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The distribution of fitness effects of new mutations

Nature Reviews Genetics volume 8, pages 610–618 (2007)Cite this article

Key Points

  • The distribution of fitness effects (DFE) is a fundamental entity in genetics that describes what proportion of new mutations are advantageous, neutral or deleterious.

  • The shape of the DFE varies between species and depends on factors such as population size and genome size.

  • The DFE differs between coding and non-coding DNA.

  • Advantageous mutations are rare.

  • The DFE of strongly advantageous mutations has an exponential distribution.

  • The DFE of deleterious mutations is a complex, multi-modal distribution.

Abstract

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 non-coding DNA. Despite these differences between species and genomic regions, some general principles have emerged: advantageous mutations are rare, and those that are strongly selected are exponentially distributed; and the DFE of deleterious mutations is complex and multi-modal.

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Figure 1: The distribution of fitness effects of random mutations in vesicular stomatitis virus.
Figure 2: The distribution of fitnesses among yeast lines.
Figure 3: The distribution of fitness effects of new amino-acid-changing mutations in humans.
Figure 4: The evolution of the distribution of fitness effects (DFE) of advantageous mutations.

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Acknowledgements

We thank M. Whitlock, S. Otto, A. Betancourt and four anonymous referees for many helpful comments on the manuscript. A.E.W. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the National Evolutionary Synthesis Center. P.K. was supported by the Wellcome Trust and the BBSRC.

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Authors and Affiliations

  1. Centre for the Study of Evolution, University of Sussex, Brighton, 9QG, BN1, UK

    Adam Eyre-Walker

  2. National Evolutionary Synthesis Center, Durham, 27705, North Carolina, USA

    Adam Eyre-Walker

  3. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, EH9 3JT, UK

    Peter D. Keightley

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Correspondence to Adam Eyre-Walker.

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Glossary

Muller's ratchet

The process by which a genome with little or no recombination degenerates owing to the stochastic loss of the allelic class with fewest deleterious mutations.

Kurtosis

The peakedness of the distribution.

Effective population size

The population size of randomly mating individuals that would behave, in a population genetic sense, as the population being studied. For example, the genetic diversity in human populations is the same as one would find in 10,000 randomly mating individuals.

Leptokurtic

Used here to refer to distributions that are more peaked than an exponential distribution.

Multi-modal

A distribution with more than one peak or mode.

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Eyre-Walker, A., Keightley, P. The distribution of fitness effects of new mutations. Nat Rev Genet 8, 610–618 (2007). https://doi.org/10.1038/nrg2146

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