Skip to main content
Genetics logoLink to Genetics
. 2002 Dec;162(4):2017–2024. doi: 10.1093/genetics/162.4.2017

Changing effective population size and the McDonald-Kreitman test.

Adam Eyre-Walker 1
PMCID: PMC1462352  PMID: 12524367

Abstract

Artifactual evidence of adaptive amino acid substitution can be generated within a McDonald-Kreitman test if some amino acid mutations are slightly deleterious and there has been an increase in effective population size. Here I investigate the conditions under which this occurs. I show that fairly small increases in effective population size can generate artifactual evidence of positive selection if there is no selection upon synonymous codon use. This problem is exacerbated by the removal of low-frequency polymorphisms. However, selection on synonymous codon use restricts the conditions under which artifactual evidence of adaptive evolution is produced.

Full Text

The Full Text of this article is available as a PDF (120.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akashi H. Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics. 1999 Jan;151(1):221–238. doi: 10.1093/genetics/151.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akashi H. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics. 1996 Nov;144(3):1297–1307. doi: 10.1093/genetics/144.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akashi H., Schaeffer S. W. Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. Genetics. 1997 May;146(1):295–307. doi: 10.1093/genetics/146.1.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andolfatto P. Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol. 2001 Mar;18(3):279–290. doi: 10.1093/oxfordjournals.molbev.a003804. [DOI] [PubMed] [Google Scholar]
  5. Begun D. J., Aquadro C. F. African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature. 1993 Oct 7;365(6446):548–550. doi: 10.1038/365548a0. [DOI] [PubMed] [Google Scholar]
  6. Begun D. J. The frequency distribution of nucleotide variation in Drosophila simulans. Mol Biol Evol. 2001 Jul;18(7):1343–1352. doi: 10.1093/oxfordjournals.molbev.a003918. [DOI] [PubMed] [Google Scholar]
  7. Bulmer M. The selection-mutation-drift theory of synonymous codon usage. Genetics. 1991 Nov;129(3):897–907. doi: 10.1093/genetics/129.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. doi: 10.1017/s0016672300032365. [DOI] [PubMed] [Google Scholar]
  9. Chen F. C., Li W. H. Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am J Hum Genet. 2001 Jan 15;68(2):444–456. doi: 10.1086/318206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eyre-Walker A., Hurst L. D. The evolution of isochores. Nat Rev Genet. 2001 Jul;2(7):549–555. doi: 10.1038/35080577. [DOI] [PubMed] [Google Scholar]
  11. Eyre-Walker Adam, Keightley Peter D., Smith Nick G. C., Gaffney Daniel. Quantifying the slightly deleterious mutation model of molecular evolution. Mol Biol Evol. 2002 Dec;19(12):2142–2149. doi: 10.1093/oxfordjournals.molbev.a004039. [DOI] [PubMed] [Google Scholar]
  12. Fay J. C., Wyckoff G. J., Wu C. I. Positive and negative selection on the human genome. Genetics. 2001 Jul;158(3):1227–1234. doi: 10.1093/genetics/158.3.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fay Justin C., Wyckoff Gerald J., Wu Chung-I. Testing the neutral theory of molecular evolution with genomic data from Drosophila. Nature. 2002 Feb 28;415(6875):1024–1026. doi: 10.1038/4151024a. [DOI] [PubMed] [Google Scholar]
  14. Jenkins D. L., Ortori C. A., Brookfield J. F. A test for adaptive change in DNA sequences controlling transcription. Proc Biol Sci. 1995 Aug 22;261(1361):203–207. doi: 10.1098/rspb.1995.0137. [DOI] [PubMed] [Google Scholar]
  15. Keightley P. D., Eyre-Walker A. Deleterious mutations and the evolution of sex. Science. 2000 Oct 13;290(5490):331–333. doi: 10.1126/science.290.5490.331. [DOI] [PubMed] [Google Scholar]
  16. Kliman R. M. Recent selection on synonymous codon usage in Drosophila. J Mol Evol. 1999 Sep;49(3):343–351. doi: 10.1007/pl00006557. [DOI] [PubMed] [Google Scholar]
  17. McDonald J. H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. doi: 10.1038/351652a0. [DOI] [PubMed] [Google Scholar]
  18. Nachman M. W., Brown W. M., Stoneking M., Aquadro C. F. Nonneutral mitochondrial DNA variation in humans and chimpanzees. Genetics. 1996 Mar;142(3):953–963. doi: 10.1093/genetics/142.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Otto S. P., Whitlock M. C. The probability of fixation in populations of changing size. Genetics. 1997 Jun;146(2):723–733. doi: 10.1093/genetics/146.2.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sawyer S. A., Hartl D. L. Population genetics of polymorphism and divergence. Genetics. 1992 Dec;132(4):1161–1176. doi: 10.1093/genetics/132.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith Nick G. C., Eyre-Walker Adam. Adaptive protein evolution in Drosophila. Nature. 2002 Feb 28;415(6875):1022–1024. doi: 10.1038/4151022a. [DOI] [PubMed] [Google Scholar]
  22. Wise C. A., Sraml M., Easteal S. Departure from neutrality at the mitochondrial NADH dehydrogenase subunit 2 gene in humans, but not in chimpanzees. Genetics. 1998 Jan;148(1):409–421. doi: 10.1093/genetics/148.1.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wright S. The Distribution of Gene Frequencies Under Irreversible Mutation. Proc Natl Acad Sci U S A. 1938 Jul;24(7):253–259. doi: 10.1073/pnas.24.7.253. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES