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The Mitochondrial Palindrome Scaffold and Architectural Domains

Stumpf, D. A.

2025-11-13 evolutionary biology
10.1101/2025.11.11.687892 bioRxiv
Show abstract

Palindromic motifs comprise 28% of human mitochondrial DNA and form evolutionarily conserved guideposts that organize a persistent structural scaffold. Complementary palindromes of three types delineate mitochondrial architectural domains (MADs) capable of self-organizing dynamic configurations. A library of 423 complementary palindromes generates millions of pairing opportunities across 53,166 human GenBank genomes, revealing a poised system that balances stability and flexibility for constrained change between guideposts. Variations in guidepost flanks distinguish human groups and their homologies to other species, indicating genetic diversity that preceded speciation. These dynamics align with Kauffmans "poised system" model, in which stability and flexibility coexist to enable evolutionary bursts of diversification. A Neo4j knowledge graph containing 173,431 nodes and 119 million relationships integrated 53,166 human and 2,000 non-human mitochondrial genomes, enabling scalable exploration of mitochondrial architecture. The resulting framework provides a foundation for future studies of mitochondrial evolution, topology, and functional organization.

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