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Biomedical subjects

J F Crow

Publications and source records attributed to J F Crow.

At least 91 records · Page 5Linked to original sources
PubMed1981

The mutation component of genetic damage.

The mutation component, M, is a measure of the proportion of the impact of a genetic condition that is attributable to recurrent mutation. For a trait maintained by balance between mutation and directional selection, M is approximately the broad-sense heritability; for a measured character where the mean and optimum coincide, M is about half the heritability. If the narrow-sense heritability is high, the impact changes relatively rapidly with a change in mutation rate. If the narrow-sense heritability is low, M cannot be predicted, but the change in impact following a change in mutation rate, if any, is very slow.

Genetics, Medical↗
PubMed1979

Efficiency of truncation selection.

Truncation selection is known to be the most efficient form of directional selection. When this is modified so that the fitness increases linearly over a range of one or two standard deviations of the value of the selected character, the efficiency is reduced, but not greatly. When truncation selection is compared to a system in which fitness is strictly proportional to the character value, the relative efficiency of truncation selection is given by f(c)/sigma, in which f(c) is the ordinate of the frequency distribution at the truncation point and sigma is the standard deviation of the character. It is shown, for mutations affecting viability in Drosophila, that truncation selection or reasonable departures therefrom can reduce the mutation load greatly. This may be one way to reconcile the very high mutation rate of such genes with a small mutation load. The truncation model with directional selection is appropriate for this situation because of the approximate additivity of these mutations. On the other hand, it is doubtful that this simple model can be applied to all genes affecting fitness, for which there are intermediate optima and antagonistic selection among components with negative correlations. Whether nature ranks and truncates, or approximates this behavior, is an empirical question, yet to be answered.

Journal Article↗
PubMed1979

Development of departmental promotion guidelines.

In making optimum use of its faculty, a medical school department should ensure that each faculty member has a clear understanding of what is expected of him and what will be evaluated when he is considered for reappointment or promotion. A set of departmental promotion guidelines which are available to all faculty can serve both these ends. In addition to defining the nature of the work which will be evaluated and stressing that performance quality is important, such guidelines should make explicit the various ways in which the work will benefit the department, the medical school, and the discipline. The guidelines can be used at the time of promotion, but they should also contribute to an ongoing evaluation of faculty work by the administration and by the faculty themselves.

Achievement↗
PubMed1979

Gene frequency and fitness change in an age-structured population.

Fisher's system of reproductive value weighting, whereby each age group is assigned a weight purported to measure its contribution to the ancestry of future generations, was suggested by him as a way of ironing out irregularities in the change of population numbers when the age structure is not in equilibrium. This has been extended to Mendelian populations for two models. In Model I, the reproductive value of each genotype is computed from a table of age-specific survival and reproduction rates, and the genic values are computed by averaging these genotypic values. The total reproductive value of an allele and of the population always increase at a rate equal to the reproductive value-weighted average fitness regardless of age structure. This has the disadvantage that the total reproductive value is not equal to the census numbers, when age-stability has been reached. In Model II, this difficulty is surmounted, but the formula is no longer exact. The reproductive value of an allele for a specific age x is measured from the average death and reproductive rates of individuals of age x carrying that allele. An expression is given for the rate of change of reproductive value of an allele or of the population. In many circumstances this changes nearly uniformly, regardless of irregularities of age structure, and goes over to the census numbers as age stability is approached. The special difficulties in populations with separate sexes are discussed and a formula for rate of change of mean reproductive value, analogous to Fisher's Fundamental Theorem of Natural Selection, is given.

Age Factors↗
PubMed1979

Minor viability mutants in Drosophila.

Drosophila experiments have demonstrated that spontaneous mutants causing minor decreases in viability occur much more often than those causing drastic effects. They also have a much greater relative effect in heterozygotes, enough that the absolute heterozygous viability decrease is roughly the same for mild as for lethal mutants. On the other hand, with EMS treatment and especially with radiation, the mild mutants are less frequent relative to lethals.--I suggest that the failure to detect heterozygous effects on fitness components from multi-generation radiation experiments on mice due to the relative infrequency of mild effects and the relatively small heterozygous effect of drastic mutants. Chemicals that produce effects more like spontaneous mutations might produce quite different results in such experiments.

Animals↗
PubMed1978

Effect of overall phenotypic selection on genetic change at individual loci.

The selective advantage of an allele Gi (relative to the mean of alleles at this locus) is given by (formula: see text) in which Ai is the average excess of the allele on the character, X; W(X) is the fitness function; F(X) is the frequency function; W is the mean fitness; and the prime denotes differentiation. With truncation selection si = AaF(C)/w in which F(C) is the ordinate at the culling level and w is the proportion saved; this does not depend on any assumption about the distribution of F(X). If the character is normally distributed, si = AiI/sigma2, in which I is the selection differential and sigma2 is the variance of the character distribution. Finally, if the logarithm of the fitness is proportional to the squared deviation from the optimum and the character is distributed normally, si = AiK(Xop--m), in which Xop is the optimum value of the character, m is the mean value, and K is a constant determined by the variances of the fitness function and the frequency function. Truncation is the most efficient form of directional selection in the sense of producing the maximum gene frequency change for a given effect of the gene on the character, but fitness functions can depart considerably from sharp truncation without greatly reducing the efficiency.

Gene Frequency↗
PubMed1978

Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster.

The heterozygous effects on fitness of second chromosomes carrying mutants induced with different doses of EMS were ascertained by monitoring changes in chromosome frequencies over time. These changes were observed in populations in which the treated chromosomes, as well as untreated competitors, remained heterozygous in males generation after generation. This situation was achieved by using a translocation which links the second chromosome to the X chromosome; however, only untranslocated second chromosomes were mutagenized. Chromosomes were classified according to their effects on viability in homozygous condition. A preliminary homozygosis identified completely lethal chromosomes; secondary tests distinguished between drastic (viability index < 0.1) and nondrastic chromosomes. Chromosomes that were nondrastic after treatment were found to reduce the fitness of their heterozygous carriers by 3-5%. The data show that flies homozygous for these chromosomes were about 2.7% less viable per treatment with 1 mm EMS than flies homozygous for untreated chromosomes. By comparing the fitness-depressing effects of nondrastic EMS-induced mutants in heterozygous condition with the corresponding viability-depressing effects measured by Temin, it is apparent that the total fitness effects are several times larger than the viability effects alone. Completely lethal chromosomes derived from the most heavily treated material reduced fitness by 11% in heterozygous condition; approximately half of this reduction was due to the lethal mutations themselves.

Animals↗
PubMed1976

The theory of neutral and weakly selected genes.

The controversy over whether a major fraction of evolutionary allele substitutions and protein polymorphisms in natural populations is due to random drift of neutral mutations remains unresolved; but the discussion has led to extensions of population genetic theory, particularly in stochastic models. The work of Maruyama in seeking quantities that are not strongly dependent on assumptions about population structure is particularly discussed. Under some circumstances, and perhaps quite generally, the probability of eventual fixation of a mutant gene, the total number of heterozygotes in which the gene is involved before its fixation or less, and the total number of heterozygotes during the time the gene has a specified frequency in the entire population have this desirable property. Whether there are many mutants that are so nearly neutral as to be unaffected by selective forces or not, it is clear that there are many loci at which selection is very weak and some of the evolutionary consequences of this are discussed briefly.

Amino Acid Sequence↗
PubMed1975

Heterozygous effects of x-ray induced mutations on viability of Drosophila melanogaster.

Drosophila second chromosomes that had received 1000 R of X-irradiation mainly in the mature sperm stage were tested for heterozygous effects on viability. When the genetic background was heterozygous the viability was reduced by about 1.5 percent; in a nearly homozygous background the viability was enhanced by about the same amount. In a partially inbred background the results were intermediate. The results are therefore in agreement with earlier experiments of Wallace and Mukai.

Animals↗
PubMed1974

The direction of linkage disequilibrium.

The previous paper (Langley, Tobari and Kojima 1974) reports that the directional linkage disequilibria, D(omega) = P(AB)P(ab)-P(Ab)P(aB), tend to be negative for data between allozymes and linked to inversions. A and B stand for the two alleles with the greatest frequency in the population. In this paper we show that linkage disequilibrium in this direction is produced at equilibrium when double homozygotes have fitnesses that are a constant fraction of the product of the two component single homozygote fitnesses, a pattern that is frequently observed in experimental data.

Alleles↗
PubMed1974

The genetic variance for viability and its components in a local population of Drosophila melanogaster.

Two hundred and ninety second chromosomes extracted from a natural population of Drosophila melanogaster were analyzed to estimate the genetic variance of viability and its components by means of a partial diallel cross (Design II of Comstock and Robinson 1952). The additive and dominance variances are estimated to be 0.009 and 0.0012. Using the dominance variance and the inbreeding depression, the effective number of overdominant loci contributing to the variance in viability is estimated to be very small, a dozen or less. Either the actual number of loci is small, or the distribution of viabilities is strongly skewed with a large majority of very weakly selected loci. The additive variance in viability appears to be too large to be accounted for by recurrent harmful mutants or by overdominant loci at equilibrium with various genetic parameters estimated independently. The excess might be due to frequency-dependent selection, to negative correlations between viability and fertility, or possibly to the presence of a mutator. The selection for viability and fertility, or possibly to the presence of a mutator. The selection for viability at the average polymorphic locus must be very slight, of the order of 10(-3) or less.

Adaptation, Biological↗