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Showing papers on "Mutation (genetic algorithm) published in 1983"


Journal ArticleDOI
TL;DR: The mean number of substitutions that will occur before the most fit allele is fixed is shown to be (formula; see text) when selection is strong and mutation is weak, independent of the parameters that went into the model.

272 citations


Journal ArticleDOI
16 Jun 1983-Nature
TL;DR: The results show that the transposon Tn10 confers an advantage by increasing the mutation rate of the host bacterium in chemostats, and this advantage is frequency-dependent.
Abstract: Strains of the bacterium Escherichia coli habouring genes that increase mutation rates are known to have an evolutionary advantage in chemostat competition over otherwise isogeneic strains with lower mutation rates1–3. This advantage is frequency-dependent, the mutator strain being favoured only above a starting ratio of ∼5×10−5, and it results from the fact that the necessary beneficial mutations cannot be generated in a mutator population below a certain size3. Here we consider the possibility that the mutagenic4,5 properties of transposable elements confer an advantage in the same manner as mutator genes. A previous report has shown that the transposon Tn5 increases the fitness of E. coli in chemostats, although the reason for this effect has not been established6. Our results show that the transposon Tn10 also confers an advantage in chemostats. In addition, we find that (1) this advantage, like that associated with mutator genes, is frequency-dependent, (2) whenever the Tn10 strains win, a segment of Tn10, probably its IS10 sequences, has undergone transposition to a new site, (3) the new insertions converge into a site contained within a 3.2 kilobase (kb) PvuII fragment of the genome, and (4) no transpositions are detected when the Tn10 population lses. We conclude that Tn10 confers an advantage by increasing the mutation rate of the host bacterium.

180 citations


Journal ArticleDOI
TL;DR: This work investigated a method employing synthetic oligonucleotides for the prenatal diagnosis of β-thalassemia due to a single nucleotide mutation and found it to be feasible and effective.
Abstract: We investigated a method employing synthetic oligonucleotides for the prenatal diagnosis of β-thalassemia due to a single nucleotide mutation. The β0 thalassemia we tested is produced by a...

174 citations


Journal ArticleDOI
10 Jun 1983-Science
TL;DR: The point mutation affecting the 12th amino acid of the c-Ha-ras gene product, while a valuable model for carcinogenesis, does not appear to play a role in the development of most human epithelial cancers of the bladder, colon, or lung.
Abstract: A point mutation alters the 12th amino acid of the c-Ha-ras oncogene product p21 in a human bladder cancer cell line. This is, at present, the only mutation known to result in a human transforming gene. This mutation may therefore represent a possible target for mutagenesis leading to carcinogenesis in humans. By means of restriction enzyme analysis, 29 human cancers, including 20 primary tumor tissues, derived from organs commonly exposed to environmental carcinogens, were tested for the presence of this mutation. None of ten primary bladder carcinomas exhibited the mutation; nor did nine colon carcinomas or ten carcinomas of the lung. Thus the point mutation affecting the 12th amino acid of the c-Ha-ras gene product, while a valuable model for carcinogenesis, does not appear to play a role in the development of most human epithelial cancers of the bladder, colon, or lung.

155 citations


Book
01 Jan 1983

122 citations



Journal ArticleDOI
TL;DR: Under these assumptions a true boundary layer dynamics emerges with rare alleles remaining near zero for an exponentially distributed length of time; thereafter they enter the interior of the allelic frequency space where natural selection alone operates at a much faster time scale than occurs in the boundary layer.
Abstract: Some general properties of populations experiencing strong selection (α = 2NS ≫ 1) and weak mutation (Θ = 4NU ≪ 1) with k ≪ ∞ alleles are described. Under these assumptions a true boundary layer dynamics emerges with rare alleles remaining near zero for an exponentially distributed length of time; thereafter they enter the interior of the allelic frequency space where natural selection alone operates at a much faster time scale than occurs in the boundary layer. This structure allows a much simpler description of the evolutionary process than by the conventional diffusion analysis. Particular models examined include overdominant selection and selection in a randomly fluctuating environment. For the latter model it is shown that drift and mutation can have a profound effect on the number of polymorphic alleles as suggested earlier by Nei and Takahata. The analysis indicates that a fundamental parameter is the product αΘ. If this quantity is very small, evolution effectively stagnates. If αΘ is moderate, th...

94 citations


Journal ArticleDOI
TL;DR: Some of the assumptions underlying estimates of DNA and protein sequence divergence are examined and it is shown that these conditions do not strongly affect estimates of divergence, and the binomial variance that is usually assumed for these estimates is safely conservative.
Abstract: Some of the assumptions underlying estimates of DNA and protein sequence divergence are examined. A solution for the variance of these estimates that allows for different mutation rates and different population sizes in each species and for an arbitrary structure in the initial population is obtained. It is shown that these conditions do not strongly affect estimates of divergence. In general, they cause the variance of divergence to be smaller than a binomial variance. Thus, the binomial variance that is usually assumed for these estimates is safely conservative. It is shown that variability in the mutation rate among sites can have an effect as large as or larger than variability in the mutation rate among bases. Variability in the mutation rate among bases and among sites causes the number of substitutions between two sequences to be underestimated. Protein and DNA sequences from several species are collected to estimate the variability in mutation rates among sites. When many homologous sequences are known, standard methods to estimate this variability can be used. The estimates of this variability show that this factor is important when considering the spectrum of spontaneous mutations and is strongly reflected in the divergence of sequences. Smaller variability is found for the third position of codons than for the first and second codon positions. This may be because of less selective constraints on this position or because the third position has been saturated with mutations for the sequences examined.

93 citations


Journal ArticleDOI
TL;DR: The temperature-sensitive adenovirus type 2 mutant H2ts1 is defective for polypeptide processing at the non-permissive temperature is mapped by marker rescue and DNA sequencing techniques: the mutation is a C/T transition located at map co-ordinate 61.1.

68 citations



Journal ArticleDOI
TL;DR: In this paper, a biological population with local random mating, migration, and mutation is studied, and an expression for the equilibrium probability of genetic relatedness between any two individuals as a function of their clustering distance is given.
Abstract: A biological population with local random mating, migration, and mutation is studied that exhibits clustering at several different levels. The migration is determined by the clustering rather than actual geographic or physical distance. Darwinian selection is assumed to be absent, and population densities are such that nearby individuals have a probability of being related. An expression is found for the equilibrium probability of genetic relatedness between any two individuals as a function of their clustering distance. Asymptotics for a small mutation rate u are discussed for both a finite number of clustering levels (and of total population size), and for an infinite number of levels. A natural example is discussed in which the probability of heterozygosity varies as u to a power times a periodic function of log(1/u).

Journal ArticleDOI
TL;DR: The model of effectively neutral mutations involving multiple alleles in which selective disadvantage of mutant alleles follows a Gamma distribution was used, showing that, as compared with the model of strictly neutral mutations, the present model gives the reduction of both H and V(H) and an excess of rare variant alleles.
Abstract: To investigate the pattern of allelic distribution in enzyme polymorphism, with special reference to the relationship between the mean (H) and the variance (VH) of heterozygosity, we used the model of effectively neutral mutations involving multiple alleles in which selective disadvantage of mutant alleles follows a Γ distribution. A simulation method was developed that enables us to study efficiently the process of random drift in a multiallelic genetic system and that saves a great deal of computer time. It is an improved version of the pseudosampling-variable (PSV) method [Kimura, M. (1980) Proc. Natl. Acad. Sci. USA 77, 522-526] previously used to simulate random drift in a diallelic system. This method will be useful for simulating many models of population genetics that involve behavior of multiple alleles in a finite population. By using this method, it was shown that, as compared with the model of strictly neutral mutations, the present model gives the reduction of both H and VH and an excess of rare variant alleles. The results were discussed in the light of recent observations on protein polymorphism with special reference to the functional constraint of proteins involved.

Book ChapterDOI
R. A. Ennos1
TL;DR: The presence of genetic variation within populations is a prerequisite for adaptation and evolutionary change and a selective explanation for the maintenance of this variation must be sought.
Abstract: The presence of genetic variation within populations is a prerequisite for adaptation and evolutionary change. All genetic variation is ultimately generated through mutation. If a mutation has no effect on the fitness of individuals, the frequency of the mutant in the population will be determined by stochastic factors [a subject thoroughly dealt with by Wright (1969)]. On the other hand, where significant amounts of genetic variation affecting fitness are found in natural populations, a selective explanation for the maintenance of this variation must be sought.



Journal ArticleDOI
TL;DR: No unequivocal new mutation was identified among 101 kindreds containing 418 affected persons, which supports the extreme rarity of mutation in Huntington's chorea.
Abstract: A study of mutation, biological fitness, and patterns of family building in Huntington's chorea has been carried out, based on a previously reported population study of the disorder in South Wales. No unequivocal new mutation was identified among 101 kindreds containing 418 affected persons, which supports the extreme rarity of mutation in this disorder. Increased values of fertility and fitness were found, both in relation to unaffected relatives and to the general population of the area. The proportion of unmarried persons and pattern of family building was comparable in affected and unaffected subjects, and no correlation with age at onset or mode of clinical presentation could be found.

Journal ArticleDOI
TL;DR: The inheritance and developmental effects of a new recessive mutation in the mouse, blind-sterile, are described, which causes lenticular cataracts and glossy coat in males and females and sterility in males due to arrested spermatogenesis.
Abstract: The inheritance and developmental effects of a new recessive mutation in the mouse, blind-sterile (bs), are described. This mutation causes lenticular cataracts and glossy coat in males and females and sterility in males due to arrested spermatogenesis. Blind-sterile is located on chromosome 2, near agouti.

Patent
30 Dec 1983
TL;DR: In this article, the authors present a vaccine for temperature-resistant pseudorabies virus which fails to produce any functional TK as a result of mutagen-induced mutation and temperature-resistance pseudoraby virus which failed to produce functional Tk as a consequence of a deletion in the tk gene.
Abstract: Temperature-resistant pseudorabies viruses which fail to produce any functional TK as a result of mutagen-induced mutation and temperature-resistant pseudorabies viruses which fail to produce any functional TK as a result of a deletion in the tk gene, vaccines containing same, methods for production of same and methods for use of same.



Journal ArticleDOI
TL;DR: In this article, the authors use extrapolations of dose: mutation ratios in other species to estimate human mutation frequencies, based on extrapolation of dose-dependent mutation ratios of other species.
Abstract: Strategies for estimating human mutation frequencies can be based on extrapolations of dose: mutation ratios in other species.




Book ChapterDOI
TL;DR: This discussion is about tools to analyze the complex relationship between chemicals and mutation in a relatively simple biological system: the exponentially growing single cell population.
Abstract: This discussion is about tools to analyze the complex relationship between chemicals and mutation in a relatively simple biological system: the exponentially growing single cell population. Three assumptions are made about this relationship: that some DNA adducts are premutagenic lesions, that adducted DNA may be repaired, misrepaired or unrepaired at the time of DNA synthesis and that unrepaired DNA may be replicated, misreplicated or unreplicated at the time of mitosis. These three assumptions lead to the definition of variables ascertainable by experimental measurement which, in turn, lead to explicit formulae which should be useful as guides in the analysis of dose(adduct) -response(mutation) relations.

Journal ArticleDOI
TL;DR: It is impossible at present to explain how such a subtle alteration can have such profound effects on this protein, and in turn, on cellular physiology, but a remarkably simple mechanism was revealed within the last year.
Abstract: Gene transfer experiments have made it possible to detect active transforming sequences in the DNA of various human tumor cells. These sequences, the cellular oncogenes, have been found in tumors as diverse as neuroblastomas, leukemias, carcinomas, and sarcomas . They appear to represent molecular determinants that participate in transformation mechanisms that are common to a wide variety of tumors . From this perspective, cancer seems to be a single, unitary disease, and not 100 different diseases, each characterized by a different type of tumor. Several ofthese oncogenes have been isolated by molecular cloning (1-4) . The most well studied of these is one from a human bladder carcinoma cell line, referred to as T24/EJ . Use of this oncogene in sequence hybridization has revealed a property common to this and the other cellular oncogenes : these oncogenes derive from closely related antecedent genes residing in the normal cellular genome . It appears that these normal genes, often called \"proto-oncogenes,\" become converted into oncogenes via processes of \"somatic mutation.\" This last conclusion remains equivocal, if only because there is little direct evidence to date showing comparison of the oncogene of a tumor with the homologous sequences of closely lying normal tissue . A variety of mechanisms might be imagined to be responsible for the conversion of a proto-oncogene into an active oncogene. In the case of the bladder carcinoma oncogene, a remarkably simple mechanism was revealed within the last year . Comparison ofthe bladder carcinoma oncogene with its normal antecedent showed that a single nucleotide alteration, occurring in the protein-encoding portion of the gene, was responsible for the activation . This point mutation affected the twelfth amino acid of the encoded 21,000-dalton protein causing the replacement of a glycine by a valine (5-9). Since little is known about the functioning of this protein, it is impossible at present to explain how such a subtle alteration can have such profound effects on this protein, and in turn, on cellular physiology . This bladder carcinoma proto-oncogene has homologs in the DNA of all vertebrates . Its evolutionary origins can, however, be traced back much further. Sequence hybridization has found homologs of this and other proto-oncogenes PERSPECTIVES

Journal ArticleDOI
TL;DR: Based on the notion of comparing two proportions, a test statistic is proposed and applied to experimental results for a test of equality of mutation rates in different cell lines, which places the comparison of mutations rates on a statistical basis.
Abstract: The factors that affect reliable estimations of mutation rates (g) in cultured mammalian somatic cell populations by fluctuation analysis are studied experimentally and statistically. We analyze the differential effect of the final cell population size in each culture (N t) and the number of parallel cultures (C) on the variation in the rate estimates (tl) inferred from the P0 method. The analysis can be made after the derivation of the variance of/i, which is a measure of variation of tl for a given combination of N t and C in a number of repeat experiments. The variance of ti is inversely proportional to C and to the square of N t. N t determines the probability of occurrence of mutations in a cell culture. By influencing the size of P0, Nt also determines whether a rate estimate is obtainable from the experiment. Since Po is estimated from the fraction of cultures containing no mutation in a set of C cultures, C becomes a determining factor for the accuracy of/2. The rate estimated from/5 o is biased, but the bias is in general 2 orders of magnitude smaller than /i. By the selection of an appropriate combination of N t and C for the experiment, this bias can be reduced even further. Based on the notion of comparing two proportions, we propose a test statistic and have applied it to experimental results for a test of equality of mutation rates in different cell lines. This development places the comparison of mutation rates on a statistical basis. Since the publication of Luria and Delbriick's paper [19] on the distribution of the number of mutant colonies in a series of parallel cultures, fluctuation analysis has been widely applied as a method for the determination of mutation rates (#) in cell populations. The analysis has since been further developed methodologically by Lea and Coulson [15], Newcombe [22], and Armitage [2,3] and modified theoreti

Journal ArticleDOI
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for blood coagulation preoperatively on the basis of prior history and once they provide informed consent for surgery.
Abstract: Hemorrhage resulting from genetic defects in the blood coagulation system represents one of the most dramatic clinical emergencies Study of these disorders has led to effective approaches for both