[Studies on closed mines from the stand-point of social medicine. Report I. Health hazards among workers and residents at Toroku mine (author's transl)].
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Biomedical subjects
Publications and source records attributed to T Ohta.
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A formula for the distribution of allelic frequencies in a finite population is derived assuming stepwise production of multiple alleles. Monte Carlo experiments were performed to check the validity of the formula, and excellent agreement was obtained between theoretical distribution and experimental results. The formula should be useful for analyzing genetic variability in natural populations that can be detected by electrophoretic methods.
A new deterministic formulation is derived of the equilibrium between mutation and natural selection, which takes into account(a) the possibility of many allelic mutation states, (b) selection coefficients of the order of magnitude of the mutation rate and (c) the possibility of further mutation of already mutant alleles. The frequencies of classes of alleles 0, 1, 2, n mutant steps removed from the type allele are shown to form a Poisson distribution, with a mean and variance of the mutation rate divided by the coefficient of selection against each incremental mutational step.--This formulation is interpreted in terms of the expected frequencies of electromorphs, defined as classes of alleles characterized by common electrophoretic mobilities of their protein products. Electromorph frequencies are predicted to form stable unimodal distributions of relatively few phenotypic classes. Common electromorph frequencies found throughout the ranges of species with large population sizes are interpreted as being a uniquely electrophoretic phenomenon; band patterns on starch and acrylamide gels are phenotypes, not genotypes. It is predicted that individual electromorphs are highly heterogenous with regard to amino acid sequence.
The incidence of drowsings as a cause of near traffic accidents was studied on the basis of daily recordings or near accidental events by 288 locomotive drivers during a rotation period of 2-3 weeks. Of 198 near accidents reported during 2,290 trips, 34 cases, or 1,5 cases per 100 trips, were operation missess involving drowsing or strong drowsiness. Improper operation due to drowsing occurred at a certain rate for any group of drivers, irrespective of the type of train, running sections, weather, and other operative conditions such as train delays, whereas 117 cases of danger caused by unforeseen obstacles on the track were related to site characteristics, and 47 cases of other disorders were frequent in unusual operative conditions such as arrival-departure, poor signal display, wrong instructions, or equipment failure. Thus continued driving under ordinary track conditions at a more or less constant speed was likely to induce drowsiness under the dominant influences of fatigue and time of the day; 79% of such cases occurred between midnight and 6 a.m. Most drowsings on the second night appeared during the first 2-4 hr of duty. Effects of monotony and insufficient rest were discussed in relation to recurrent fluctuation in vigilance.
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THE FOLLOWING FIVE PRINCIPLES WERE DEDUCED FROM THE ACCUMULATED EVIDENCE ON MOLECULAR EVOLUTION AND THEORETICAL CONSIDERATIONS OF THE POPULATION DYNAMICS OF MUTANT SUBSTITUTIONS: (i) for each protein, the rate of evolution in terms of amino acid substitutions is approximately constant/site per year for various lines, as long as the function and tertiary structure of the molecule remain essentially unaltered. (ii) Functionally less important molecules or parts of a molecule evolve (in terms of mutant substitutions) faster than more important ones. (iii) Those mutant substitutions that disrupt less the existing structure and function of a molecule (conservative substitutions) occur more frequently in evolution than more disruptive ones. (iv) Gene duplication must always precede the emergence of a gene having a new function. (v) Selective elimination of definitely deleterious mutants and random fixation of selectively neutral or very slightly deleterious mutants occur far more frequently in evolution than positive Darwinian selection of definitely advantageous mutants.
A mathematical theory was developed, based on diffusion models, that enables us to compute the probability of a rare mutant allele eventually spreading through a population when the population size changes with time. In particular, we elaborated the case in which the mutant allele has a definite selective advantage and the population expands following the logistic law. In this case, the probability of ultimate fixation of a single mutant is given by u = 2s(Z/N), where s is the selective advantage and Z/N is a factor by which the probability of fixation is modified through population expansion. Analytical expression was obtained for Z/N, and the validity of the formula for u was checked by Monte Carlo experiments.
Using a new model of isoalleles, extensive Monte Carlo experiments were performed to examine the pattern of allelic distribution in a finite population. In this model it was assumed that the set of allelic states is represented by discrete points on a one-dimensional lattice and that change of state by mutation occurs in such a way that an allele moves either one step in the positive direction or one step in the negative direction on the lattice. Such a model was considered to be appropriate for estimating theoretically the number of electrophoretically detectable alleles within a population. The evenness of allelic distribution was measured by the ratio of the effective to the actual number of alleles (n(e)/n(a)). The results of the Monte Carlo experiments have shown that this ratio is generally larger under the new model of isoalleles than under the conventional Kimura-Crow model of neutral isoalleles. In other words, the distribution of allelic frequencies within a population is expected to be more uniform in the new model. By comparing the Monte Carlo results with actual observations, it was concluded that the observed deviation from what is predicted under the new model with selective neutrality is not in the direction of conforming to the overdominance hypothesis but is, in fact, in the opposite direction.
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Formulae for the mean and the mean square age of a neutral allele which is segregating with frequency x in a population of effective size N(e) have been obtained using the diffusion equation method, for the case of 4N(e)v<1 where v is the mutation rate. It has been shown that the average ages of neutral alleles, even if their frequencies are relatively low, are quite old. For example, a neutral mutant whose current frequency is 10% has the expected age roughly equal to the effective population size N(e) and the standard deviation 1.4N(e) (in generations), assuming that this mutant has increased by random drift from a very low frequency. Also, formulae for the mean "first arrival time" of a neutral mutant to a certain frequency x have been presented. In addition, a new, approximate method has been developed which enables us to obtain the condition under which frequencies of "rare" polymorphic alleles among local populations are expected to be uniform if the alleles are selectively neutral.-It was concluded that exchange of only a few individuals on the average between adjacent colonies per generation is enough to bring about such a uniformity of frequencies.
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