Showing papers on "Mutation rate published in 1980"

Rate of gene silencing at duplicate loci: a theoretical study and interpretation of data from tetraploid fishes.

Abstract: A large-scale simulation has been conducted on the rate of gene loss at duplicate loci under irreversible mutation. It is found that tight linkage does not provide a strong sheltering effect, as thought by previous authors; indeed, the mean loss time for the case of tight linkage is of the same order of magnitude as that for no linkage, as long as Nu is not much larger than 1, where N is the effective population size and u the mutation rate. When Nu is 0.01 or less, the two loci behave almost as neutral loci, regardless of linkage, and the mean loss time is about only half the mean extinction time for a neutral allele under irreversible mutation. However, the former becomes two or more times larger than the latter when Nu ≥ 1.——In the simulation, the sojourn times in the frequency intervals (0, 0.01) and (0.99, 1) and the time for the frequency of the null allele to reach 0.99 at one of the two loci have also been recorded. The results show that the population is monomorphic for the normal allele most of the time if Nu ≤ 0.01, but polymorphic for the null and the normal alleles most of the time if Nu ≥ 0.1.——The distribution of the frequency of the null allele in an equilibrium tetraploid population has been studied analytically. The present results have been applied to interpret data from some fish groups that are of tetraploid origin, and a model for explaining the slow rate of gene loss in these fishes is proposed.

Genetic divergence among fishes of the eastern pacific and the caribbean: support for the molecular clock.

Abstract: The concept of a molecular clock is certainly controversial among evolutionary biologists. Simply stated, the hypothesis predicts that the rate of amino acid substitutions between any pair of taxa is relatively regular and reflects the divergence time between the taxa. The substitutions can be measured directly, by sequencing proteins, or indirectly, by such techniques as immunological or electrophoretic comparisons. The molecular clock is a prediction of the neutrality hypothesis of molecular evolution. Under this hypothesis, the long-term rate of protein sequence evolution equals the rate of mutation which produces selectively equivalent amino acid substitutions in proteins. Since mutation rate is a stochastic process, the clock is viewed as stochastic (Kimura and Ohta, 1971). Much of the evidence in favor of the molecular clock has been reviewed by Wilson et al. (1977). By constructing phylogenetic trees from molecular data and comparing the amount of change occurring along diverging branches of the trees (relative rate test), Wilson et al. (1977) point out that one can assess the degree of regularity of molecular change between taxa. A useful clock has to be not only regular, but also must be calibrated. Calibration is not always easy to achieve, for it is dependent upon a knowledge of geological events, often the fossil record, and interpretations based upon such records are often open to considerable question (Carl-

The origin of spontaneous mutation in saccharomyces cerevisiae

Abstract: Characterization of two antimutator loci in yeast shows that both are members of the same mutagenic repair system known to be responsible for almost all induced mutation (LAWRENCE and CHRISTENSEN 1976, 1979a,b; PRAKASH 1976). One of the these newly isolated antimutator mutations is an allele of rev3 (LEMONTT 1971b). Two other alleles of rev3 were tested and were also found to be antimutators. Double mutants carrying rev3 and mutator mutations of rad3, rad51 or rad18 are like rev3 single mutants with respect to spontaneous mutation rate, supporting the hypothesis (HASTINGS, QUAH and VON BORSTEL, 1976) that many mutators in yeast act by channelling spontaneous lesions from accurate to mutagenic repair. However, the enhanced mutation rate seen in a radiation-resistant mutator mutant mut1 is not dependent on REV3, but is dependent on another gene designated ANT1. An additive effect on the reduction in spontaneous mutation, seen in the ant1 rev3 double-mutant strain, leads to the conclusion that at least 90% of spontaneous mutations seen in the wild type are caused by mutagenic repair of spontaneous lesions.

Spontaneous Allozyme Mutations in DROSOPHILA MELANOGASTER: Rate of Occurrence and Nature of the Mutants.

Abstract: After additional generations of accumulation of allozyme mutants, the 1,000 lines of Mukai and Cockerham (1977) were again screened for the same five loci (α-Gpdh, cMdh, Adh, Hex-C and α-Amy), as well as for two new loci (Got-2 and Dip-A). Based on 3,111,598 allele generations: (1) the average mutation rate to new mobility variants with normal function was estimated to be 1.28 x 10-6, and (2) the average mutation rate to null alleles was estimated to be 3.86 x 10-6. A qualitative analysis of the nulls provided evidence that most of the mutants recovered are due to base substitutions. No apparent correlation was observed between structural gene size and mutation rate.

Genetic variation and progressive evolution.

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.

Rate of spontaneous mutation at human loci encoding protein structure.

Abstract: The techniques of electrophoresis were used in a search for evidence of mutation affecting protein structure, the indicators being hemoglobin and a set of serum proteins and erythrocyte enzymes. Among 94,796 locus tests on Amerindians from Central and South America, there was no evidence for mutation. Among 105,649 locus tests on newborn infants in Ann Arbor, Michigan, there was also no evidence for mutation. We have previously failed to encounter any mutations in a series of 208,196 locus tests involving Japanese children [Neel, J. V., Satoh, C., Hamilton, H. B., Otake, M., Goriki, K., Kageoka, T., Fugita, M., Neriishi, S & Asakawa,J. (1980) Proc. Natl. Acad. Sci. USA 77, 4221-4225], and H. Harris, D. A. Hopkinson, and E. B. Robson [(1974) Ann. Hum. Genet. 37, 237-253] found no mutations in 113,478 locus tests on inhabitants of the United Kingdom. This failure to demonstrate any mutations of this type in a total of 522,119 locus tests excludes, at the 95% level of probability, a mutation rate greater than 0.6 X 10(-5)/locus per generation in this combination of populations.

Haplodiploid sex ratios and the mutation rate

Abstract: Deviations from a 1:1 sex ratio in species with haplodiploid genetics are well known and sociobiologists have produced various explanations1–8, all of which ignore the effect of mutations on haploid viability. Lethal recessive mutations can significantly increase male (haploid) mortality and their effect should be estimated to provide the appropriate null hypothesis with which to compare observed sex ratios before considering any more complex, sociobiological hypothesis. Prospective maternal care4 and local mate competition1,2 will also affect sex ratio, but increased haploid mortality due to mutation rate is the only effect common to all haplodiploid species. Using emergence data for some parasitoid species, the rate of mutation to lethal recessives is estimated to be about 0.035 per genome per generation giving a differential haploid mortality of 10%.

No sex difference in mutations rates of Duchenne muscular dystrophy.

Abstract: Segregation analysis was performed to evaluate possible differences in mutation rates in man. It was based on 514 males with Duchenne type muscular dystrophy (DMD) from five of nineteen hospitals for muscular disease in Japan. The estimated proportion of sporadic cases (new mutations) was 0.29 +/- 0.046, which is in excellent agreement with the expected 0.333 if there is no sex difference in mutation rates. The rate of mutation was estimated to be 6.3 X 10(-5) per generation. The incidence and prevalence rates among males were estimated to be 217 X 10(-6) and 49.9 X 10(-6), respectively.

Mutational process and microevolution

Abstract: Long term observations of the gene pool of the same and geographically separated populations of Drosophila melanogaster forced us to return to the old idea of De Vries about the existence of mutation periods and fluctuations in the mutation rate with time. A 3- to 5-fold increase of the total mutation rate was estimated by the frequency of lethals, and outbursts of mutability of some X-linked loci were registered. In 1973 the mutation frequency of the singed bristle locus increased in many populations. An outburst of mutability up to 10-2 – 10-3 was accompanied by the unstable conditions of newly arisen mutations, and their ability to produce with a great frequency various allelic variants in the progeny. Two main types of instability have been established: (A) Changes occur in accordance with the ‘all or nothing’ principle: from an extreme mutant expression to a phenotypically normal one, and vice versa; (B.) Mutants with intermediate phenotypic expression give rise to a fan of allelic derivatives in progeny. Mutations occur long before meiosis and proceed at different rates in sexual and somatic cells. The whole body of indirect evidence indicates that the instability is the result of the incorporation of insertion mutations and frequent changes of orientation of some alien segments of DNA. When evaluating the mutation process in natural populations one should take into account that: It is suggested that some infectious agents may be acting synchronously in isolated populations as selective factor and as factor inducing unstable states of genetic loci.

Determination of the expression time and the dose-response relationship for mutations at the HGPRT (hypoxanthine-guanine-phosphoribosyl transferase) locus induced by X-irradiation in human diploid skin fibroblasts

Abstract: The lenth of the expression time for mutants resistant to 8-azaguanine or 6-thioguanine induced by X-rays was determined in human diploid skin fibrobalsts. The cells were seeded in the selective medium over a period of 14 days after treatment. Direct expression of at least a part of the mutants was observed at day 0, and an increase of the mutant frequency over the entire cultivation period appeared to be due to spontaneous mutation. The dose-response relationship does not appear to deviate from linearity. The mutation rate per R had a mean value of 2.1 × 10−7 which is about twice the value of the mutation rate found in rodent cells for the same locus.

Interaction of an Escherichia coli mutator gene with a deoxyribonucleotide effector.

Abstract: Strains of Escherichia coli carrying mutD5 display very high mutation rates (about 10(4)-fold above wild-type) when grown in rich medium, but relatively low mutation rates (about 10- to 50-fold above wild-type) in minimal medium. Thymidine, deoxycytidine, and deoxyuridine are all capable of stimulating mutation when added to minimal medium. Studies with mutants blocked in various steps of thymidine metabolism implicate a phosphorylated thymidine effector which mediates the mutagenic action of the added deoxyribonucleotides. In addition, an unidentified compound or compounds other than thymidine present in rich medium (L-broth) can also increase the mutation rate.

Estimation of male to female ratio of mutation rates from carrier-detection tests in X-linked disorders.

Abstract: A method is presented for the estimation of the ratio of male to female mutation rates from female carrier-detection test data from pedigrees containing an isolated male manifesting an X-linked necessive disorder. Pedigrees of any size and complexity (barring consanguinity) and containing any number of tested females can be utilized. The relative fitness of affected males and carrier females, and the segregation probability of the abnormal gamete in females, can be estimated simultaneously with the ratio of mutation rates in order to test specific hypotheses against given bodies of data. Here this method is applied to families containing isolated individuals affected with Lesch-Nyhan syndrome.

Rapid Estimation of the Number of Sex Alleles in Panmictic Honeybee Populations

Abstract: SummaryA simple formula, based on Kerr's (1967), is proposed for estimating the number of sex alleles in a panmictic honeybee population. Only the mutation rate and the number of colonies need be known. Values are in agreement with those obtained by other methods, especially with a mutation rate of 10−5. The only exception is the population on Kangaroo Island, S. Australia (Woyke, 1976), which is not considered to be a panmictic unity.

Genetic identity between populations when mutation rates vary within and across loci

Abstract: A formula is derived for the probability that two genes taken at random from the same locus in two populations isolated at time t ago are of the same allelic type. The model assumed is a neutral one where there are possibly different mutation rates between different alleles. Inequalities are derived for this probability. A particular result is that for a fixed overall mutation rate, the probability is least for the infinite alleles model. Inequalities and approximations are found for Nei's genetic identity at one locus when mutation rates vary, and also for the identity across loci when the overall mutation rates per locus vary. Genetic identity at the molecular level is considered and a probability generating function found for the number of segregating sites between two randomly chosen gametes from two divergent populations, under various models.

The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. Xiv. Effects of the Incomplete Dominance of the IN(2LR)SM1 (Cy) Chromosome on the Estimates of Various Genetic Parameters

Abstract: Recent reports (MUKAI et al. 1974; KATZand CARDELLINO1978; COCKER-HAM and MUEAI 1978) have indicated that the Cy chromosome is not always dominant over its homologous chromosome with respect to viability. Thus,the genetic parameters previously estimated using viabilities determined by the Cy method are biased. In the present paper, the biases of the estimates for the polygenic mutation rate, the degree of dominance and the homozygous load are examined. The results indicate that the biases for the mutation rate and the degree ofdominance are small and that the estimate of the homozygous load relative to the average viability of the population is not biased.

Composite stepwise mutation model under the neutral mutation hypothesis.

Abstract: As an extension of the conventional (“Ohta-Kimura”) stepwise mutation model, a new model is proposed In this model, it is assumed that each charge state (“electromorph”) is represented byK alleles and that a mutation changes an allele either by one step in the charge space or to one of the other members of the identical electromorph It is shown that the net genetic variability within a population is similar to that predicted by the infinite-allele model (“Kimura-Crow” model) rather than to that predicted by the stepwise mutation model, and theK-dependence of genetic variability is rather weak whenK ⩾ 2 and the effective population size is not much greater than the reciprocal of mutation rate The results are compared with the recent observations at the xanthine dehydrogenase locus inDrosophila pseudoobscura

Factors affecting electromorph mutation rates in man: an analysis of data from Australian Aborigines.

Abstract: The constraints of molecular size and structure on the relative magnitudes of electromorph mutation rates as calculated indirectly have been studies using data for Australian Aborigines. The role of sample size in detecting rare electromorphs is important. In addition, subunit size shows a positive and subunit number a negative correlation with mutation rate. The differences in mutation rates were 2--9-fold when calculated for different categories of the data. The importance of physicochemical constraints are discussed.

Genetic effects of space hadrons on bacteriophage under Alpine conditions.

Abstract: A dried film culture of bacteriophage T4Br+ was kept in a lead bioblock for 366 days under Alpine conditions at an altitude of 6100 m above sea level to study the genetic effect of space hadrons. In the gelatin-like film under study we discovered some film plots with markedly reduced bacteriophage survival. In such plots, the mutation frequency exceeded the spontaneous background mutation rate 60–100 times. The spectrum of r mutations as classified into standard groups rI, rII and rIII differed from that found for other model radiation systems such as γ-ray radiation in buffer or nutrient broth, and hadron and HZE particle radiation under space flight conditions. Reversion analysis of 159 rII mutants showed that 54.4% had small and elongated deletions, 23.16% had point mutations, and 22.5% of all the mutants had both small deletion and point mutations.

Dna rearrangements in is2 that form new promoters

Abstract: A system was developed that allowed the selection of mutations which had promoter activity. A variety of different events was observed. A mutation was found that increased the frequency of one particular class of events but not of a second class. This mutation was not in the polA locus.