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J F Crow

Publications and source records attributed to J F Crow.

At least 37 records · Page 2Linked to original sources
PubMed1997

The high spontaneous mutation rate: is it a health risk?

The human mutation rate for base substitutions is much higher in males than in females and increases with paternal age. This effect is mainly, if not entirely, due to the large number of cell divisions in the male germ line. The mutation-rate increase is considerably greater than expected if the mutation rate were simply proportional to the number of cell divisions. In contrast, those mutations that are small deletions or rearrangements do not show the paternal age effect. The observed increase with the age of the father in the incidence of children with different dominant mutations is variable, presumably the result of different mixtures of base substitutions and deletions. In Drosophila, the rate of mutations causing minor deleterious effects is estimated to be about one new mutation per zygote. Because of a larger number of genes and a much larger amount of DNA, the human rate is presumably higher. Recently, the Drosophila data have been reanalyzed and the mutation-rate estimate questioned, but I believe that the totality of evidence supports the original conclusion. The most reasonable way in which a species can cope with a high mutation rate is by quasi-truncation selection, whereby a number of mutant genes are eliminated by one "genetic death."

Animals↗
PubMed1995

Spontaneous mutation as a risk factor.

From various estimates of the mutation rate per nucleotide per generation, centering around 1-2 x 10(-8) and the number of nucleotide pairs, 3 x 10(9) per genome, the number of new mutations in a human zygote is very large, in the order of 100. The mutation rate is an order of magnitude higher in males than females, due presumably to the greater number of cell divisions in the male germ line, and increases more than linearly with paternal age. It is likely that a large fraction of these mutations are in unimportant 'junk' DNA, but if even 2% of the mutations are selected, this means two new deleterious mutations per generation. It is suggested that quasi-truncation selection is the most likely way in which this large number of mutations can be eliminated from the population without an excessive burden of reduced viability and fertility.

Age Factors↗
PubMed1994

Advantages of sexual reproduction.

Despite the obvious efficiencies of many forms of asexual reproduction, sexual reproduction abounds. Asexual species, for the most part, are relatively short-lived offshoots of sexual ancestors. From the nineteenth century, it has been recognized that, since there is no obvious advantage to the individuals involved, the advantages of sexual reproduction must be evolutionary. Furthermore, the advantage must be substantial; for example, producing males entails a two-fold cost, compared to dispensing with them and reproducing by parthenogenetic females. There are a large number of plausible hypotheses. To me the most convincing of these are two. The first hypothesis, and the oldest, is that sexual reproduction offers the opportunity to produce recombinant types that can make the population better able to keep up with changes in the environment. Although the subject of a great deal of work, and despite its great plausibility, the hypothesis has been very difficult to test by critical observations or experiments. Second, species with recombination can bunch harmful mutations together and eliminate several in a single "genetic death." Asexual species, can eliminate them only in the same genotype in which they occurred. If the rate of occurrence of deleterious mutations is one or more per zygote, some mechanism for eliminating them efficiently must exist. A test of this mutation load hypothesis for sexual reproduction, then, is to find whether deleterious mutation rates in general are this high--as Drosophila data argue. Unfortunately, although molecular and evolutionary studies can give information on the total mutation rate, they cannot determine what fraction are deleterious. In addition, there are short discussions of the advantages of diploidy, anisogamy, and separate sexes.

Adaptation, Physiological↗
PubMed1993

How much do we know about spontaneous human mutation rates?

The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes of the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane [Ann Eugen 13:262-271, 1947] in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm, and may be considerably higher. The great mutation load implied by a rate of approximately 1 per zygote can be greatly ameliorated by quasi-truncation selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10(2) new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophila shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations.

Age Factors↗
PubMed1993

A molecular approach to estimating the human deleterious mutation rate.

We propose a method of measuring the human genomic deleterious mutation rate based on comparison of the rate of evolution per nucleotide per generation of neutral sequences, microN, with the overall rate of evolution of unique sequence DNA, microO. Data on microN, which are based on pseudogenes, permit an estimate of the total zygotic (twice the genomic) mutation rate, UT = 2 microNn = 2(2 x 10(-8)(3 x 10(9)) approximately 10(2), where n is the number of nucleotides per genome. Data on microO can be obtained by comparison of representative samples of relatively short homologous sequences from the genomes of Homo and a related species. The fraction of the genome that is controlled by negative selection is fS = (microN - microO)/microN and the deleterious zygotic mutation rate, the expected number of new deleterious alleles carried by a zygote, is US = UTfS. If fS > 0.01, US > 1, which would have important implications for human genetics and evolutionary biology.

Biological Evolution↗