°, and reduces viability under harsh conditions, fecundity, and longevity by 1.35, 0.21, and 0.08%, respectively. Comparison of flies with none, one, and two grandfathers (or greatgrandfathers, in the case of viability) treated with EMS did not reveal any significant epistasis among the induced mutations.

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