The distribution of fitness effects of new mutations

@article{EyreWalker2007TheDO,
  title={The distribution of fitness effects of new mutations},
  author={A. Eyre-Walker and P. Keightley},
  journal={Nature Reviews Genetics},
  year={2007},
  volume={8},
  pages={610-618}
}
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 molecular clock. It has been studied by two different approaches: mutation accumulation and mutagenesis experiments, and the analysis of DNA sequence data. The proportion of mutations that are advantageous, effectively neutral and deleterious varies between species, and the DFE differs between coding and… Expand

Figures from this paper

Determining the factors driving selective effects of new nonsynonymous mutations
TLDR
It is shown that the theoretical models make distinct predictions about how the distribution of fitness effects of new mutations will differ between species, and that humans have a higher proportion of strongly deleterious mutations than Drosophila melanogaster. Expand
Direct inference of the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii
TLDR
The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution, and predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size. Expand
Inferring the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii
TLDR
The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution, and predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size. Expand
Spontaneous Mutation Accumulation Studies in Evolutionary Genetics
TLDR
Phenotypic assays of MA lines inform us about the nature of new mutational variation for quantitative traits and provide estimates of the genomic rate and the distribution of effects of new mutations, suggesting that the genomic mutation rate varies by several orders of magnitude and that the distributions of effects tends to be dominated by large-effect mutations. Expand
Inferring parameters of the distribution of fitness effects of new mutations when beneficial mutations are strongly advantageous and rare
TLDR
The results from this study suggest that the parameters of positively selected mutations obtained by analysis of the uSFS should be treated with caution and suggest that variability at linked sites should be used in conjunction with standing variability to estimate parameters of the distribution of fitness effects in the future. Expand
Mutational Robustness of Ribosomal Protein Genes
TLDR
Most mutations, whether synonymous or nonsynonymous, had significant fitness costs, thus overturning the prevailing dogma that most point mutations are either neutral or lethal and indicating that the mutations influenced messenger RNA structure and/or stability. Expand
Determining the factors driving selective effects of new nonsynonymous mutations
TLDR
It is shown that amino acid-changing mutations in humans are, on average, more deleterious than mutations in Drosophila, and it is demonstrated that the only theoretical model that is fully consistent with the results is Fisher’s geometrical model. Expand
Experimental Determination and Prediction of the Fitness Effects of Random Point Mutations in the Biosynthetic Enzyme HisA
TLDR
The effect of mutations can be masked by high expression levels, such that mutations that are deleterious to the function of the protein can still be neutral with regard to organism fitness if the protein is expressed at a sufficiently high level. Expand
Inferring Parameters of the Distribution of Fitness Effects of New Mutations When Beneficial Mutations Are Strongly Advantageous and Rare
TLDR
The results from this study suggest that the parameters of positively selected mutations obtained by analysis of the uSFS should be treated with caution and that variability at linked sites should be used in conjunction with standing variability to estimate parameters of the distribution of fitness effects in the future. Expand
Variation in Mutational Robustness between Different Proteins and the Predictability of Fitness Effects.
TLDR
It is suggested that the 33-fold higher average mutational robustness of ribosomal proteins is due to stronger selection for reduced costs of translational and transcriptional errors, and the fitness effects of amino acid substitutions can be predicted based on evolutionary conservation, but those weakly deleterious mutations are less reliably detected. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 120 REFERENCES
Inferring the distribution of mutational effects on fitness in Drosophila
TLDR
Several important parameters, such as the fraction of effectively neutral non-synonymous mutations and the harmonic mean of non-neutral selection coefficients, are robust to the form of the DDME. Expand
Distribution of fitness effects among beneficial mutations before selection in experimental populations of bacteria
TLDR
The results suggest that the initial step in adaptive evolution—the production of novel beneficial mutants from which selection sorts—is very general, being characterized by an approximately exponential distribution with many mutations of small effect and few of large effect. Expand
The Distribution of Fitness Effects of New Deleterious Amino Acid Mutations in Humans
TLDR
It is argued that the relaxation of natural selection due to modern medicine and reduced variance in family size is not likely to lead to a rapid decline in genetic quality, but that it will be very difficult to locate most of the genes involved in complex genetic diseases. Expand
Distributions of Beneficial Fitness Effects in RNA
TLDR
Testing the distribution of beneficial fitness effects with a quasi-empirical model of RNA evolution in which fitness is based on the secondary structures of molecules and their thermodynamic stabilities suggests that more complex statistical generalizations about beneficial mutations may be possible. Expand
The distribution of fitness effects among beneficial mutations.
TLDR
Using extreme value theory, this distribution of fitness effects among new beneficial mutations is derived and it is shown that it has two unexpected properties: first, the distribution of beneficial fitness effects at a gene is exponential, and second, it has the same mean regardless of the fitness of the present wild-type allele. Expand
Rate of deleterious mutation and the distribution of its effects on fitness in vesicular stomatitis virus
Despite their importance, the parameters describing the spontaneous deleterious mutation process have not been well described in many organisms. If mutations are important for the evolution of everyExpand
Fitness effects of advantageous mutations in evolving Escherichia coli populations.
  • M. Imhof, C. Schlotterer
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2001
TLDR
A novel marker system is used to trace adaptive events in an evolving Escherichia coli culture and to determine the selective advantage of those beneficial mutations and to estimate the rate of beneficial mutations to be 4 x 10(-9) per cell and generation. Expand
Quantifying the slightly deleterious mutation model of molecular evolution.
TLDR
The frequency and effects of slightly deleterious mutations (SDMs) are quantified by comparing the level of selective constraint in protein-coding genes of related species that have different present-day effective population sizes, implying that SDMs had become fixed. Expand
Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae.
TLDR
Like other recently tested model organisms, wild-type yeast have low mutation rates, with high mean fitness costs per mutation, and inactivation of mismatch repair increases the frequency of slightly deleterious mutations by approximately two orders of magnitude. Expand
Estimating Selection on Nonsynonymous Mutations
TLDR
Two methods for characterizing the fitness effects of deleterious, nonsynonymous mutations are developed, using polymorphism data from two related species, and a simple approximate method for estimating the harmonic mean selection coefficient from diversity data on a single species is described. Expand
...
1
2
3
4
5
...