Peter D Keightley

Summary

Publications

  1. ncbi Interference among deleterious mutations favours sex and recombination in finite populations
    Peter D Keightley
    Institute of Evolutionary Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    Nature 443:89-92. 2006
  2. pmc Genomic selective constraints in murid noncoding DNA
    Daniel J Gaffney
    Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 2:e204. 2006
  3. pmc MCALIGN2: faster, accurate global pairwise alignment of non-coding DNA sequences based on explicit models of indel evolution
    Jun Wang
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK
    BMC Bioinformatics 7:292. 2006
  4. pmc Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison
    Daniel L Halligan
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genome Res 16:875-84. 2006
  5. ncbi Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila
    Cathy Haag-Liautard
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    Nature 445:82-5. 2007
  6. doi Positive and negative selection in murine ultraconserved noncoding elements
    Daniel L Halligan
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Mol Biol Evol 28:2651-60. 2011
  7. pmc The role of advantageous mutations in enhancing the evolution of a recombination modifier
    Matthew Hartfield
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Genetics 184:1153-64. 2010
  8. ncbi Effect of divergence time and recombination rate on molecular evolution of Drosophila INE-1 transposable elements and other candidates for neutrally evolving sites
    Jun Wang
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    J Mol Evol 65:627-39. 2007
  9. doi Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes
    Lél Eöry
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Mol Biol Evol 27:177-92. 2010
  10. doi Patterns of DNA-sequence divergence between Drosophila miranda and D. pseudoobscura
    Sophie Marion de Procé
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JT, UK
    J Mol Evol 69:601-11. 2009

Detail Information

Publications56

  1. ncbi Interference among deleterious mutations favours sex and recombination in finite populations
    Peter D Keightley
    Institute of Evolutionary Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    Nature 443:89-92. 2006
    ..The mechanism supported by our results offers a robust and broadly applicable explanation for the evolutionary advantage of recombination and can explain the spread of costly sex...
  2. pmc Genomic selective constraints in murid noncoding DNA
    Daniel J Gaffney
    Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 2:e204. 2006
    ..91 per diploid genome, per generation. This estimated rate is over twice as large as a previous estimate in murids...
  3. pmc MCALIGN2: faster, accurate global pairwise alignment of non-coding DNA sequences based on explicit models of indel evolution
    Jun Wang
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK
    BMC Bioinformatics 7:292. 2006
    ..Unraveling the functional significance of non-coding DNA depends on how well we are able to align non-coding DNA sequences. However, the alignment of non-coding DNA sequences is more difficult than aligning protein-coding sequences...
  4. pmc Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison
    Daniel L Halligan
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genome Res 16:875-84. 2006
    ..Most deleterious mutations therefore occur in non-coding DNA, and these may make an important contribution to a wide variety of evolutionary processes...
  5. ncbi Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila
    Cathy Haag-Liautard
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    Nature 445:82-5. 2007
    ..2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction...
  6. doi Positive and negative selection in murine ultraconserved noncoding elements
    Daniel L Halligan
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Mol Biol Evol 28:2651-60. 2011
    ..This result suggests that there is widespread adaptation in mammalian conserved noncoding DNA elements, some of which have been implicated in the regulation of crucially important processes, including development...
  7. pmc The role of advantageous mutations in enhancing the evolution of a recombination modifier
    Matthew Hartfield
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Genetics 184:1153-64. 2010
    ..However, the strength of selection on a modifier is less than the summed strengths had there been deleterious mutations only and advantageous mutations only...
  8. ncbi Effect of divergence time and recombination rate on molecular evolution of Drosophila INE-1 transposable elements and other candidates for neutrally evolving sites
    Jun Wang
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    J Mol Evol 65:627-39. 2007
    ..Finally, we show that GC content for each site within INE-1 sequences has evolved toward an equilibrium value (approximately 33%) since insertion...
  9. doi Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes
    Lél Eöry
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Mol Biol Evol 27:177-92. 2010
    ..Including coding and noncoding sites, we estimate that the genomic deleterious mutation rate U = 4.2. The mutational load predicted under a multiplicative model is therefore about 99% in hominids...
  10. doi Patterns of DNA-sequence divergence between Drosophila miranda and D. pseudoobscura
    Sophie Marion de Procé
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JT, UK
    J Mol Evol 69:601-11. 2009
    ....
  11. ncbi Genetic instability of C. elegans comes naturally
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, UK
    Trends Genet 21:67-70. 2005
    ..Phenotypic assays of the same lines detected only a small proportion of mutations that were predicted to have evolutionarily significant fitness effects...
  12. pmc The scale of mutational variation in the murid genome
    Daniel J Gaffney
    Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genome Res 15:1086-94. 2005
    ..This raises questions about the biological mechanism(s) that produce new mutations and has implications for the study of male-driven evolution...
  13. pmc Inference of mutation parameters and selective constraint in mammalian coding sequences by approximate Bayesian computation
    Peter D Keightley
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, EH9 3JT, United Kingdom
    Genetics 187:1153-61. 2011
    ..Synonymous site selective constraint is weakest in murids, a surprising result, considering that murid effective population sizes are likely to be considerably higher than the other two taxa...
  14. doi Positive and negative selection on noncoding DNA close to protein-coding genes in wild house mice
    Athanasios Kousathanas
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Mol Biol Evol 28:1183-91. 2011
    ....
  15. pmc What can we learn about the distribution of fitness effects of new mutations from DNA sequence data?
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
    Philos Trans R Soc Lond B Biol Sci 365:1187-93. 2010
    ..Finally, we examine models involving slightly advantageous mutations. We show that the distribution of the absolute strength of selection is well estimated if mutations are assumed to be unconditionally deleterious...
  16. pmc Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster
    Cathy Haag-Liautard
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Biol 6:e204. 2008
    ..Strand-asymmetric mutation bias, coupled with selection to maintain specific nonsynonymous bases, therefore provides an explanation for the extreme base composition of the mitochondrial genome of Drosophila...
  17. pmc Evidence for pervasive adaptive protein evolution in wild mice
    Daniel L Halligan
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 6:e1000825. 2010
    ..Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans...
  18. pmc Patterns of evolutionary constraints in intronic and intergenic DNA of Drosophila
    Daniel L Halligan
    University of Edinburgh, School of Biological Sciences, Edinburgh EH9 3JT, UK
    Genome Res 14:273-9. 2004
    ....
  19. pmc Contributions of protein-coding and regulatory change to adaptive molecular evolution in murid rodents
    Daniel L Halligan
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 9:e1003995. 2013
    ..We conclude that although there appear to be many more adaptive noncoding changes, substitutions in proteins may dominate phenotypic evolution...
  20. pmc MCALIGN: stochastic alignment of noncoding DNA sequences based on an evolutionary model of sequence evolution
    Peter D Keightley
    University of Edinburgh, School of Biological Sciences, Ashworth Laboratories, Edinburgh EH9 3JT, UK Peter Keightley_at_ed ac uk
    Genome Res 14:442-50. 2004
    ..We show that there is excellent agreement between true and estimated alignments over a wide range of sequence divergences, and that the method outperforms other available alignment methods...
  21. doi Analysis and implications of mutational variation
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK
    Genetica 136:359-69. 2009
    ....
  22. ncbi Fine mapping of a murine growth locus to a 1.4-cM region and resolution of linked QTL
    Julian K Christians
    Institute of Cell, Animal and Population Biology, University of Edinburgh, Ashworth Laboratories, King s Buildings, West Mains Road, Edinburgh, EH9 3JT, UK
    Mamm Genome 15:482-91. 2004
    ..4-cM region, approximately the region from D1Mit451 to D1Mit219. The central QTL also affected tail length and body mass at 3 and 6 weeks of age, but to a lesser degree than 10-week tail length...
  23. pmc Inference of site frequency spectra from high-throughput sequence data: quantification of selection on nonsynonymous and synonymous sites in humans
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK
    Genetics 188:931-40. 2011
    ..Under the variable effects model, we infer that 11% of synonymous mutations are subject to strong purifying selection...
  24. pmc Joint inference of the distribution of fitness effects of deleterious mutations and population demography based on nucleotide polymorphism frequencies
    Peter D Keightley
    Institute of Evolutionary Biology, University of Edinburgh, United Kingdom
    Genetics 177:2251-61. 2007
    ....
  25. pmc Evolutionary constraints in conserved nongenic sequences of mammals
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genome Res 15:1373-8. 2005
    ....
  26. pmc Regulatory variation at glypican-3 underlies a major growth QTL in mice
    Fiona Oliver
    University of Edinburgh, Institute of Evolutionary Biology, School of Biological Sciences, Edinburgh, United Kingdom
    PLoS Biol 3:e135. 2005
    ..Furthermore, these findings show that small changes in gene expression can have substantial phenotypic effects...
  27. pmc A comparison of models to infer the distribution of fitness effects of new mutations
    Athanasios Kousathanas
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genetics 193:1197-208. 2013
    ..A lognormal DFE best explains the data for D. melanogaster, whereas we find evidence for a bimodal DFE in M. m. castaneus...
  28. doi Estimating the rate of adaptive molecular evolution when the evolutionary divergence between species is small
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK
    J Mol Evol 74:61-8. 2012
    ..This bias may be substantial if branch lengths are less than 10N (e) generations...
  29. pmc A method for inferring the rate of occurrence and fitness effects of advantageous mutations
    Adrian Schneider
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK
    Genetics 189:1427-37. 2011
    ..melanogaster are positively selected, with a scaled selection coefficient representing the product of the effective population size, N(e), and the strength of selection on heterozygous carriers of ∼2.5...
  30. pmc Intron size and exon evolution in Drosophila
    Gabriel Marais
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, UK
    Genetics 170:481-5. 2005
    ....
  31. ncbi Behavioural genetics: finding genes that cause complex trait variation
    Julian K Christians
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, UK
    Curr Biol 15:R19-21. 2005
    ..Identifying genes that influence phenotypic variation is extremely difficult, especially when the allelic variants only have a small effect. A recent study has used a novel approach to identify a gene that affects the behaviour of mice...
  32. ncbi Unexpected conserved non-coding DNA blocks in mammals
    Daniel J Gaffney
    Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, United Kingdom
    Trends Genet 20:332-7. 2004
    ..If functional, it could mark a turning point in the way we think about the evolution of the genome...
  33. ncbi Rates of molecular evolution in nuclear genes of east Mediterranean scorpions
    Benjamin Gantenbein
    School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, United Kingdom
    Evolution 58:2486-97. 2004
    ....
  34. pmc Evidence for widespread degradation of gene control regions in hominid genomes
    Peter D Keightley
    School of Biological Sciences, University of Edinburgh, United Kingdom
    PLoS Biol 3:e42. 2005
    ..This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees...
  35. pmc Nuclear gene variation in wild brown rats
    Rob W Ness
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, EH9 3JT, United Kingdom
    G3 (Bethesda) 2:1661-4. 2012
    ....
  36. pmc Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genome Res 19:1195-201. 2009
    ..Of seven short indel mutations confirmed, six were deletions, consistent with the deletion bias that is thought to exist in Drosophila...
  37. pmc Faster-X adaptive protein evolution in house mice
    Athanasios Kousathanas
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genetics 196:1131-43. 2014
    ..We discuss how our results help to explain the large effect of the X chromosome in speciation. ..
  38. pmc Estimation of the spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family
    Peter D Keightley
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genetics 196:313-20. 2014
    ..We also detected three short deletion mutations and no insertions, giving a deletion mutation rate of 1.2 × 10(-9) (95% confidence interval = 0.7 × 10(-9) - 11 × 10(-9)). ..
  39. doi Current hypotheses for the evolution of sex and recombination
    Matthew Hartfield
    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
    Integr Zool 7:192-209. 2012
    ..However, there is still a need to collect more data from natural populations and experimental studies, which can be used to test different hypotheses...
  40. doi The maintenance of obligate sex in finite, structured populations subject to recurrent beneficial and deleterious mutation
    Matthew Hartfield
    Laboratoire MIVEGEC UMR CNRS 5290, UR IRD 224, UM1, UM2, 911 Avenue Agropolis, B P 64501, 34394 Montpellier Cedex 5, France
    Evolution 66:3658-69. 2012
    ..g., when arrayed along one dimension), although this effect is often modest, especially if some long-distance dispersal is present...
  41. ncbi DNA sequence error rates in Genbank records estimated using the mouse genome as a reference
    Philipp L Wesche
    University of Edinburgh, School of Biological Sciences, Ashworth Laboratories, UK
    DNA Seq 15:362-4. 2004
    ..The frequency of insertion-deletion (indel) errors in non-coding DNA approaches that of single nucleotide errors in non-coding DNA, whereas indel errors are uncommon in coding sequences...
  42. ncbi Toward a realistic model of mutations affecting fitness
    Peter D Keightley
    University of Edinburgh, Institute of Cell, Animal and Population Biology, West Mains Road, Edinburgh EH9 3JT, United Kingdom
    Evolution 57:683-5; discussion 686-9. 2003
    ..We evaluate this in the light of data from other MA experiments, along with molecular evidence, that suggest the vast majority of new mutations are deleterious...
  43. ncbi Estimating numbers of EMS-induced mutations affecting life history traits in Caenorhabditis elegans in crosses between inbred sublines
    Daniel L Halligan
    Institute of Cell, Animal and Population Biology, University of Edinburgh, UK
    Genet Res 82:191-205. 2003
    ..Nonetheless, given that we expect there to be many mutations induced per line, our results support the hypothesis that mutations vary widely in their effects...
  44. pmc Estimate of the spontaneous mutation rate in Chlamydomonas reinhardtii
    Rob W Ness
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genetics 192:1447-54. 2012
    ..reinhardtii genome is very high. Our estimate is only the second direct estimate of the mutation rate from plants and among the lowest spontaneous base-substitution rates known in eukaryotes...
  45. ncbi How many lethal alleles?
    Daniel L Halligan
    Institute of Cell, Animal and Population Biology, University of Edinburgh, EH9 3JT, Edinburgh, UK
    Trends Genet 19:57-9. 2003
    ..A new study has revealed unexpectedly low numbers of segregating lethal alleles in two species of fish. More experiments are needed, however, to know whether this result is general...
  46. ncbi Characterization of a QTL affecting skeletal size in mice
    Julian K Christians
    Institute of Cell, Animal and Population Biology, University of Edinburgh, Ashworth Laboratories, King s Buildings, West Mains Road, UK
    Mamm Genome 14:175-83. 2003
    ..No significant effect was found on the number of bones in the tail or on the dimensions of the ulna, skull, or first vertebra...
  47. pmc Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents
    Peter D Keightley
    Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, United Kingdom
    Proc Natl Acad Sci U S A 100:13402-6. 2003
    ..Deleterious mutations in noncoding DNA have predominantly quantitative effects and could be an important source of the burden of complex genetic disease variation in human populations...
  48. ncbi Quantifying the slightly deleterious mutation model of molecular evolution
    Adam Eyre-Walker
    Centre for the Study of Evolution and School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK
    Mol Biol Evol 19:2142-9. 2002
    ..Only approximately 10% or fewer of mutations seem to behave as SDMs, but SDMs could comprise a substantial fraction of mutations in protein-coding genes that have a chance of becoming fixed between species...
  49. pmc Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals
    Daniel J Gaffney
    McGill University and Genome Quebec Innovation Centre, 740 ave Dr Penfield Rm 7208, Montreal, Quebec, H3A 1A4, Canada
    BMC Evol Biol 8:265. 2008
    ..Although it likely that this procedure is biased, it is generally assumed that the bias is negligible if species are very closely related...
  50. pmc Understanding the degradation of hominid gene control
    Peter D Keightley
    PLoS Comput Biol 2:e19; author reply e26. 2006
  51. pmc Comparing analysis methods for mutation-accumulation data
    Peter D Keightley
    Genetics 167:551-3. 2004
  52. ncbi Genetic complexity of an obesity QTL ( Fob3) revealed by detailed genetic mapping
    Ioannis M Stylianou
    Roslin Institute Edinburgh, Roslin, EH25 9PS, Scotland, UK
    Mamm Genome 15:472-81. 2004
    ....
  53. ncbi Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice
    Catherine B Millar
    Wellcome Trust Centre for Cell Biology, The King s Buildings, Edinburgh University, Edinburgh EH9 3JR, UK
    Science 297:403-5. 2002
    ..On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --> TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo...
  54. pmc Patterns of selective constraints in noncoding DNA of rice
    Xingyi Guo
    Institute of Crop Science and Institute of Bioinformatics, Zhejiang University, Hangzhou 310029, China
    BMC Evol Biol 7:208. 2007
    ..Here, we investigate selective constraints in a recent segmental duplication that includes 605 paralogous intron pairs that occurred about 7 million years ago in rice (O. sativa)...
  55. ncbi Evolution of genes and genomes on the Drosophila phylogeny
    Andrew G Clark
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
    Nature 450:203-18. 2007
    ..These may prove to underlie differences in the ecology and behaviour of these diverse species...
  56. ncbi The distribution of fitness effects of new mutations
    Adam Eyre-Walker
    Centre for the Study of Evolution, University of Sussex, Brighton, BN1 9QG, UK
    Nat Rev Genet 8:610-8. 2007
    ....