Skip to main content
Genetics logoLink to Genetics
. 1994 Jul;137(3):837–843. doi: 10.1093/genetics/137.3.837

Gene Conversion between Unlinked Sequences in the Germline of Mice

J R Murti 1, M Bumbulis 1, J C Schimenti 1
PMCID: PMC1206043  PMID: 8088528

Abstract

Gene conversion between homologous sequences on non-homologous chromosomes (ectopic gene conversion) is remarkably frequent in fungi. It is thought to be a consequence of genome-wide homology scanning required to form synapses between homologous chromosomes. This activity provides a mechanism for concerted evolution of dispersed genes. Technical obstacles associated with mammalian systems have hitherto precluded investigations into ectopic gene conversion in the mammals. Here, we describe a binary transgenic mouse system to detect ectopic gene conversion in mice. Conversion events are visualized by histochemical staining of spermatids, and corroborated by polymerase chain reaction amplification of transgenes in spermatozoa. The results show that conversion between unlinked, hemizygous lacZ transgenes is frequent in the male germline, ranging from 0.1 to 0.7% of spermatids. Genomic location may affect the susceptibility to recombination, since the frequency varied between lines. The results suggest that homologous genes can undergo concerted evolution despite being genomically dispersed. However, mechanisms may exist to modulate this activity, enabling the divergence of duplicated genes.

Full Text

The Full Text of this article is available as a PDF (4.3 MB).

Selected References

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

  1. Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
  2. Bishop D. K., Park D., Xu L., Kleckner N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell. 1992 May 1;69(3):439–456. doi: 10.1016/0092-8674(92)90446-j. [DOI] [PubMed] [Google Scholar]
  3. Carpenter A. T. Gene conversion, recombination nodules, and the initiation of meiotic synapsis. Bioessays. 1987 May;6(5):232–236. doi: 10.1002/bies.950060510. [DOI] [PubMed] [Google Scholar]
  4. Cui X. F., Li H. H., Goradia T. M., Lange K., Kazazian H. H., Jr, Galas D., Arnheim N. Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9389–9393. doi: 10.1073/pnas.86.23.9389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engebrecht J., Hirsch J., Roeder G. S. Meiotic gene conversion and crossing over: their relationship to each other and to chromosome synapsis and segregation. Cell. 1990 Sep 7;62(5):927–937. doi: 10.1016/0092-8674(90)90267-i. [DOI] [PubMed] [Google Scholar]
  6. Fitch D. H., Mainone C., Goodman M., Slightom J. L. Molecular history of gene conversions in the primate fetal gamma-globin genes. Nucleotide sequences from the common gibbon, Hylobates lar. J Biol Chem. 1990 Jan 15;265(2):781–793. [PubMed] [Google Scholar]
  7. Haber J. E., Leung W. Y., Borts R. H., Lichten M. The frequency of meiotic recombination in yeast is independent of the number and position of homologous donor sequences: implications for chromosome pairing. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1120–1124. doi: 10.1073/pnas.88.4.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hess J. F., Fox M., Schmid C., Shen C. K. Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5970–5974. doi: 10.1073/pnas.80.19.5970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jinks-Robertson S., Petes T. D. Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes. Genetics. 1986 Nov;114(3):731–752. doi: 10.1093/genetics/114.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Keil R. L., McWilliams A. D. A gene with specific and global effects on recombination of sequences from tandemly repeated genes in Saccharomyces cerevisiae. Genetics. 1993 Nov;135(3):711–718. doi: 10.1093/genetics/135.3.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Letsou A., Liskay R. M. Effect of the molecular nature of mutation on the efficiency of intrachromosomal gene conversion in mouse cells. Genetics. 1987 Dec;117(4):759–769. doi: 10.1093/genetics/117.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liskay R. M., Letsou A., Stachelek J. L. Homology requirement for efficient gene conversion between duplicated chromosomal sequences in mammalian cells. Genetics. 1987 Jan;115(1):161–167. doi: 10.1093/genetics/115.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liskay R. M., Stachelek J. L. Evidence for intrachromosomal gene conversion in cultured mouse cells. Cell. 1983 Nov;35(1):157–165. doi: 10.1016/0092-8674(83)90218-0. [DOI] [PubMed] [Google Scholar]
  14. Meselson M. S., Radding C. M. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. doi: 10.1073/pnas.72.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mikus M. D., Petes T. D. Recombination between genes located on nonhomologous chromosomes in Saccharomyces cerevisiae. Genetics. 1982 Jul-Aug;101(3-4):369–404. doi: 10.1093/genetics/101.3-4.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murti J. R., Schimenti J. C. Microwave-accelerated fixation and lacZ activity staining of testicular cells in transgenic mice. Anal Biochem. 1991 Oct;198(1):92–96. doi: 10.1016/0003-2697(91)90511-q. [DOI] [PubMed] [Google Scholar]
  17. Padmore R., Cao L., Kleckner N. Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell. 1991 Sep 20;66(6):1239–1256. doi: 10.1016/0092-8674(91)90046-2. [DOI] [PubMed] [Google Scholar]
  18. Petes T. D., Hill C. W. Recombination between repeated genes in microorganisms. Annu Rev Genet. 1988;22:147–168. doi: 10.1146/annurev.ge.22.120188.001051. [DOI] [PubMed] [Google Scholar]
  19. Scherer S., Davis R. W. Recombination of dispersed repeated DNA sequences in yeast. Science. 1980 Sep 19;209(4463):1380–1384. doi: 10.1126/science.6251545. [DOI] [PubMed] [Google Scholar]
  20. Schimenti J. C., Duncan C. H. Ruminant globin gene structures suggest an evolutionary role for Alu-type repeats. Nucleic Acids Res. 1984 Feb 10;12(3):1641–1655. doi: 10.1093/nar/12.3.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smithies O., Powers P. A. Gene conversions and their relation to homologous chromosome pairing. Philos Trans R Soc Lond B Biol Sci. 1986 Jan 29;312(1154):291–302. doi: 10.1098/rstb.1986.0008. [DOI] [PubMed] [Google Scholar]
  22. Sugawara N., Szostak J. W. Recombination between sequences in nonhomologous positions. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5675–5679. doi: 10.1073/pnas.80.18.5675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Waldman A. S., Liskay R. M. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol Cell Biol. 1988 Dec;8(12):5350–5357. doi: 10.1128/mcb.8.12.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walsh J. B. Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion? Genetics. 1987 Nov;117(3):543–557. doi: 10.1093/genetics/117.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilson A. C., Bush G. L., Case S. M., King M. C. Social structuring of mammalian populations and rate of chromosomal evolution. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5061–5065. doi: 10.1073/pnas.72.12.5061. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES