How much do we know about spontaneous human mutation rates?

  title={How much do we know about spontaneous human mutation rates?},
  author={James F. Crow},
  journal={Environmental and Molecular Mutagenesis},
  • J. Crow
  • Published 1993
  • Biology
  • Environmental and Molecular Mutagenesis
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 on 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… 

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

  • J. Crow
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
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

Characteristics, causes and evolutionary consequences of male-biased mutation

  • H. Ellegren
  • Biology
    Proceedings of the Royal Society B: Biological Sciences
  • 2006
The concept of male-biased mutation has implications for important aspects of evolutionary biology such as mate choice in relation to mutation load, sexual selection and the maintenance of genetic diversity despite strong directional selection.

Major impacts of gonadal mosaicism on hereditary risk estimation, origin of hereditary diseases, and evolution

Computer simulations of control experiments involving 57.4 million offspring, based on vast amounts of historical data, show that because of gonadal mosaicism, the total frequency of spontaneous mutations per generation is much higher than has been thought.

Mutation load and human longevity.

Measurements of spontaneous rates of mutations in the recent past and the near future

The methods used in the past are reviewed with an emphasis on next generation sequencing, which may soon make the accurate measurement of spontaneous mutation rates a matter of routine.

Variation in genome-wide mutation rates within and between human families

This is the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios, and observations suggest considerable variation in mutation rates within and between families.

Comparisons of Spontaneous Mutation Rates and Estimates of Numbers of Cell Divisions in the Germlines of Three Metazoans.

Comparisons of mutation rates per cell division, along with data regarding parental origin of human mutations and male-driven molecular evolution, provide support for an effect of cell division upon mutation rates, but with additional factors which cause time-dependent mechanism for mutation rates.

The distribution of fitness effects of new mutations

The distribution of fitness effects (DFE) of new mutations is a fundamental entity in genetics that has implications ranging from the genetic basis of complex disease to the stability of the



The genomic mutation rate for fitness in Drosophila

The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation and the average homozygous effect of a new mutation of minor effect in Drosophila melanogaster.

Mutation rate and dominance of genes affecting viability in Drosophila melanogaster.

That these mutants have a disproportionately large heterozygous effect on total fitness (as well as on the viability component thereof) is shown by the low ratio of the genetic load in equilibrium homozygote to that of new mutant homozygotes.


The viability in the Drosophila male of X-chromosomes irradiated in sperm shows a slight reduction, which is, nevertheless, highly significant, and mutations of very low magnitude and very high frequency are indicated.

Spontaneous mutation in man.

One would expect that mutation, and especially “spontaneous” mutation, i.e., that occurring naturally and without any detectable external reasons, would attract the research activity of many biologists, especially geneticists, but this is not the case.

Evidence for the Partial Dominance of Recessive Lethal Genes in Natural Populations of Drosophila

Data on mutation rates, frequency of lethal chromosomes, and proportion of allelism among lethal chromosomes from wild Drosophila populations is used to make an indirect estimate of what the effective dominance of lethals must be in nature.

A constant rate of spontaneous mutation in DNA-based microbes.

  • J. Drake
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
A nearly invariant microbial mutation rate appears to have evolved in several DNA-based haploid microbes, likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs of further reducing mutation rates.

Homozygous viability and fertility loads in Drosophila melanogaster.

Interest centers upon the relative impact of the group of genes with individually slight effects in contrast to those with drastic effects, and an additional aspect of fitness, that of female and male fertility, has also been investigated.

The influence of epistasis on homozygous viability depression in Drosophila melanogaster.

The results to be presented here show no statistically significant systematic interaction between mildly deleterious homozygotes on the two major autosomes, indicating that within a chromosome there is a barely significant synergistic interaction.

The rate with which spontaneous mutation alters the electrophoretic mobility of polypeptides.

  • J. NeelC. Satoh R. Hazama
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1986
Studies of a Japanese population, involving a total of 539,170 locus tests distributed over 36 polypeptides, yielded three presumptive spontaneous mutations altering the electrophoretic mobility of

Ageing and mutation in plants

It is reported here that the mutation rates in the long-lived mangrove are 25 times higher than in the annuals barley and buckwheat, leading to the prediction that long- lived plants will have higher mutation rates per generation than short-lived plants.