Mutations in the mitochondrial genome have been implicated in numerous human genetic disorders and offer important data for phylogenetic, forensic, and population genetic studies. Using a long-term ...series of Caenorhabditis elegans mutation accumulation lines, we performed a wide-scale screen for mutations in the mitochondrial genome that revealed a mutation rate that is two orders of magnitude higher than previous indirect estimates, a highly biased mutational spectrum, multiple mutations affecting coding function, as well as mutational hotspots at homopolymeric nucleotide stretches.
Spontaneous mutation to mildly deleterious alleles has emerged as a potentially unifying component of a variety of observations in evolutionary genetics and molecular evolution. However, the ...biological significance of hypotheses based on mildly deleterious mutation depends critically on the rate at which new mutations arise and on their average effects. A long-term mutation-accumulation experiment with replicate lines of the nematode Caenorhabditis elegans maintained by single-progeny descent indicates that recurrent spontaneous mutation causes approximately 0.1% decline in fitness per generation, which is about an order of magnitude less than that suggested by previous studies with Drosophila. Two rather different approaches, Bateman-Mukai and maximum likelihood, suggest that this observation, along with the observed rate of increase in the variance of fitness among lines, is consistent with a genomic deleterious mutation rate for fitness of approximately 0.03 per generation and with an average homozygous effect of approximately 12%. The distribution of mutational effects for fitness appears to have a relatively low coefficient of variation, being no more extreme than expected for a negative exponential, and for one composite fitness measure (total progeny production) approaches constancy of effects. These results are derived from assays in a benign environment. At stressful temperatures, estimates of the genomic deleterious mutation rate (for genes expressed at such temperatures) is sixfold lower, whereas those for the average homozygous effect is approximately eightfold higher. Our results are reasonably compatible with existing estimates for flies, when one considers the differences between these species in the number of germ-line cell divisions per generation and the magnitude of transposable element activity. Corresponding Editor: A. Caballero
Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of approximately 50 generations. Periodic assays of these lines and comparison to a frozen ...control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability approximately 0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.
. Spontaneous mutation to mildly deleterious alleles has emerged as a potentially unifying component of a variety of observations in evolutionary genetics and molecular evolution. However, the ...biological significance of hypotheses based on mildly deleterious mutation depends critically on the rate at which new mutations arise and on their average effects. A long‐term mutation‐accumulation experiment with replicate lines of the nematode Caenorhabditis elegans maintained by single‐progeny descent indicates that recurrent spontaneous mutation causes approximately 0.1% decline in fitness per generation, which is about an order of magnitude less than that suggested by previous studies with Drosophila. Two rather different approaches, Bateman‐Mukai and maximum likelihood, suggest that this observation, along with the observed rate of increase in the variance of fitness among lines, is consistent with a genomic deleterious mutation rate for fitness of approximately 0.03 per generation and with an average homozygous effect of approximately 12%. The distribution of mutational effects for fitness appears to have a relatively low coefficient of variation, being no more extreme than expected for a negative exponential, and for one composite fitness measure (total progeny production) approaches constancy of effects. These results are derived from assays in a benign environment. At stressful temperatures, estimates of the genomic deleterious mutation rate (for genes expressed at such temperatures) is sixfold lower, whereas those for the average homozygous effect is approximately eightfold higher. Our results are reasonably compatible with existing estimates for flies, when one considers the differences between these species in the number of germ‐line cell divisions per generation and the magnitude of transposable element activity.
We measured the impact of new mutations on genetic variation for body size in two independent sets of C. elegans spontaneous mutation-accumulation (MA) lines, derived from the N2 strain, that had ...been maintained by selfing for 60 or 152 generations. The two sets of lines gave broadly consistent results. The change of among-line genetic variation between cryopreserved controls and the MA lines implied that broad sense heritability increased by 0.4% per generation. Overall, MA reduced mean body size by approximately 0.1% per generation. The genome-wide rate for mutations with detectable effects on size was estimated to be approximately 0.0025 per haploid genome per generation, and their mean effects were approximately 20%. The proportion of mutations that increase body size was estimated by maximum likelihood to be no more than 20%, suggesting that the amount of mutational variation available for selection for increased size could be quite small. This hypothesis was supported by an artificial selection experiment on adult body size, started from a single highly inbred N2 individual. We observed a strongly asymmetrical response to selection of a magnitude consistent with the input of mutational variance observed in the MA experiment.
Mutations in the C. elegans gene
lin-44 lead to reversals in the polarity of certain asymmetric cell divisions. We have discovered that
lin-44 is a member of the
Wnt family of genes, which encode ...secretory glycoproteins implicated in intercellular signaling. Both in situ hybridization experiments using
lin-44 transcripts and experiments using reporter constructs designed to mimic patterns of
lin-44 expression indicate that
lin-44 is expressed in hypodermal cells at the tip of the tail and posterior to the cells with polarities affected by
lin-44 mutations. Our mosaic analysis indicates that
lin-44 acts cell nonautonomously. We propose that LIN-44 protein is secreted by tail hypodermal cells and affects the polarity of asymmetric cell divisions that occur more anteriorly in the tail.
Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of ...extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.
HintergrundZiel der durchgeführten Studie war es, festzustellen, ob die manualmedizinische Behandlung der Kopfgelenke bei Tonusasymmetrie/KISS-Kindern eine Veränderung der Gesichtsasymmetrie und ...dementsprechend der Fehlposition und Funktion der Schädelknochen auslösen kann.Material und MethodenEs wurden 30 Säuglinge mit Funktionsstörungen der Kopfgelenke und einer typischen Gesichts-, Schädel- und Haltungsasymmetrie in der Praxis manualtherapeutisch und osteopathisch untersucht.ErgebnisseDie Gesichtsasymmetrie ist bei 20 Kindern viel besser bzw. besser geworden, bei 10 Kindern blieb sie unverändert. Die Augenasymmetrie wurde bei 23 Kindern besser, und bei 7 Kindern blieb sie unverändert. Die Schädelasymmetrie wurde bei 21 Kindern besser, und bei 9 blieb sie unverändert.SchlussfolgerungMit der Beseitigung der sekundären Anpassungsreaktionen des kraniosakralen Systems in Form einer Torsionsläsion der SBS lässt sich teilweise die Wirkung der manuellen Therapie bei Säuglingen verstehen und erklären.
The ATLAS Inner Detector consists of three sub-systems, the Pixel Detector at the innermost radius, the Semi-Conductor Tracker at intermediate radii, and the Transition Radiation Tracker (TRT) at the ...outermost radius in front of the electromagnetic calorimeter. The TRT provides a combination of continuous tracking with many projective measurements based on individual drift-tubes (or straws) and of electron identification based on radiator fibres or foils interleaved between the straws themselves. This paper describes the current status of design and construction of the various components of the TRT: the assembly of the barrel modules has recently been completed, that of the end-cap wheels is well underway, and the on-detector front-end electronics is in production. The detector modules and front-end electronics boards will be integrated together over the next year, the barrel and end-cap TRT parts will be assembled and tested with their SCT counterparts during 2005 and installation and commissioning in the ATLAS pit will take place at the end of 2005 and the beginning of 2006.
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