Showing papers on "Mutation (genetic algorithm) published in 1981"

DNA Polymorphism Detectable by Restriction Endonucleases

Abstract: Data on DNA polymorphisms detected by restriction endonucleases are rapidly accumulating. With the aim of analyzing these data, several different measures of nucleon (DNA segment) diversity within and between populations are proposed, and statistical methods for estimating these quantities are developed. These statistical methods are applicable to both nuclear and nonnuclear DNAs. When evolutionary change of nucleons occurs mainly by mutation and genetic drift, all the measures can be expressed in terms of the product of mutation rate per nucleon and effective population size. A method for estimating nucleotide diversity from nucleon diversity is also presented under certain assumptions. It is shown that DNA divergence between two populations can be studied either by the average number of restriction site differences or by the average number of nucleotide differences. In either case, a large number of different restriction enzymes should be used for studying phylogenetic relationships among related organisms, since the effect of stochastic factors on these quantities is very large. The statistical methods developed have been applied to data of Shah and Langley on mitochondrial (mt)DNA from Drosophila melanogaster, simulans and virilis. This application has suggested that the evolutionary change of mtDNA in higher animals occurs mainly by nucleotide substitution rather than by deletion and insertion. The evolutionary distances among the three species have also been estimated.

Estimating levels of gene flow in natural populations

Abstract: The results from a simulation model of selection, mutation and genetic drift in a geographically subdivided population are presented. The infinite-alleles mutation model of Kimura and Crow (1964) is asumed, and both advantageous and deleterious mutations are considered. It is shown that the average frequency of an allele conditioned on the number of local populations it appears in—the conditional average frequency—is approximately independent of both the selection intensity and mutation rates assumed, but depends strongly on the overall level of gene flow. This result justifies the use of the conditional average frequency to obtain a rough estimate of the level of gene flow in a subdivided population. Data from 16 species are presented and discussed. There are large differences in the conditional average frequencies of different species, although there is some consistency within taxa. Some species apparently have high levels of gene flow and others, particularly salamanders, have low levels. Alternative explanations for the patterns found in the data are considered.

Elevated spontaneous mutation rate in Bloom syndrome fibroblasts

Abstract: The rates of spontaneous mutation to 6-thioguanine resistance were determined in fibroblasts derived from normal and two Bloom syndrome individuals (GM 2548 and GM 1492). Two methods were utilized to determine the rates. Method I obtained the spontaneous mutation rate from the increase in the mutation frequency of a cell population in logarithmic-phase growth over 10 days. The two Bloom syndrome strains had spontaneous mutation rates of 16 X 10(-6) and 17 X 10(-6) mutations per cell per generation, whereas two normal strains had rates of 1.5 X 10(-6) and 1.1 X 10(-6). Method II utilized fluctuation analysis to measure the rate of spontaneous mutation. This method resulted in rates of 19 X 10(-6) and 23 X 10(-6) mutations per cell per generation in Bloom syndrome cells, compared to rates of 4.6 X 10(-6) and 4.9 X 10(-6) in the control strains. These data suggest that Bloom syndrome may be a mutator mutation, a previously unrecognized phenomenon in humans, and that an elevated spontaneous mutation rate in vivo may be responsible for the clinical phenotype of primordial dwarfism and increased cancer incidence.

Mutation rates of structural chromosome rearrangements in man.

Abstract: The gametic mutation rates of human structural chromosome rearrangements have been estimated from rearrangements ascertained from systematic surveys of live births and spontaneous abortions. The mutation rates for rearrangements that survive long enough to give rise to clinically recognized pregnancies are 2.20 X 10(-4) for balanced rearrangements, 3.54 X 10(-4) for unbalanced Robertsonian translocations, and 3.42 X 10(-4) for unbalanced non-Robertsonian rearrangements. These estimates give a mutation rate for all detectable structural chromosome rearrangements of approximately 1 X 10(-3). The most common single rearrangement, the Robertsonian translocation involving chromosomes 13 and 14, has a mutation rate of 1.5 X 10(-4).

Genetic variability maintained by mutation and overdominant selection in finite populations.

Abstract: Mathematical properties of the overdominance model with mutation and random genetic drift are studied by using the method of stochastic differential equations (Ito and McKean 1974). It is shown that overdominant selection is very powerful in increasing the mean heterozygosity as compared with neutral mutations, and if 2 Ns ( N = effective population size; s = selective disadvantage for homozygotes) is larger than 10, a very low mutation rate is sufficient to explain the observed level of allozyme polymorphism. The distribution of heterozygosity for overdominant genes is considerably different from that of neutral mutations, and if the ratio of selection coefficient ( s ) to mutation rate (ν) is large and the mean heterozygosity ( h ) is lower than 0.2, single-locus heterozygosity is either approximately 0 or 0.5. If h increases further, however, heterozygosity shows a multiple-peak distribution. Reflecting this type of distribution, the relationship between the mean and variance of heterozygosity is considerably different from that for neutral genes. When s/v is large, the proportion of polymorphic loci increases approximately linearly with mean heterozygosity. The distribution of allele frequencies is also drastically different from that of neutral genes, and generally shows a peak at the intermediate gene frequency. Implications of these results on the maintenance of allozyme polymorphism are discussed.

Stable Polymorphisms in a Selection Model with Mutation

Abstract: In the continuous-time selection model for a single locus with several alleles, a stable polymorphism persists under mutation. Global stability can be shown for two and three alleles.For the discrete-time case there follows existence and uniqueness of a polymorphism.

Mutation modification in a random environment.

Abstract: It has been widely accepted for some time that natural selection probably adjusts mutation rates toward an intermediate level. Very high mutation rates will cause an overbearing mutational load, while very low rates will not provide adequate genetic variation to allow a population to adapt to a changing environment. It may be that the optimal rate cannot be achieved because of molecular constraints, but the concept of an intermediate optimal rate nonetheless seems a plausible one. Early quantitative work on the evolution of mutation rates attempted to find rates that maximized some measure of population fitness under various models of selection. Kimura (1960, 1967) developed a model in which the deleterious effects of a particular mutation rate were given by the mutation load, L m , an increasing function of the mutation rate,' and the substitution load, Le , a decreasing function of the mutation rate. He found a rate that minimized the combined expression L m + L; and identified this as the optimal .mutation rate. The substitution load in Kimura's model is Haldane's (1957) measure of the deleterious effects of the lag between a change in the environment and the population's evolution to adapt to the change. There does not appear to be universal agreement on the biological significance of this measure (see Ewens, 1979, section 9.2). Levins (1967) presented a model that explicitly incorporated a changing environment thus circumventing the ambiguities connected with Haldane's measure. He was able to numerically calculate mutation rates which maximized the mean fitness of the population. As expected, these optimal rates were of intermediate value. Recent work on the evolution of mutation rates has used modifier theory rather Revised August 25, 1980

In vitro adventitious bud techniques for vegetative propagation and mutation breeding of potato (Solanum tuberosum L.). II. Significance for mutation breeding

Abstract: It was investigated what potentialities for mutation breeding of potato are offered by using adventitious sprouts that arise in vitro from leaf explants (rachis, petiole, leaflet-disc) after X-irradiation. Mutation frequency and chimerism were studied in subterranean and aerial parts in three vegetative generations (vM1, vM2, vM3). Plants obtained from irradiated series produced a very high mutation frequency, a wide mutation spectrum and a very low rate of chimerism. Mutations were observed also in control series, especially in plants derived from the rachis and petiole explant group.

The mutation component of genetic damage.

Abstract: The mutation component, M, is a measure of the proportion of the impact of a genetic condition that is attributable to recurrent mutation. For a trait maintained by balance between mutation and directional selection, M is approximately the broad-sense heritability; for a measured character where the mean and optimum coincide, M is about half the heritability. If the narrow-sense heritability is high, the impact changes relatively rapidly with a change in mutation rate. If the narrow-sense heritability is low, M cannot be predicted, but the change in impact following a change in mutation rate, if any, is very slow.

Tests of 4 controlling-element systems of maize for mutator activity and their interaction with Mu mutator

Abstract: The maize mutator system, Mu, behaves in a non-Mendelian manner that may be expected if it were an extremely active controlling-element system To test this hypothesis, the maize controlling-element systems, adtDt, DsAc ( MP), IEn, and rcuFcu were tested for mutation activity DsAc and rcuFcu tests were the only ones in which new mutants were induced, but at a frequency much lower than that found in Mu crosses The mutation frequency in these controlling-element systems does not differ statistically from that found in control (Non-Mu) populations Tests also were made to determine if Mu will substitute for the regulatory element of any of the 4 conotrolling-element All tests were negative, suggesting that, if Mu is a controlling-element system, it is a different one from those previously described

Genetic Variability and Rate of Gene Substitution in a Finite Population under Mutation and Fluctuating Selection.

Abstract: By using a numerical method of solving stochastic difference equations, the level of genetic variability maintained in a finite population and the rate of gene substitution under several models of fluctuating selection intensities were studied. It is shown that mutation and random genetic drift both play an important role in determining genetic variability and the rate of gene substitution. Compared with the case of neutral mutations, the fluctuation of selection intensity caused by temporal and spatial heterogeneity of environments generally increases the rate of gene substitution, but the level of genetic variability may be increased or decreased, depending upon the model and the parameters used. Although such a type of selection per se can not be ruled out, when mutation is taken into account, it is difficult to explain both the observed amount of genetic variability and the rough constancy of evolutionary rate within a framework of fluctuating selection models.

Neurofibromatosis in monozygotic twins: a case report of spontaneous mutation.

Abstract: We report female monozygotic twins with neurofibromatosis. The family history is unremarkable, and careful examination of other family members did not show evidence of the condition. It is concluded that the occurrence in this family is due to a spontaneous mutation arising in one of the parental gametes. This article examines the similarity and difference in manifestations of the disorder in this pair of monozygotic twins.

The effect of a change in mutation rate on the incidence of dominant and X-linked recessive disorders in man.

Abstract: In order to assess the impact on man of a sustained change in mutation rate that might be caused by ionizing radiation or a chemical mutagen in the environment, it is important to determine the current incidence of genetic disease, the rate at which deleterious mutations arise and the number of generations that mutations persist before eliminated by selection. From these data it should be possible to estimate both the increase in genetic disease in the first generation following the increase in mutation rate, and the rate at which a new equilibrium between mutation and selection would occur. In this paper the results of a survey to determine birth frequency, mutation rate and reproductive fitness for each of the important dominant and X-linked recessive disorders are described. It is estimated that these disorders affect about 0.6% of live-born individuals, including 0.1% of live-borns who carry a newly-arising mutation. These figures are approx. 50% lower than those used by the various committees that have assessed the genetic risk to man from ionizing radiation. If the mutation rate were to permanently double, the frequency of these disorders would be expected in increase in the first generation by 15%, to 0.7% of live-births. The increase in the first 2 generations would be 24% and a 50% increase would occur by the 9th generation. A calculation of the possible increase in dominant and X-linked recessive disorders due to exposure of a population to ionizing radiation indicates that the estimate made in 1977 by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) may be too high by a factor of 2-6 fold.

Cold-Sensitive Mutation ofPseudomonas putida Affecting EnzymeSynthesis atLowTemperature

Abstract: A cold-sensitive mutant of Pseudomonas putida has been isolated which grows normally at 30 C but is unable to grow on mandelate as a source of carbon at 15 C. The mutation results in the inability of the strain to carry out the reaction catalyzed by cis,cis-muconate lactonizing enzyme at low temperature and must lie in the structural gene for that enzyme, because the mutant enzyme produced at 30 C shows altered thermal stability. The mutant enzyme is not intrinsically cold-labile, nor is it cold-labile at the moment of synthesis. The activity of the mutant enzyme is not inhibited at low temperature. Evidence is presented to establish that this mutation in the structural gene coding for cis,cis-muconate lactonizing enzyme results in the lack of expression of that gene at low temperature.

A mutation affecting L-serine and energy metabolism in E. coli K12

Abstract: The effects of a pleiotropic mutation ssd are described. This mutation results in decreased efficiency in the use of glucose and fructose as carbon source, inability to use succinate or to grow anaerobically, an alteration in the activity of enzymes responsible for the synthesis and degradation of L-serine, increased resistance to certain antibiotics, and a deficiency in proline transport. This mutation resembles various previously described mutations throught to affect ‘energy coupling factor’ and is located in the same region of the chromosome. While the gene product affected by this mutation is still unidentified, it is clear that L-serine metabolism cannot be understood merely in terms of providing L-serine and its derivatives.

Assigning a probability for paternity in apparent cases of mutation

Abstract: Any direct estimator of mutation in a human population is subject to error due to nonpaternity. This paper deals with the quantification of this error by producing, under certain assumptions, the probability for paternity. In addition, a new direct estimator of the mutation rate is introduced.