Mutation Rate In Drosophila Research Articles

Raissa L. Berg's contributions to the study of phenotypic integration, with a professional biographical sketch.

Raissa L. Berg had a remarkable career in many respects and an impact on the study of phenotypic integration that continues to increase over 50 years after the publication of her seminal paper in that area. She was born and lived most of her life in Russia, with most of her research focused on measuring spontaneous mutation rates in Drosophila. She was forced to abandon this work during the height of Lysenko's power in Russia, so she turned temporarily to the study of correlation patterns in plants; ironically, this work has had a more enduring impact than her main body of research. She showed that floral and vegetative traits become decoupled into separate correlation 'pleiades' in plants with specialized pollinators, but floral and vegetative traits remain correlated in plants that have less specialized pollination. Unfortunately, her plant work is often mis-cited as providing evidence for increased correlations among floral traits due to selection by pollinators for functional integration, a point she never made and one that is not supported by her data. Still, many studies of correlation pleiades have been conducted in plants, with the results mostly supporting Berg's hypothesis, although more studies on species with generalized pollination are needed.

Evidence for elevated mutation rates in low-quality genotypes

The deleterious mutation rate plays a key role in a number of important topics in biology, from mating system evolution to human health. Despite this broad significance, the nature and causes of variation in mutation rate are poorly understood, especially in multicellular organisms. We test whether genetic quality, the presence or absence of deleterious alleles, affects the mutation rate in Drosophila melanogaster by using a modified mutation accumulation approach. We find evidence that genotypes constructed to carry deleterious "treatment" alleles on one chromosome during mutation accumulation experience an elevated mutation rate on a different chromosome. Further, this elevation is correlated with the effect of the treatment alleles on phenotypic condition, measured as body mass. Treatment alleles that reduce mass by 10% cause a doubling in the rate of mutational decline. Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.

Erratum: Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila

Nature 445, 82–85 (2007) In this Letter, David Houle was omitted from the author list. David Houle was responsible for producing the Florida mutation accumulation lines that were analysed in the experiment.

Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila

Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation (U) appears in theories of nucleotide divergence and polymorphism, the evolution of sex and recombination, and the evolutionary consequences of inbreeding. However, estimates of U based on changes in allozymes or DNA sequences and fitness traits are discordant. Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography. From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u among the three mutation-accumulation-line genotypes. By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila, we estimate that U is 1.2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction.

Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans.

Theory concerning the evolution of sex and recombination and mutation load relies on information on rates and distributions of effects of deleterious mutations. Direct information on the genomic mutation rate in Drosophila implies that an accumulation of mildly deleterious mutations reduces viability of populations by at least 1% per generation. We carried out an experiment to measure the deleterious mutation rate in Caenorhabditis elegans, in which independent sublines were maintained with one hermaphrodite parent per generation, conditions that minimize the opportunity for natural selection and lead to random fixation of deleterious mutations. After 60 generations of mutation accumulation, negligible changes in mean reproductive output and lifespan occurred, but the genetic variance increased at rates typical for life history traits in other species. The estimated deleterious mutation rate per haploid genome for fitness, U, was 0.0026, a figure two orders of magnitude smaller than previously measured for viability in Drosophila.

The distribution of mutation effects on viability in Drosophila melanogaster.

Parameters of continuous distributions of effects and rates of spontaneous mutation for relative viability in Drosophila are estimated by maximum likelihood from data of two published experiments on accumulation of mutations on protected second chromosomes. A model of equal mutant effects gives a poor fit to the data of the two experiments; higher likelihoods are obtained with leptokurtic distributions or for models in which there is more than one class of mutation effect. Minimum estimates of mutation rates (events per generation) at polygenes affecting viability on chromosome 2 are 0.14 and 0.068, but estimates are strongly confounded with other parameters in the model. Separate information on rates of molecular divergence between Drosophila species and from rates of movement of transposable elements is used to infer the overall genomic mutation rate in Drosophila, and the viability data are analyzed with mutation rate as a known parameter. If, for example, a mutation rate for chromosome 2 of 0.4 is assumed, maximum likelihood estimates of mean mutant effect on relative viability are 0.4% and 1%, but the majority of mutations have very much smaller effects than these values as distributions are highly leptokurtic. The methodology is applied to estimate viability effects of single P element insertional mutations. The mean effect per insertion is found to be higher, and their distribution is found to be less leptokurtic than for spontaneous mutations. The equilibrium genetic variance of viability predicted by a mutation-selection balance model with parameters estimated from the mutation accumulation experiments is similar to laboratory estimates of genetic variance of viability from natural populations of Drosophila.

Vitamin C-mediated minimisation of Rogor-induced genotoxicity

The genotoxic effect of Rogor (an organophosphorous pesticide) at concentrations used in agriculture was studied in terms of mitotic index in onion root-tip cells, chromosome abnormalities and meiotic index in mice and lastly, lethal mutation rate in Drosophila. It was observed that the pesticide could (i) cause mitotic as well as meiotic inhibition, (ii) increase the clastogenicity rate and (iii) induce lethal mutations. The modificatory role, if any, of l-ascorbic acid (vitamin C) was studied after administering the vitamin concurrently with the pesticide. It was observed that the cytogenetic toxicity of Rogor can be appreciably minimised by vitamin C. The possible mode of antigenotoxic action of vitamin C was discussed.

Lethal mutation rate in Drosophila exposed to LSD-25 by injection and ingestion.

ALTHOUGH attempts have been made to assess the effect of D-lysergic acid diethylamide (LSD-25) on human chromosomes, it has yet to be unequivocally determined when and in what circumstances this chemical is mutagenic. From karyotype analyses of individuals who have ingested LSD-25 some investigators have concluded that it is not mutagenic1,2 while others have reported a high incidence of chromosome aberrations among such individuals3,4 as well as among human leucocytes treated in vivo3. Because of its long standing utility in the detection of induced mutations Drosophila seems to be a likely organism with which to investigate this problem further. Reports have recently appeared which indicate that while LSD-25 is not apparently mutagenic when injected directly in D. melanogaster males in amounts as great as 500 µg/ml. (ref. 5) it is capable of producing X-linked recessive lethal mutations when doses some twenty times larger are used6.

Mutation rates at a new set of specific loci in the mouse.

Previous measurements of specific locus mutation rates in mice had all involved the seven loci,a, b, c, d, p, sandse. An experiment was performed with the same mouse stock (C3H × 101) and the same radiation dose (600 rad) to spermatogonia as had been used previously, but employing a new group of six loci,a, bp, fz, In, paandpe. The observed mutation rate, 5·0 × 10−8per locus per rad, was significantly lower than that for the original seven loci, but was three to four times higher than the corresponding mutation rate inDrosophila melanogaster.

THE EFFECTS OF X RAYS ON INSEMINATION AND SPERM RETENTION IN DROSOPHILA.

The effect of x rays on insemination success and retention of sperm during storage in inseminated females was studied by direct microscopic estimates of the relative fullness of excised ventral receptacles in female Drosophila melanogaster dissected at intervals following mating. Males were treated at 12 x- ray dose levels ranging from 500 to 75000 r and mated for 24 hours to untreated, virgin females. The insemination success in groups of females dissected immediately after the mating period was significantly lower in treated groups than in the controls at all doses of 4000 r or more. The reduction in insemination was proportional to -0.0066 times the dose in kiloroentgens at doses to 40 kr, and was even more extreme at doses of 60 and 75 kr. Males were treated with 4000, 25000, or 50000 r of x rays and mated for 24 hours to virgin untreated females. The insemination success in females dissected immediately after the mating period was lower in each treated group, and the retention of sperm after 7 and 14 days of storage in the females was drastically reduced in the 25000 and 50000 r groups. Inseminated females were treated at eight x ray dose levels ranging frommore » 5000 r to 50000 r, and dissected at times ranging from 2 hours to 17 days after irradiation. Reductions in the success of the sperm retention were first noted 24 hours after irradiation at the highest dose levels, and became evident even at lower doses within the 17-day storage period. It was concluded that some aspect of sperm behavior, possibly motility, is affected by x rays at doses within the range commonly employed in genetic studies. This finding is significant for the analysis of induced mutation rates in Drosophila. (auth)« less

Heat as an Agent producing High Frequency of Mutations and Unstable Genes in Escherichia coli

MILD heating (up to 36° C.) is known to produce a small increase of the spontaneous mutation-rates in Drosophila and in bacteria. We have found that using special conditions it is possible to have mesophilic non-sporogenic bacteria (Escherichia coli) survive relatively high temperatures (60° C.) ; this sublethal treatment produces a high frequency of mutations and unstable genes.

Approximate Confidence Intervals for Specific Locus Mutation Rates

A method is proposed for constructing approximate confidence intervals for specific locus mutation rates. The assumptions on which the method is based have been tested by an analysis of published data on mutation rates, and the results of the analysis indicate that the assumptions are conservative. This implies that if the method is in error, it will lead to confidence intervals which are too large rather than too small. The method is applied to data from radiation experiments with Drosophila and mice, and the results support a conclusion made by Russell (1951, 1956) that the spermatogonia mutation rate in mice is higher than the spermatogonia mutation rate in Drosophila.

Comparison of X-Ray-Induced Mutation Rates in Drosophila and Mice

Previous articleNext article No AccessComparison of X-Ray-Induced Mutation Rates in Drosophila and MiceW. L. RussellW. L. Russell Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The American Naturalist Volume 90, Number 850Jan. - Feb., 1956Supplement: Comparison of X-Ray-Induced Mutation Rates in Drosophila and Mice Published for The American Society of Naturalists Article DOIhttps://doi.org/10.1086/281910 Views: 8Total views on this site Citations: 28Citations are reported from Crossref PDF download Crossref reports the following articles citing this article:Edward J. Calabrese, Paul B. 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Radiation Induced Mutation Rates in Drosophila and Mice

This paper discusses the comparison of radiation-induced mutation rates in Drosophila and mice considering principally the data of Russell, Alexander and the author. It is argued that the comparison should be made on the basis of F1 results using only autosomal loci, for four reasons: (1) differences in viability and fertility of the presumptive F1 mutants in the two forms; (2) difference in time of separation of germ and somatic cell lines in the two forms; (3) the lack of knowledge on the comparative decrease in proportion of recovered mutations when testing sperm radiated at different developmental ages in the two forms; and (4) apparent differences in mutation rates of X-chromosomal and autosomal loci in Drosophila. Considering also the extreme non-randomness of the mutation rates of the few autosomal loci so far studied it is concluded that for the present the radiation-induced mutation rate per r per locus appears to be similar in flies and mice.

CHEMICAL MUTAGENESIS

CHEMICAL MUTAGENESIS

Spontaneous Mutation Rate in Drosophila

The frequency of spontaneously occurring lethal mutations in the X-chromosome of the Sw-b stock of D. melanogaster was found to be higher among spermatozoa of previously unmated males 16 to 17 days, and 32 to 33 days after emergence than among 1- to 2-day old males (Table 1).