Logo of procbhomepageaboutsubmitalertseditorial board
Proc Biol Sci. May 7, 2003; 270(1518): 921–928.
PMCID: PMC1691325

Site-specific selfish genes as tools for the control and genetic engineering of natural populations.


Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Full Text

The Full Text of this article is available as a PDF (206K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ashburner M, Misra S, Roote J, Lewis SE, Blazej R, Davis T, Doyle C, Galle R, George R, Harris N, et al. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999 Sep;153(1):179–219. [PMC free article] [PubMed]
  • Beerntsen BT, James AA, Christensen BM. Genetics of mosquito vector competence. Microbiol Mol Biol Rev. 2000 Mar;64(1):115–137. [PMC free article] [PubMed]
  • Bellaiche Y, Mogila V, Perrimon N. I-SceI endonuclease, a new tool for studying DNA double-strand break repair mechanisms in Drosophila. Genetics. 1999 Jul;152(3):1037–1044. [PMC free article] [PubMed]
  • Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol. 2001 Jan;21(1):289–297. [PMC free article] [PubMed]
  • Buchholz F, Stewart AF. Alteration of Cre recombinase site specificity by substrate-linked protein evolution. Nat Biotechnol. 2001 Nov;19(11):1047–1052. [PubMed]
  • Chandrasegaran S, Smith J. Chimeric restriction enzymes: what is next? Biol Chem. 1999 Jul-Aug;380(7-8):841–848. [PMC free article] [PubMed]
  • Chevalier BS, Stoddard BL. Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res. 2001 Sep 15;29(18):3757–3774. [PMC free article] [PubMed]
  • Chevalier Brett S, Kortemme Tanja, Chadsey Meggen S, Baker David, Monnat Raymond J, Stoddard Barry L. Design, activity, and structure of a highly specific artificial endonuclease. Mol Cell. 2002 Oct;10(4):895–905. [PubMed]
  • Goddard MR, Greig D, Burt A. Outcrossed sex allows a selfish gene to invade yeast populations. Proc Biol Sci. 2001 Dec 22;268(1485):2537–2542. [PMC free article] [PubMed]
  • Guo H, Karberg M, Long M, Jones JP, 3rd, Sullenger B, Lambowitz AM. Group II introns designed to insert into therapeutically relevant DNA target sites in human cells. Science. 2000 Jul 21;289(5478):452–457. [PubMed]
  • Hamilton WD. Extraordinary sex ratios. A sex-ratio theory for sex linkage and inbreeding has new implications in cytogenetics and entomology. Science. 1967 Apr 28;156(3774):477–488. [PubMed]
  • Hastings IM. Selfish DNA as a method of pest control. Philos Trans R Soc Lond B Biol Sci. 1994 May 28;344(1309):313–324. [PubMed]
  • Hickey WA, Craig GB., Jr Distortion of sex ratio in populations of Aedes aegypti. Can J Genet Cytol. 1966 Jun;8(2):260–278. [PubMed]
  • Ito Junitsu, Ghosh Anil, Moreira Luciano A, Wimmer Ernst A, Jacobs-Lorena Marcelo. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature. 2002 May 23;417(6887):452–455. [PubMed]
  • Jacquier A, Dujon B. An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene. Cell. 1985 Jun;41(2):383–394. [PubMed]
  • Koufopanou Vassiliki, Goddard Matthew R, Burt Austin. Adaptation for horizontal transfer in a homing endonuclease. Mol Biol Evol. 2002 Mar;19(3):239–246. [PubMed]
  • McKee BD, Handel MA. Sex chromosomes, recombination, and chromatin conformation. Chromosoma. 1993 Jan;102(2):71–80. [PubMed]
  • Miklos GL, Rubin GM. The role of the genome project in determining gene function: insights from model organisms. Cell. 1996 Aug 23;86(4):521–529. [PubMed]
  • Palumbi SR. Humans as the world's greatest evolutionary force. Science. 2001 Sep 7;293(5536):1786–1790. [PubMed]
  • Ribeiro JM, Kidwell MG. Transposable elements as population drive mechanisms: specification of critical parameter values. J Med Entomol. 1994 Jan;31(1):10–16. [PubMed]
  • Rong YS, Golic KG. Gene targeting by homologous recombination in Drosophila. Science. 2000 Jun 16;288(5473):2013–2018. [PubMed]
  • Rong Yikang S, Titen Simon W, Xie Heng B, Golic Mary M, Bastiani Michael, Bandyopadhyay Pradip, Olivera Baldomero M, Brodsky Michael, Rubin Gerald M, Golic Kent G. Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 2002 Jun 15;16(12):1568–1581. [PMC free article] [PubMed]
  • Santoro Stephen W, Schultz Peter G. Directed evolution of the site specificity of Cre recombinase. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4185–4190. [PMC free article] [PubMed]
  • Segal DJ, Dreier B, Beerli RR, Barbas CF., 3rd Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2758–2763. [PMC free article] [PubMed]
  • Seligman Lenny M, Chisholm Karen M, Chevalier Brett S, Chadsey Meggen S, Edwards Samuel T, Savage Jeremiah H, Veillet Adeline L. Mutations altering the cleavage specificity of a homing endonuclease. Nucleic Acids Res. 2002 Sep 1;30(17):3870–3879. [PMC free article] [PubMed]
  • Sweeny TL, Barr AR. Sex Ratio Distortion Caused by Meiotic Drive in a Mosquito, Culex pipiens L. Genetics. 1978 Mar;88(3):427–446. [PMC free article] [PubMed]
  • Takahashi Hidekazu, Fujiwara Haruhiko. Transplantation of target site specificity by swapping the endonuclease domains of two LINEs. EMBO J. 2002 Feb 1;21(3):408–417. [PMC free article] [PubMed]
  • Thomas DD, Donnelly CA, Wood RJ, Alphey LS. Insect population control using a dominant, repressible, lethal genetic system. Science. 2000 Mar 31;287(5462):2474–2476. [PubMed]
  • Turelli M, Hoffmann AA. Microbe-induced cytoplasmic incompatibility as a mechanism for introducing transgenes into arthropod populations. Insect Mol Biol. 1999 May;8(2):243–255. [PubMed]
  • Wenzlau JM, Saldanha RJ, Butow RA, Perlman PS. A latent intron-encoded maturase is also an endonuclease needed for intron mobility. Cell. 1989 Feb 10;56(3):421–430. [PubMed]
  • White NJ, Nosten F, Looareesuwan S, Watkins WM, Marsh K, Snow RW, Kokwaro G, Ouma J, Hien TT, Molyneux ME, et al. Averting a malaria disaster. Lancet. 1999 Jun 5;353(9168):1965–1967. [PubMed]
  • Wilson DS, Keefe AD, Szostak JW. The use of mRNA display to select high-affinity protein-binding peptides. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3750–3755. [PMC free article] [PubMed]

Articles from Proceedings of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...