中央研究院 資訊科學研究所

NUMTs (Nuclear mtDNA), are partial copies of the mitochondrial genome found in the nuclear genome. They are sometimes referred to as molecular fossils, and, due to the higher mutation rate of mtDNA, can in some cases be more similar to parts of our ancestral mtDNA than our extent mtDNA genome is.

The existence of NUMTs has been known for decades and many informatics studies on NUMTs have attempted to elucidate the characteristics of their insertion sites. By showing that NUMTs are typically very clean insertions with only minimal deletion or duplication of the surrounding nuclear DNA, these studies have lead to a consensus opinion that most NUMTs are likely inserted as filler DNA via NHEJ (Non-Homologous End Joining).

Previous informatics studies have not shed much light upon the preferred insertion sites of NUMTs. Most of them conclude that NUMT insertion is random -- except for contradictory reports that NUMTs correlate positively, or negatively, with retrotransposons. Fortunately, by employing more careful methodology, we were able to discover several as yet undiscovered aspects of this phenomenon.

We found that inferred NUMTs insertion sites strongly correlate with predicted physical properties of DNA (curvature and bendability) and A+T rich oligomers. Moreover, recently inserted NUMTs correlate strongly with nucleosome free regions as measured by DNase-seq and FAIRE-seq. We also firmly establishing that NUMTs do indeed tend to co-occur with retrotransposons. As for the source mtDNA which is copied to create NUMTs, we find that part of the mtDNA D-loop region is very seldom copied.

Relating these facts to concrete hypotheses regarding the mechanism of NUMT insertion proved very challenging, but also fascinating, as it touched upon diverse topics in molecular biology: from retrotransposon activity and DNA repair to evolutionary conservation of chromatin structure and the packaging of mtDNA.

REFERENCES

Tsuji et al., doi:10.1093/nar/gks424, Nucleic Acids Research, 2012.