Showing papers on "Mutation (genetic algorithm) published in 1976"

Genetic Polymorphism in Heterogeneous Environments

Abstract: The discovery in the last decade, using electrophoresis, of large amounts of genetic polymorphism in natural populations has had a tremendous effect on population genetics. Before then it was not clear how many polymorphic loci there were in a population and the single gene overdominance model generally seemed adequate to explain what polymorphism was documented. In an effort to explain the new-found genetic variation, two opposing camps surfaced in the late 1960s and still exist to some extent today. One group, often called neutralists, believes that most allozymic variants have a minimal effect on fitness and are in a population because of a combination of mutation, finite population size, and migration. In other words, in their view, selection plays little or no role in maintaining different electrophoretic alleles. The other group, sometimes known as selectionists, believes that some sort of balancing selection is responsible for the maintenance of the majority of electropho­ retic alleles. "Balancing selection" is a catch all term for any type of selection that can maintain a stable polymorphism. Among the types of balancing selection that are thought to play a significant role in maintaining genetic polymorphisms are the classical overdominance mode, frequency-dependent selection [see (8) for a recent review], differential selection between the two sexes or between different life stages, and variable selection in time and/or space. This last type of balancing selection is examined here in an effort to understand the importance of selection varying in time and/or space in maintaining genetic polymQrphisms. A significant body of literature demonstrates an association between the genetic attributes of a population and some aspect of the environment. Since much of this material has been reviewed elsewhere (2, 16,58, 165), we concentrate on two of the

Infinite allele model with varying mutation rate

Abstract: Available data suggest that the variation in mutation rate among protein loci follows the gamma distribution. Thus, taking into account this variation, formulae are developed for the distribution of allele frequencies, mean and variance of heterozygosity, expected number of alleles, proportion of polymorphic loci, and genetic distance. These formulae should be more appropriate for the analysis of gene frequency data for protein loci than equivalent formulae with constant mutation rate.

Regulation of arginine biosynthesis in Saccharomyces cerevisiae: isolation of a cis-dominant, constitutive mutant for ornithine carbamoyltransferase synthesis.

Abstract: A cis-dominant mutation linked to argF, the structural gene specifying ornithine carbamoyltransferase, and affecting the control of the synthesis of this enzyme has been obtained. The level of ornithine carbamoyltransferase in this mutation is depressed and less repressible by addition of L-arginine than it is in the wild-type strain. Of 38 tetrads analyzed, resulting from a cross of a strain harboring this mutation with a strain carrying an argF- mutation, none was a tetratype or a nonparental ditype. This operator mutation helps to define a negative mode of control of the synthesis of the arginine biosynthetic enzymes, as had been suggested earlier upon the isolation of argRI- (arg80), argRII- (arg81), and argRIII- (arg82) specific regulatory mutations.

Heat mutagenesis in bacteriophage T4: the transition pathway.

Abstract: G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation.

Serologic and Genetic Aspects of Murine Ia Antigens

Abstract: The Ir-1 locus controls immune responses to synthetic polypeptides T,G (A-L), H,G (A-L) and (Phe,G) A-L. The mapping of this locus within the H-2-gene complex^ (McDevitt et al. 1972) intensified efforts to identify the Ir-gene product. Furthermore, the major factors influencing the MLR (mixed lymphocyte reaction) and the GVH (graft-versus-host reaction) were found to be controlled by gen^s mapping between the H-2K and Ss loci, emphasizing the importance of this chromosomal segment in immune phenomenon (Bach et al. 1972, Klein & Park 1972, Meo et al. 1973a). The availability of a pair of intra-H-2 recombinant lines, A.TL and A.TH, which are identical at the H-2K and H-2D regions but which are different in the central regions of the H-2 complex, have facilitated the identification of the Ir-gene product (David & Shreffler 1972a). The identification, characterization, and related aspects of the Ir-associated antigen system will be described in this review.

Directed selective pressure on a β-lactamase to analyse molecular changes involved in development of enzyme function

Abstract: Directed selective pressure on a β-lactamase to analyse molecular changes involved in development of enzyme function

The biological origin of antibody diversity.

Abstract: Antibody diversity has a compelling fascination for many scientists and over the years speculations have sometimes seemed more numerous than facts. Now the structural basis of antibody specificity is well defined. Amino acid sequences and recently three-dimensional structures of various immunoglobulins provide the most solid basis for discussing the origin of diversity. The novel pattern of variable (V) and Constant (C) regions of amino acid sequence has been resolved further to show the functional pattern of variability. Inheritance of separate V and C genes is accepted, but attempts to define more than one gene coding for each V region are considered here to be unnecessary. The pattern of variability is still best understood in terms of mutation and the presence or absence of various selective pressures. The major area of debate still hinges around the extent to which mutation and selection operate during evolution or somatically. Sequence data have now been generally interpreted to require multiple V genes carried in the germ line. A few individual VH genes have been mapped in close linkage to CH genes in the mouse. The apparent existence of three VH alleles in rabbits was a strong argument against multiple V genes. Now the three phenotypes have been shown to be due to alleles controlling the expression of three sets of VH genes all present on the same chromosome. That V-gene expression requires rejoining of V and C genes at the DNA level is now almost certain. Models for the joining process can draw on the precedents of transposable genetic elements, which are widespread in Nature. The total extent of antibody diversity remains a philosophical point. Estimates of the number of antibody molecules required for observed diversity are reduced by two recently documented proposals. Each antibody combining site apparently has many (estimated at 100) different specificities and most combinations of VH and VL regions probably form a viable site. A given combining site can be defined by its pattern of shared specificities. Several specific antibody repertoires have been measured and the size in each case is consistent with the stringency with which the specificity is selected. Repertoire size appears to be under genetic control, but there are problems in viewing the genotype through the veil of clonal selection. Molecular hybridization has been used recently in an attempt to count V and C genes directly. C genes are seen in DNA having nonreiterated sequences, as formal genetics predicts. Each V-region probe hybridizes at a similar rate to C-region probes. Interpretation of this result depends on the extent to which one V-region probe will reveal nonhomologous V genes. Previous estimates that many cross-hybridizing genes should have been seen if present are possibly exaggerated. It is argued here that the data are compatible with a germ-line gene for each probe studied. Maximum estimates for the number of germ-line genes are sufficient to account for antibody diversity...

Global stability of genetic systems governed by mutation and selection. II

Abstract: An infinite genetic population of haploid particles is considered in which selection is controlled by a single locus at which there are an infinite number of possible alleles. These alleles are arranged in an infinite sequence and mutation occurs only to nearest neighbours. This is the ‘ladder model’ of Ohta and Kimura which was put forward as a possible explanation of the distributions of electromorphs in electrophoretic observations. Following an earlier paper, conditions are obtained on the selection coefficients which ensure that a stationary stable state exists. One such model is solved explicitly. The problem, important in evolutionary theory, of the rate of approach to such stationary states starting from some other state, is also discussed briefly.

The transient distribution of allele frequencies under mutation pressure.

Abstract: The transient distribution of allele frequencies in a finite population is derived under the assumption that there are k possible alleic states at a locus and mutation occurs in all directions. At steady state this distribution becomes identical with the distribution obtained by Wright, Kimura and Crow when k = ∞. The rate of approach to the steady state distribution is generally very slow, the asymptotic rate being 2v + 1/(2N), where v and N are the mutation rate and effective population size, respectively. Using this distribution it is shown that when population size is suddenly increased, the expected number of alleles increases more rapidly than the expected heterozygosity. Implications of the present study on testing hypotheses for the maintenance of genetic variability in populations are discussed.

The fluctuation test as a more sensitive system for determining induced mutation in l5178y mouse lymphoma cells.

Abstract: Luria-Delbruck fluctuation tests for the determination of the spontaneous mutation rate to ouabain resistance incultured L5178Y mouse lymphoma cells gave values in the range 0.44 to 1.03 X 10(-7) mutants per cell per generation. Addition of very low, non-toxic, levels of EMS (0.1 mM) and MMS (0.012 mM) 30-48 h before plating in selective medium gave a highly significant increase in the number of ouabain-resistant mutants. Methods for the calculation of spontaneous and induced mutation rates are discussed and a method for the computation of induced mutation rates is described. It is suggested that the modified fluctuation test is a simpler and considerably more sensitive assay for mutagens than the conventional experimental design. Some of its limitations are discussed.

Cooperative control of translational fidelity by ribosomal proteins in Escherichia coli. III. A ram mutation in the structural gene for protein S5 (rpx E).

Abstract: The effect on translational fidelity of a particular mutation in the gene coding for protein S5(rpxE) has been investigated. This mutation has the opposite effect of a restrictive strA mutation; in vivo, it relieves the restriction imposed by strA on the suppression of T4 nonsense mutants and results in hypersensitivity to streptomycin; in vitro, the presence of the altered S5 protein in 30S ribosomes results in increased intrinsic misreading. It is concluded that this mutation, ramC319, acts as a ribosomal ambiguity mutation similar to certain mutations of protein S4 (ramA).

Old World Monkey Hemoglobins: Deciphering Phylogeny from Complex Patterns of Molecular Evolution

Abstract: Some of the pertinent questions being addressed by those carrying out research in molecular anthropology can be summarized as follows: 1. Are most of the DNA mutations that become fixed selectively neutral (or almost so)? 2. What effect do gene duplications have on the rate of mutation acceptance? 3. Can cladistic relationships of use to taxonomists be elucidated, despite any limitations arising from (1) and (2)? 4. If so, is the minority view that proteins can be used as “molecular clocks” tenable?

Characterization of a unique lethal tumorous mutation in Drosophila.

Abstract: Spontaneous and induced mutations producing melanotic tumors in D. melanogaster have been reported by several different investigators [1]. These tumors, except for variations with respect to the type of tissues that house the tumors, display a common set of characteristics. Normally, the growth pattern of the tumor is restricted to small growths that, depending upon the specific genetic and environmental parameters, reach predictable sizes and patterns of distribution throughout the abdomen of the fly [2, 3]. The genetic component controlling these tumors are generally polygenic in structure. By examining the importance of the different activities of the genes making up the polygenic system, it is possible to subdivide the genes into major and minor genes. The major genes are responsible for the development of the tumor while the minor genes influence the frequency of the tumors. In an article surveying a large number of Drosophila tumors, Barigozzi presents data demonstrating that, for the tumors examined, genetic control consists of at least two polygenic systems [2]. One polygenic system apparently triggers the proliferation of the lamellocytes and the other system controls the initiation of melanization. Almost without exception, these polygenic systems were located on the second chromosome with a few residing on the third chromosome. In Barigozzi's study and for those tumors reported in Lindsley and Grell [4], the tumorous condition has been found to be recessive visible, having only occasional mild effects in the heterozygous condition. Finally, almost all of the effects of tumor causing genes have been shown to be temperature sensitive. The effect that temperature has on the frequency of occurrence of tumors differs with different strains of Drosophila. However, generally higher temperatures decrease the incidence of tumors [3]. In contrast to the above set of attributes, a melanotic

A single mutation hypothesis for multiple sclerosis based on the HL-A system.

Abstract: No. 21

Population genetics of Alport's syndrome. Hypothesis of abnormal segregation and the necessary existence of mutation.

Abstract: The diagnosis of Alport's syndrome is generally not considered in the absence of a positive family history. Family studies indicate that transmission occures by a rare autosomal dominant gene. The deviation of transmission ratios from the classical Mendelian pattern is best explained by abnormal segregation. Based on observed pedigree data, calculations were made of the expected equilibrium population frequency of Alport's syndrome assuming mutation rates of zero, 10, and 50 per million gametes. Zero mutation rate should result in disappearance of the Alport gene. An equilibrium frequency corresponding to that actually observed in Rhode Island implies a mutation rate of 10 per million gametes. Furthermore, up to 18% of all newborns with the Alport genotype may represent new mutants. Thus, isolated cases of Alport's syndrome may occur in the absence of other affected family members.

A Mixed Model of Mutation for Electrophoretic Identity of Proteins within and between Populations.

Abstract: A model which is a mixture of the model of infinite alleles and the Ohta-Kimura model of stepwise mutation has been proposed for the study of eletcrophoretic variants in natural populations. Mutations which alter the mobility of a protein are divided into two classes: stepwise mutations and nonstepwise mutations. It is assumed that stepwise mutations follow the Ohta-Kimura model while nonstepwise mutations follow the infinite allele model. It is then shown that even if the proportion of nonstepwise mutations is only 5%, with the other 95% stepwise mutations, the effective number of alleles given by the present model is considerably larger than that given by the Ohta-Kimura model of stepwise mutation. The result has also been applied to study Nei's genetic distance.

Mutation and Molecular Evolution

Abstract: The mutation process provides all the genetic variants from which evolution selects the most useful in order to produce the present-day diversity of living organisms. Until recently, evolution theoreticians have taken mutation more or less for granted, concentrating mainly on the theory of natural selection. The founders of the concept of molecular evolution on the one hand and Kimura (1968) with his theory of neutrality on the other have directed the interest of theoreticians toward mutation again. In view of the considerable amount of experimental work with different species, one would expect that theories in this field should be backed by a very detailed knowledge of the conditions under which mutations occur in nature. Surprisingly, however, this is not the case: most experimental work has been done on mutations which were induced either by ionizing radiation or by chemical compounds. From this type of work, only very limited information can be gained concerning spontaneous mutation. In addition, such research is usually carried out more or less as a sideline of other work. Molecular biology has taught us that the observed mutations, even if they can be traced down to the level of the polypeptide chain, are the end result of a complex interaction of primary events which are under genetic control. We should also consider the primary changes in the DNA, the probability of which depends on metabolic differences, the efficiency of polymerases, etc. How many of these changes will finally become visible as mutations depends on the efficiency of repair processes. However, polymerases, as well as repair processes, are under genetic control (cf. Drake, 1973).