Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2001 Dec;159(4):1789–1804. doi: 10.1093/genetics/159.4.1789

The probability of preservation of a newly arisen gene duplicate.

M Lynch 1, M O'Hely 1, B Walsh 1, A Force 1
PMCID: PMC1461922  PMID: 11779815

Abstract

Newly emerging data from genome sequencing projects suggest that gene duplication, often accompanied by genetic map changes, is a common and ongoing feature of all genomes. This raises the possibility that differential expansion/contraction of various genomic sequences may be just as important a mechanism of phenotypic evolution as changes at the nucleotide level. However, the population-genetic mechanisms responsible for the success vs. failure of newly arisen gene duplicates are poorly understood. We examine the influence of various aspects of gene structure, mutation rates, degree of linkage, and population size (N) on the joint fate of a newly arisen duplicate gene and its ancestral locus. Unless there is active selection against duplicate genes, the probability of permanent establishment of such genes is usually no less than 1/(4N) (half of the neutral expectation), and it can be orders of magnitude greater if neofunctionalizing mutations are common. The probability of a map change (reassignment of a key function of an ancestral locus to a new chromosomal location) induced by a newly arisen duplicate is also generally >1/(4N) for unlinked duplicates, suggesting that recurrent gene duplication and alternative silencing may be a common mechanism for generating microchromosomal rearrangements responsible for postreproductive isolating barriers among species. Relative to subfunctionalization, neofunctionalization is expected to become a progressively more important mechanism of duplicate-gene preservation in populations with increasing size. However, even in large populations, the probability of neofunctionalization scales only with the square of the selective advantage. Tight linkage also influences the probability of duplicate-gene preservation, increasing the probability of subfunctionalization but decreasing the probability of neofunctionalization.

Full Text

The Full Text of this article is available as a PDF (189.9 KB).

Selected References

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

  1. Amador A., Juan E. Nonfixed duplication containing the Adh gene and a truncated form of the Adhr gene in the Drosophila funebris species group: different modes of evolution of Adh relative to Adhr in Drosophila. Mol Biol Evol. 1999 Nov;16(11):1439–1456. doi: 10.1093/oxfordjournals.molbev.a026056. [DOI] [PubMed] [Google Scholar]
  2. Bailey G. S., Poulter R. T., Stockwell P. A. Gene duplication in tetraploid fish: model for gene silencing at unlinked duplicated loci. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5575–5579. doi: 10.1073/pnas.75.11.5575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bancroft I. Duplicate and diverge: the evolution of plant genome microstructure. Trends Genet. 2001 Feb;17(2):89–93. doi: 10.1016/s0168-9525(00)02179-x. [DOI] [PubMed] [Google Scholar]
  4. Christiansen F. B., Frydenberg O. Selection-mutation balance for two nonallelic recessives producing an inferior double homozygote. Am J Hum Genet. 1977 Mar;29(2):195–207. [PMC free article] [PubMed] [Google Scholar]
  5. Clark A. G. Invasion and maintenance of a gene duplication. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2950–2954. doi: 10.1073/pnas.91.8.2950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dehal P., Predki P., Olsen A. S., Kobayashi A., Folta P., Lucas S., Land M., Terry A., Ecale Zhou C. L., Rash S. Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution. Science. 2001 Jul 6;293(5527):104–111. doi: 10.1126/science.1060310. [DOI] [PubMed] [Google Scholar]
  7. Dermitzakis E. T., Clark A. G. Differential selection after duplication in mammalian developmental genes. Mol Biol Evol. 2001 Apr;18(4):557–562. doi: 10.1093/oxfordjournals.molbev.a003835. [DOI] [PubMed] [Google Scholar]
  8. Dobzhansky T. Studies on Hybrid Sterility. II. Localization of Sterility Factors in Drosophila Pseudoobscura Hybrids. Genetics. 1936 Mar;21(2):113–135. doi: 10.1093/genetics/21.2.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Force A., Lynch M., Pickett F. B., Amores A., Yan Y. L., Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics. 1999 Apr;151(4):1531–1545. doi: 10.1093/genetics/151.4.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gu X., Li W. H. The size distribution of insertions and deletions in human and rodent pseudogenes suggests the logarithmic gap penalty for sequence alignment. J Mol Evol. 1995 Apr;40(4):464–473. doi: 10.1007/BF00164032. [DOI] [PubMed] [Google Scholar]
  11. Hughes A. L. The evolution of functionally novel proteins after gene duplication. Proc Biol Sci. 1994 May 23;256(1346):119–124. doi: 10.1098/rspb.1994.0058. [DOI] [PubMed] [Google Scholar]
  12. KIMURA M. On the probability of fixation of mutant genes in a population. Genetics. 1962 Jun;47:713–719. doi: 10.1093/genetics/47.6.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kent W. J., Zahler A. M. Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment. Genome Res. 2000 Aug;10(8):1115–1125. doi: 10.1101/gr.10.8.1115. [DOI] [PubMed] [Google Scholar]
  14. Kimura M., Ohta T. The Average Number of Generations until Fixation of a Mutant Gene in a Finite Population. Genetics. 1969 Mar;61(3):763–771. doi: 10.1093/genetics/61.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krakauer D. C., Nowak M. A. Evolutionary preservation of redundant duplicated genes. Semin Cell Dev Biol. 1999 Oct;10(5):555–559. doi: 10.1006/scdb.1999.0337. [DOI] [PubMed] [Google Scholar]
  16. Lange B. W., Langley C. H., Stephan W. Molecular evolution of Drosophila metallothionein genes. Genetics. 1990 Dec;126(4):921–932. doi: 10.1093/genetics/126.4.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lootens S., Burnett J., Friedman T. B. An intraspecific gene duplication polymorphism of the urate oxidase gene of Drosophila virilis: a genetic and molecular analysis. Mol Biol Evol. 1993 May;10(3):635–646. doi: 10.1093/oxfordjournals.molbev.a040028. [DOI] [PubMed] [Google Scholar]
  18. Lynch M., Conery J. S. The evolutionary fate and consequences of duplicate genes. Science. 2000 Nov 10;290(5494):1151–1155. doi: 10.1126/science.290.5494.1151. [DOI] [PubMed] [Google Scholar]
  19. Lynch M., Force A. The probability of duplicate gene preservation by subfunctionalization. Genetics. 2000 Jan;154(1):459–473. doi: 10.1093/genetics/154.1.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lynch M. Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol Biol Evol. 1996 Jan;13(1):209–220. doi: 10.1093/oxfordjournals.molbev.a025557. [DOI] [PubMed] [Google Scholar]
  21. Nowak M. A., Boerlijst M. C., Cooke J., Smith J. M. Evolution of genetic redundancy. Nature. 1997 Jul 10;388(6638):167–171. doi: 10.1038/40618. [DOI] [PubMed] [Google Scholar]
  22. Petrov D. A., Hartl D. L. High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups. Mol Biol Evol. 1998 Mar;15(3):293–302. doi: 10.1093/oxfordjournals.molbev.a025926. [DOI] [PubMed] [Google Scholar]
  23. Robin G. C., Russell R. J., Cutler D. J., Oakeshott J. G. The evolution of an alpha-esterase pseudogene inactivated in the Drosophila melanogaster lineage. Mol Biol Evol. 2000 Apr;17(4):563–575. doi: 10.1093/oxfordjournals.molbev.a026336. [DOI] [PubMed] [Google Scholar]
  24. Ryu S. L., Murooka Y., Kaneko Y. Reciprocal translocation at duplicated RPL2 loci might cause speciation of Saccharomyces bayanus and Saccharomyces cerevisiae. Curr Genet. 1998 May;33(5):345–351. doi: 10.1007/s002940050346. [DOI] [PubMed] [Google Scholar]
  25. Shimeld S. M. Gene function, gene networks and the fate of duplicated genes. Semin Cell Dev Biol. 1999 Oct;10(5):549–553. doi: 10.1006/scdb.1999.0336. [DOI] [PubMed] [Google Scholar]
  26. Stoltzfus A. On the possibility of constructive neutral evolution. J Mol Evol. 1999 Aug;49(2):169–181. doi: 10.1007/pl00006540. [DOI] [PubMed] [Google Scholar]
  27. Takahata N., Maruyama T. Polymorphism and loss of duplicate gene expression: a theoretical study with application of tetraploid fish. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4521–4525. doi: 10.1073/pnas.76.9.4521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wagner A. The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions. Genetics. 2000 Mar;154(3):1389–1401. doi: 10.1093/genetics/154.3.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Watterson G. A. On the time for gene silencing at duplicate Loci. Genetics. 1983 Nov;105(3):745–766. doi: 10.1093/genetics/105.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. de Jong W. W., Rydén L. Causes of more frequent deletions than insertions in mutations and protein evolution. Nature. 1981 Mar 12;290(5802):157–159. doi: 10.1038/290157a0. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES