# Peter D. Keightley
**Peter D. Keightley** is an evolutionary geneticist at the [University of Edinburgh](https://www.edgepedia.org/university-of-edinburgh) who studies how often spontaneous mutations occur and how they affect fitness, work that allows more accurate estimates of the deleterious mutation rate in a genome.[1](https://royalsociety.org/people/peter-keightley-11729/) He became a Professor in the School of Biological Sciences and was elected a [Fellow of the Royal Society](https://www.edgepedia.org/fellow-of-the-royal-society) in 2014.[1](https://royalsociety.org/people/peter-keightley-11729/) • [2](https://www.research.ed.ac.uk/en/projects/denovomut-an-integrated-approach-to-understanding-the-impact-of-d-3/)
| Fact | Detail |
|---|---|
| Field | Evolutionary genetics of quantitative traits and spontaneous mutations[1](https://royalsociety.org/people/peter-keightley-11729/) |
| Position | Professor, School of Biological Sciences, University of Edinburgh[2](https://www.research.ed.ac.uk/en/projects/denovomut-an-integrated-approach-to-understanding-the-impact-of-d-3/) |
| Training | PhD, University of Edinburgh, 1988, on quantitative genetic variation[3](http://hdl.handle.net/1842/12340) |
| Signature work | "High genomic deleterious mutation rates in hominids" (Nature, 1999); "Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila" (Nature, 2007)[4](https://www.nature.com/articles/16915) • [5](https://www.homepages.ed.ac.uk/pkeightl/publications/haag-liautard_etal2007.pdf) |
| Human mutation rate | Direct estimates give μ ≈ 1.1 × 10−8 per nucleotide per generation, about 70 new mutations per diploid genome[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3276617/) |
| Deleterious rate | U ≈ 2.2 per diploid human genome per generation (2012 review)[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3276617/) |
| Honour | Fellow of the Royal Society, elected 2014[1](https://royalsociety.org/people/peter-keightley-11729/) |
## Career and training
According to the dissertation itself, Keightley's doctoral dissertation, *Studies of quantitative genetic variation*, was deposited at the University of Edinburgh in 1988; it modeled the genetic variance maintained in quantitative traits under the joint effects of mutation, selection, linkage, and genetic drift.[3](http://hdl.handle.net/1842/12340) He has remained at Edinburgh throughout his career, and his 1999 Nature paper carried the affiliation of the Institute of Cell, Animal, and Population Biology; later work is affiliated with the Institute of Evolutionary Biology.[4](https://www.nature.com/articles/16915) • [5](https://www.homepages.ed.ac.uk/pkeightl/publications/haag-liautard_etal2007.pdf)
His laboratory is currently funded by the [Biotechnology](https://www.edgepedia.org/biotechnology) and Biological Sciences Research Council (BBSRC). Grants held at Edinburgh include £442,787 for "Underpinning UK Bioscience Research with high-throughput single molecule sequencing", alongside projects on genome evolution in *Drosophila* and on quantifying functional constraints in the mammalian genome.[7](https://gtr.ukri.org/person/00AF0809-D14D-4147-BE92-6FC2CF313B28) He is Principal Investigator of DENOVOMUT, a project on the impact of de novo mutations on the mammalian genome, and of a project on spontaneous mutational variation for fitness in *Chlamydomonas*.[2](https://www.research.ed.ac.uk/en/projects/denovomut-an-integrated-approach-to-understanding-the-impact-of-d-3/) • [8](https://www.research.ed.ac.uk/en/projects/the-nature-of-spontaneous-mutational-variation-for-fitness-in-chl/)
## Representative work
The 1999 Nature paper "High genomic deleterious mutation rates in hominids" compared human, chimpanzee, and gorilla DNA sequences and estimated that an average of 4.2 amino-acid-altering mutations per diploid per generation had occurred in the human lineage since the split from chimpanzees.[4](https://www.nature.com/articles/16915) At least 38% of these were estimated to have been eliminated by natural selection, implying more than 1.6 new deleterious mutations per diploid genome per generation (U = 1.6 ± 0.8 for humans, 1.7 ± 0.8 for chimpanzees, 1.2 ± 0.6 for gorillas).[4](https://www.nature.com/articles/16915) In their 1999 Nature paper "High genomic deleterious mutation rates in hominids," the authors concluded that the deleterious mutation rate in protein-coding sequences alone is close to the upper limit tolerable by a species with a low reproductive rate such as humans, and suggested that deleterious effects may combine synergistically.[4](https://www.nature.com/articles/16915)
The 2007 Nature paper "Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila" scanned 20,002,585 base pairs from three sets of *Drosophila melanogaster* mutation-accumulation lines using denaturing high-performance liquid chromatography, detected 37 mutation events, and estimated a per-nucleotide rate u = 8.4 × 10−9 per generation; multiplying by the deleterious fraction gave a genomic deleterious mutation rate U of 1.2 per diploid genome.[5](https://www.homepages.ed.ac.uk/pkeightl/publications/haag-liautard_etal2007.pdf)
A 2012 review in *Genetics*, "Rates and Fitness Consequences of New Mutations in Humans", synthesized the direct estimates then available: pedigree and family-sequencing studies give a per-nucleotide rate of about 1.1 × 10−8 per generation, roughly twofold lower than estimates based on human–chimp divergence, implying about 70 new mutations per diploid genome per generation, mostly arising in the paternal line.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3276617/) The review estimated U ≈ 2.2 for the whole diploid genome and about 0.35 for amino-acid-changing mutations, and argued that an accumulation of new deleterious mutations is unlikely to cause a detectable decline in human population fitness in the foreseeable future.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3276617/)
## Mutation-accumulation experiments and methods for inferring selection
Keightley's early work established the statistical machinery for extracting mutation rates from mutation-accumulation (MA) experiments, in which lines are kept small so that selection is relaxed and mutations accumulate nearly neutrally. A 1994 *Genetics* paper, written at the Institute of Cell, Animal, and Population Biology, applied maximum likelihood to MA data on viability in *Drosophila melanogaster*, estimating minimum mutation rates of 0.14 and 0.068 events per generation on chromosome 2 and finding that distributions of mutational effects are highly leptokurtic, so a model of equal effects fits poorly.[9](https://doi.org/10.1093/genetics/138.4.1315) Whole-genome sequencing of three *Drosophila* MA lines in 2009 mapped 174 single-nucleotide mutations, giving a rate of 3.5 × 10−9 per site per generation.[10](https://www.homepages.ed.ac.uk/pkeightl/publications/keightley-etal-2009.pdf)
For inferring selection from sequence data, Keightley developed maximum-likelihood methods for estimating the distribution of fitness effects (DFE) of new mutations. A 2007 *Genetics* paper introduced a method, based on allele-frequency distributions generated by transition matrix methods, that estimates the DFE while simultaneously fitting a demographic model, applied to amino-acid-changing mutations in humans and *Drosophila*.[11](https://europepmc.org/articles/PMC2219502) A 2010 analysis of sequencing design showed that, for a fixed sequencing effort, the optimum strategy for DFE inference is to sequence about 10 alleles, and that single-gene DFEs in humans and *Drosophila* cannot be reliably estimated unless hundreds or thousands of alleles are sequenced.[13](https://royalsocietypublishing.org/doi/10.1098/rstb.2009.0266)
## Sex, recombination and current interests
The Royal Society cites Keightley's current interests as explaining the evolution and perseverance of sex and genetic recombination as a means of reproduction.[1](https://royalsociety.org/people/peter-keightley-11729/) The 2007 *Drosophila* estimate bears directly on this question: U = 1.2 was noted by its authors to seem too low for deterministic mutation-selection balance alone to maintain sex against a twofold cost, while fitness-based estimates of U differ widely between species, from about 0.01 in *Caenorhabditis elegans* to about 0.6–1.0 in *Drosophila*.[5](https://www.homepages.ed.ac.uk/pkeightl/publications/haag-liautard_etal2007.pdf)
## References
1. Professor Peter Keightley FRS. Royal Society. https://royalsociety.org/people/peter-keightley-11729/
2. DENOVOMUT: an integrated approach to understanding the impact of de novo mutations on the mammalian genome. University of Edinburgh Research Explorer. https://www.research.ed.ac.uk/en/projects/denovomut-an-integrated-approach-to-understanding-the-impact-of-d-3/
3. Studies of quantitative genetic variation (doctoral dissertation, 1988). University of Edinburgh ERA. http://hdl.handle.net/1842/12340
4. High genomic deleterious mutation rates in hominids. Nature 1999. https://www.nature.com/articles/16915
5. Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 2007. https://www.homepages.ed.ac.uk/pkeightl/publications/haag-liautard_etal2007.pdf
6. Rates and Fitness Consequences of New Mutations in Humans. Genetics 2012. https://pmc.ncbi.nlm.nih.gov/articles/PMC3276617/
7. Peter Keightley. UKRI Gateway to Research. https://gtr.ukri.org/person/00AF0809-D14D-4147-BE92-6FC2CF313B28
8. The nature of spontaneous mutational variation for fitness in Chlamydomonas. University of Edinburgh Research Explorer. https://www.research.ed.ac.uk/en/projects/the-nature-of-spontaneous-mutational-variation-for-fitness-in-chl/
9. The distribution of mutation effects on viability in Drosophila melanogaster. Genetics 1994. https://doi.org/10.1093/genetics/138.4.1315
10. Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines. Genome Research 2009. https://www.homepages.ed.ac.uk/pkeightl/publications/keightley-etal-2009.pdf
11. Joint inference of the distribution of fitness effects and population demography. Genetics 2007. https://europepmc.org/articles/PMC2219502
12. The Distribution of Fitness Effects of New Deleterious Amino Acid Mutations in Humans. https://pmc.ncbi.nlm.nih.gov/articles/PMC1526495/
13. What can we learn about the distribution of fitness effects of new mutations from DNA sequence data? Phil. Trans. R. Soc. B 2010. https://royalsocietypublishing.org/doi/10.1098/rstb.2009.0266
14. Estimates of the Mutation Rate per Year Can Explain Why the Molecular Clock Depends on Generation Time. Molecular Biology and Evolution 2025. https://doi.org/10.1093/molbev/msaf069
15. Revising the human mutation rate: implications for understanding human evolution. Nature Reviews Genetics 2013. https://www.nature.com/articles/nrg3295
16. Mutation rate variation in multicellular eukaryotes: causes and consequences. Nature Reviews Genetics 2008. https://preview-www.nature.com/articles/nrg2158
17. Perspective: Spontaneous Deleterious Mutation. Evolution 1999. https://www.bio.fsu.edu/~dhoule/Publications/Lynch@@99.pdf
---
*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in genetics, genomics, and genome engineering › Population and evolutionary genetics › Theoretical population geneticists*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026; Sep 30, 2026 · Edited: Sep 25, 2026; Sep 30, 2026; Oct 11, 2026 · Last review: Sep 30, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license