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Showing papers on "Mutation (genetic algorithm) published in 1980"


Journal ArticleDOI
01 Jan 1980-Genetics
TL;DR: Approximate expressions for the dynamics of the genetic covariances due to pleiotropic mutations are obtained and patterns of genetic covariance between characters and their evolution are discussed with reference to data on polygenic mutation, chromosomal organization and morphological integration.
Abstract: A statistical genetic model of a multivariate phenotype is derived to investigate the covariation of pleiotropic mutations with additive effects under the combined action of phenotypic selection, linkage and the mating system. Equilibrium formulas for large, randomly mating populations demonstrate that, when selection on polygenic variation is much smaller than twice the harmonic mean recombination rate between loci with interacting fitnesses, linkage disequilibrium is negligible and pleiotropy is the main cause of genetic correlations between characters. Under these conditions, approximate expressions for the dynamics of the genetic covariances due to pleiotropic mutations are obtained. Patterns of genetic covariance between characters and their evolution are discussed with reference to data on polygenic mutation, chromosomal organization and morphological integration.

593 citations


01 Jan 1980
TL;DR: An empirical study of several factors important in the feasibility and reliability of mutation analysis and a study of mutagenic operator efficiencies indicates that mutation analysis can be performed on compiled programs, rather than being limited to interpretive execution.
Abstract: Program mutation has been advanced by DeMillo et. al. as a powerful program testing technique. The present work is an empirical study of several factors important in the feasibility and reliability of mutation analysis. In the course of investigating the coupling effect, over a million complex mutants were subjected to test data sufficient for first order mutation. All but 45 of these were either eliminated by the test data or proved to be equivalent to the original programs. Most of the 45 could be addressed within the framework of mutation analysis by the addition of a new mutagenic operator. An experiment on the human evaluation of equivalence (of mutants to original programs) produced inconclusive results, but indicates the need for caution in the practice of mutation analysis in the step of judging mutants equivalent. A study of mutagenic operator efficiencies indicates that mutation analysis can be performed on compiled programs, rather than being limited to interpretive execution.

545 citations


Journal ArticleDOI
01 Dec 1980-Genetics
TL;DR: The observed selection is due to the allozymes themselves (or to associated regulatory elements), as the selection disappears when the chemostats are limited by a different carbon source (ribose plus succinate).
Abstract: We have used gluconate-limited chemostats to study selective differences between isogenic strains of Escherichia coli K12 into which four naturally occurring alleles coding for allozymes of 6-phosphogluconate dehydrogenase (6PGD) had been transferred. The limit of detectability of selection with our procedures is a selection coefficient of 0.5%. In the normal E. coli K12 genetic background, all alleles are selectively neutral or nearly neutral. The absence of detectable selection does, however, depend on genetic background and on such environmental factors as cell density. In a genetic background containing a mutation that cuts off the alternative metabolic route for 6-phosphogluconate, selection between allozymes can be detected, and the selection is in the direction expected from the measured apparent K m values of the allozymes. Even when the alternative metabolic route is not blocked by mutation, one of the 6PGD allozymes has a detrimental, but density-dependent, interaction with a mutation conferring resistance to bacteriophage T5. In all cases, the observed selection is due to the allozymes themselves (or to associated regulatory elements), as the selection disappears when the chemostats are limited by a different carbon source (ribose plus succinate). Nevertheless, the four alleles do seem to be selectively neutral or nearly neutral in the normal E. coli K12 genetic background. Moreover, the distribution of allele frequencies in natural populations of E. coli is in accord with the expectations of selective neutrality. I am inclined to suspect that we see, at least in some [cases], variations which are of no service to the species, and which consequently have not been seized on and rendered definite by natural selection…. Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed…. We may easily err in attributing importance to characters, and in believing that they have been developed through natural selection;… many structures are now of no direct use to their possessors, and may never have been of any use to their progenitors…. [On the other hand,] we are much too ignorant in regard to the whole economy of any organic being to say what slight modifications would be of importance or not.

184 citations


Journal ArticleDOI
01 May 1980-Plasmid

114 citations


Book
01 Jan 1980
TL;DR: In this article, a general model for mutation in finite populations is proposed, based on the Wright-Fisher model. But the model does not consider the effect of mutation in the absence of selection.
Abstract: The Problem: Why Mathematics? Genes and Their Inheritance, Selection, Mutation Survival of the Fittest: Balanced Polymorphisms, Multi-Locus Selection, Balance Between Selection and Mutation, The House of Cards, The Diploid House of Cards, The Resistance of Polymorphisms to Mutation The Neutral Alternative: Evolution in the Absence of Selection, A General Model for Mutation in Finite Populations, The Random Walk Case, The Frequency Spectrum, The Ewens Sampling Formula, The Poisson-Dirichlet Distribution, Partition Structures, Testing Neutrality Selection in Finite Populations: Deleterious Mutants, The Wright-Fisher Model, Wright's Formula, The Infinite Alleles Limit.

107 citations


Journal ArticleDOI
01 Aug 1980-Cell
TL;DR: The his4-912 mutation shares similar genetic properties with mutations promoted by procaryotic insertion elements, but this mutation lacks all three his4 functions.

104 citations


Journal ArticleDOI
TL;DR: The numbers of patients with major thalassemic diseases examined in the department of medicine and pediatrics are shown, exclusive of the Hb Bart's hydrops fetalis.
Abstract: In Thailand, a and B thalassemia, hemoglobin (Hb) E, and Hb Constant Spring (Con Sp) are The frequencies are 20%-30% for a thalassemia, 3%-9% for thalassemia, up to 52% for Hb E and at least 4% for Hb Con Sp. The abnormal genes in different combinations lead to over 60 thalassemic syndromes. TABLE 1 shows the numbers of patients with major thalassemic diseases examined in our unit, exclusive of the Hb Bart's hydrops fetalis. This is in the department of medicine; in the department of pediatrics of this hospital they have seen more or less the same numbers of thalassemic patients. Clinical features, although of extreme interest, will not be described here; however, certain other salient points will be discussed.

104 citations



Journal ArticleDOI
TL;DR: A novel type of regulatory mutation for galactose metabolism in Saccharomyces cerevisiae is described, which caused a ‘coordinate’ reduction of galactokinase, galactOSE-1-P uridylyl transferase, and UDP-glucose 4-epimerase, rendering the mutant cells Galactose-nonfermenting.
Abstract: A novel type of regulatory mutation for galactose metabolism in Saccharomyces cerevisiae is described. The mutation named gal11 was recessive, non-allelic to GAL4, GAL80, GAL2, or GAL3, and unlinked to the gene cluster of GAL1, GAL10, and GAL7. It caused a ‘coordinate’ reduction of galactokinase, galactose-1-P uridylyl transferase, and UDP-glucose 4-epimerase by a factor of more than 5, rendering the mutant cells galactose-nonfermenting. The effect of the mutation was manifested not only in cells grown on galactose but also in cells constitutively synthesizing the galactose-metabolizing enzymes.

59 citations


Journal ArticleDOI
01 Nov 1980-Politics

55 citations



Journal ArticleDOI
TL;DR: The present theory offers a unified solution to three closely related evolutionary problems and throws light on several specific evolutionary problems, including the interpretation of genic polymorphism, the variability of evolutionary rates inferred from the fossil record, the evolution of "pseudoexogenous" and "trivial" adaptation, and the problem of speciation.
Abstract: It is customary to distinguish between primary genes and modifier genes. Some modifier genes alter the effects of primary genes and of other modifier genes, others influence mutation and crossover rates. In the following discussion it will be convenient to classify genes in another way. (a) Genes expressed during development will be called a genes. This category includes both structural genes, coding for specific proteins, and genes that regulate and coordinate the actions of other genes. Every variation of an a gene directly affects the fitness of the genome in which it occurs. (b) Genes that specify mutation and recombination rates will be called ,8 genes. A ,8 gene or a battery of 8 genes may regulate the mutation rates of one or more a genes, the rates of one or more specific chromosomal mutations, or the crossover rates in one or more specific, narrow chromosomal regions. It may also affect the variability of another , gene. All , genes are modifiers, but not all modifiers are p genes. I shall argue that the system of p genes encodes a strategy for evolution and that this system is shaped by natural selection to increase the efficiency of the evolutionary process by (a) directing genetic variation into potentially adaptive pathways in genotype space, (b) augmenting the rates of potentially adaptive genetic variations, and (c) suppressing variation that is likely to diminish fitness. The arguments to be presented in support of these assertions rest on the fundamental Darwinian postulate that genetic variation is blind to its phenotypic consequences. They make no appeal to as-yet-undiscovered biological or physicochemical principles, nor do they invoke group selection. The plan of the paper is as follows. After briefly reviewing experimental evidence bearing on the existence of p systems in prokaryotes and eukaryotes, I consider the principle of hierarchic construction underlying the process of evolution. I then discuss the role of p genes in hierarchic construction, and argue that hierarchic construction is itself a ,8 adaptation. Finally, I apply the present theory to a number of evolutionary problems: the interpretation of genic polymorphism, the variability of evolutionary rates, pseudo-exogenous and trivial adaptations, and the problem of speciation.

Journal ArticleDOI
TL;DR: The A/Victoria/75-ts-l A2 recombinant proved to be more attenuated and more stable genetically in hamsters, adults, and children than a series of ts-1 [El recombinants studied previously], and single-lesion ts mutants, which exhibited an unusual degree of genetic stability.
Abstract: Genetic instability represents one of the major obstacles impeding current efforts to develop safe, effective mutants for use in live virus vaccines. Although certain temperature-sensitive (1s) and cold-adapted ( c a ) mutants, with defined mutations responsible for attenuation, have been shown to be safe and immunogenic in man, on occasion infected individuals have yielded virus with altered ts or ca This type of genetic instability has been observed most frequently during unrestricted viral replication in a completely susceptible For example, the influenza A/Hong Kong/68-ts-l [El (H3N2) recombinant, which exhibited ii 38\" C shutoff temperature for plaque formation, retained its ts phenotype after replication in adult volunteers who had detectable immunity to the viral neuraminidase surface-glycoprotein but not to the viral hemagglutinin surface-gly~oprotein.~. In contrast, when the ts-1 [El recombinant was given to young vaccinees who had not been previously infected with an influenza A virus, 25% of these individuals shed virus that had lost its temperature sensitivity ( t ~ ) .1 In an attempt to produce a ts virus more stable than the influenza A/Hong Kong/68 ts-1 m] donor, two single-lesion ts mutants, which exhibited an unusual degree of genetic stability. were mated and their rs genes were transferred into a recombinant.? The resulting influenza A/ Udorn/ 72-ts-1A2 recombinant possessed ts mutations on the P3 and P1 polymerase genes and exhibited a 37\" C shutoff temperature for plaque f~ rma t ion .~ , * The two mutant genes were then transferred by genetic reassortment to the influenza A/Victoria/ 75 (H3N2) wild-type virus.9 The A/Victoria/75-ts-l A2 recombinant proved to be more attenuated and more stable genetically in hamsters, adults, and children than a series of ts-1 [El recombinants studied previously. (Wright, et al. Un-

Journal ArticleDOI
TL;DR: The concept that new genes can be inserted into living animals is relatively new, but the phenomenon of transmission of genetic material from one organism into the genome of another has probably existed since the early stages of evolution.
Abstract: The concept that new genes can be inserted into living animals is relatively new, but the phenomenon of transmission of genetic material from one organism into the genome of another has probably existed since the early stages of evolution. Mutation of nucleotide sequences in the DNA code has long been seen as the principal mechanism of evolutionary adaptation, while transmission of genetic materials between species was considered to be a rare event. This conventional view requires revision in the light of recent knowledge about genetic elements adapted for shuttling between different regions of a single genome or between different genomes. . . .

Journal ArticleDOI
TL;DR: It is argued that the single locus affected is the structural gene for the sigma subunit of E. coli RNA polymerase, which renders sigma about 10-fold more thermolabile than the wild type sigma at 45°C in vitro.
Abstract: We have characterized a new mutation rpoD800 affecting the sigma gene of E. coli. Upon transfer to high temperature, a strain with the rpoD800 mutation ceases growth within 30 min. We find that this mutation renders sigma about 10-fold more thermolabile than the wild type sigma at 45°C in vitro. We have compared the temperature profile for inactivation of wild type and mutant sigma and find that the mutant inactivates at a temperature about 9° C lower than does the wild type.


Journal ArticleDOI
TL;DR: A mutation found in many strains of the Y10 line of Escherichia coli K-12, but not previously described, maps at 27 min, close to galU, which causes mucoidity or uracil requirement at 29°C depending on the genetic background.
Abstract: cur-1, a mutation found in many strains of the Y10 line of Escherichia coli K-12, but not previously described, maps at 27 min, close to galU. cur-1 causes mucoidity or uracil requirement at 29 degree C depending on the genetic background. These phenotypes are suppressed by amber codon suppressors.

Journal ArticleDOI
TL;DR: Since not only glucose but a wide variety of nutrients affect the differential rates of synthesis of enzymes that are normally inducible, even in mutants that form these enzymes constitutively, the effect indicates a general correlation between the intensity of carbon flux through catabolic pathways and the rates at which the genes specifying these enzymes are expressed.

Journal ArticleDOI
TL;DR: Male mice which are heterozygous for a recessive lethal mutation (+/tL) transmit the tL mutation in non-Mendelian ratios in vitro and the frequency of transmission is the same as the transmission frequency of the t12 mutation in vivo when matings are delayed until the time of ovulation.
Abstract: Male mice which are heterozygous for a recessive lethal mutation (+ / t L ) transmit the t L mutation in non-Mendelian ratios. In the present studies, spermatozoa obtained from + / t 12 males were used to fertilize ova from + / t 12 females in vitro . The frequency of transmission of the t 12 mutation determined from these in vitro studies was compared with the frequency of transmission of this mutation in normal and delayed matings. The data show that the transmission frequency of the t 12 mutation, in vitro , is Mendelian and is the same as the transmission frequency of the t 12 mutation in vivo when matings are delayed until the time of ovulation.

Journal ArticleDOI
TL;DR: An assay based on forward mutation of Dictyostelium discoideum to 3% methanol resistance allows quantitation of induced mutation following treatment with physical and chemical agents and achieves plateau in the number of mutants as a function of expression time.
Abstract: An assay based on forward mutation of Dictyostelium discoideum to 3% methanol resistance allows quantitation of induced mutation following treatment with physical and chemical agents. Properties of this assay are: uniform recovery of methanol-resistant (MeOH r ) cells over a wide range of plated cell densities, equal growth rates of methanol-sensitive and methanol-resistant cells in the absence of methanol during the expression period and the attainment of plateau in the number of mutants as a function of expression time. When 4 mutagens were tested with this system and compared at the 10% survival level, N -methyl- N ′-nitrosoguanidine was the most effective for mutation induction, followed by 60 Co-γ-rays, ultraviolet light, and methyl methanesulfonate.




Journal ArticleDOI
H. Traut1
TL;DR: The procedure proposed has some advantages when compared with the 2 and the KASTENBAUM-BOWMAN test, the most important one being that it can be employed when these two tests cannot (because of expected frequencies <5 in the 2 test and limited tabulations of the N and p values in the Kastenbaum-Bowman test).
Abstract: A method is devised for determining the statistical significance of the difference between a mutation frequency observed after treatment with a potential mutagen and its control frequency. This procedure, however, can be used only when the respective control value is based on large and reliable material (“stable” controls), a requirement that seems to be met in at least part of the systems used for mutagenesis screening. The procedure proposed has some advantages when compared with the 2 and the KASTENBAUM-BOWMAN test, the most important one being that it can be employed when these two tests cannot (because of expected frequencies <5 in the 2 test and limited tabulations of the N and p values in the KASTENBAUM-BOWMAN test). After explaining the procedure, an instruction how to carry it out is presented and illustrated by two examples (recessive sex-linked lethal mutations in Drosophila melanogaster and dicentric chromosomes in human lymphocytes).

Journal ArticleDOI
TL;DR: The predicitivity and reliability of short-term tests and their ability to assess carcinogenic potency are discussed, and similar characteristics for animal carcinogenicity studies are also discussed.
Abstract: Industrial societies have developed a way of life that is increasingly dependent on artefacts produced from chemicals. The benefits that man has derived from the use of these artefacts are abundant and include the control of disease, increased agricultural production, and improved quality of life. It is only in recent years, however, that the price that society has paid in terms of damage to human health has become the subject of concern, as is evidenced by the many chemicals of unknown biological activity introduced into manufacture during the early decades of this century. A major aspect of concern about the effects of chemicals on man centres on their carcinogenicity. By definition, human carcinogens can be identified only by epidemiological studies in man, a procedure that is manifestly too late to prevent suffering. Attention has thus been concentrated on developing laboratory methods based on parameters other than human cancer, which are nevertheless capable of identifying chemicals with biological activity classifying them as candidate human carcinogens. These laboratory models include both in-vitro or \"short-term\" tests for carcinogenicity and the more conventional chronic animal studies. Laboratory models of this type have certain characteristics that define their performance and thus their utility in identifying carcinogens and their potential effects in man. This paper discusses the predicitivity and reliability of short-term tests and their ability to assess carcinogenic potency. Similar characteristics for animal carcinogenicity studies are also discussed.


Journal ArticleDOI
TL;DR: Control experiments demonstrate that the observed reductions in mutation frequency do not result from unacceptable pathways of reversion in the presence of the ts allele.


Journal ArticleDOI
TL;DR: It is shown that the frequency of these DEL1-promoted deletions is not altered by the presence of the recombination-deficient mutation, rad52-1, which indicates that generalized recombination is not required for the formation of deletions in DEL1 yeast strains.
Abstract: The DEL1 mutator in Saccharomyces cerevisiae leads to the formation of deletions adjacent to itself (Liebman et al. 1979). Here we show that the frequency of these DEL1-promoted deletions is not altered by the presence of the recombination-deficient mutation, rad52-1. This indicates that generalized recombination is not required for the formation of deletions in DEL1 yeast strains.