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MBE Advance Access published online on May 3, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl003
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted April 27, 2006

Research Article

Vertebrate DNA Transposon as a Natural Mutator: The Medaka Fish Tol2 Element Contributes to Genetic Variation without Recognizable Traces

Akihiko Koga 1 *, Atsuo Iida 1, Hiroshi Hori 1, Atsuko Shimada 2, and Akihiro Shima 3

1 Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
2 Department of Biological Sciences, Graduate School of Sciences, University of Tokyo, Tokyo 113-0033, Japan
3 Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8562, Japan; Present address: Institute for Environmental Sciences, Rokkasho, Aomori 039-3212, Japan

* To whom correspondence should be addressed.
Akihiko Koga, E-mail: koga{at}bio.nagoya-u.ac.jp


  Abstract

DNA-based transposable elements, or DNA transposons, transpose in a cut-and-paste fashion, involving excision from the chromosome. If this process affects the function of a host gene, and the excision rate is high, any gene associated with such an element would clearly be in a genetically "unstable" state, and there are many examples of unstable genes in various organisms. However, none have hitherto been reported in vertebrates. We here document the finding of an unstable mutant gene in the medaka fish Oryzias latipes, a useful model animal for vertebrate genetics and evolutionary studies. In an inbred strain, excision of the Tol2 element inserted in a pigmentation gene occurs spontaneously, giving rise to different heritable phenotypes, and new mutant genes which carry different excision footprint sequences. The phenotypic mutation rate is as high as 2% per gamete, representing a 1,000-fold increase from spontaneous mutation rates so far determined with the same organism. With mutations caused by insertion, and then excision, of transposons, one can no longer recognize participation of transposons in their generation. Thus, the impact of DNA transposons on vertebrate genomes may be, and may have been, larger than commonly supposed.

Keywords: DNA transposon; vertebrate; medaka; unstable mutation; genetic variation; genome evolution.
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