Evidence for asymmetric DNA strand inheritance in vertebrate mitochondria
DOI:
https://doi.org/10.31489/2026feb3/30-42Keywords:
mitochondrial DNA, DNA strand equivalence, patterns of mutation, Chargaff’s second parity rule, DNA replicationAbstract
A classical experiment proposed in 1958 by Meselson and Stahl confirmed the semi-conservative mechanism of DNA replication in cellular organisms, according to which, after cell division, each daughter cell inherits a chromosome consisting of one parental chain (W or C) and one newly synthesized complementary chain (C' or W'). Since each DNA strand is replicated the same number of times after each cell division, it can be assumed that the W and C chains are equivalent as a result of a combination of cell division and a semi-conservative DNA replication mechanism. However, some non-cellular organisms, including single-stranded DNA and RNA viruses, do not conform to the concept of strand equivalence. A key feature of vertebrate mitochondrial genomes is the notable asymmetry in nucleotide composition between their two chains. This allows them to be separated during ultracentrifugation in an alkaline cesium chloride gradient into a heavy (H) chain that is rich in guanine and thymine, and a light (L) strand enriched in cytosine and adenine nucleotides. Despite extensive research, the exact mechanism of human mitochondrial DNA replication and its possible connection to this asymmetric composition remain unclear. In this paper, we propose a conceptual model for asymmetric inheritance of mitochondrial DNA strands to account for the strand-specific mutation asymmetry characteristic of vertebrate mtDNA.
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