ABSTRACT
The “theory of resistant biomolecules” posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS).
First, we confirmed that guanine-quadruplex (GQ) and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with GQ motifs.
Surprisingly, even though DR, MR and GQ motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS and these results remained stable even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons.
Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Mail: Kamil.pabis{at}gmail.com
ABBREVIATIONS
- BPs
- mtDNA deletion break points
- DR
- direct repeats
- ER
- everted repeats
- GQ
- guanine-quadruplexes
- IR
- inverted repeats
- MLS
- species maximum lifespan
- MR
- mirror repeats
- nBMST
- non-B DNA motif search tool
- Nc
- number of effective codons
- PGLS
- phylogenetic generalized least squares
- SD
- standard deviation
- Trip
- Triplex forming motif
- XR
- any repeat half-site or motif
- mtDNA
- mitochondrial DNA