MtDNA

Mitochondrial DNA (mtDNA) is the small, circular genome located in mitochondria, the energy-producing organelles of the cell. In humans and most animals, the mitochondrial genome is about 16,569 base pairs long and contains 37 genes: 13 protein-coding genes involved in oxidative phosphorylation, 22 transfer RNAs, and 2 ribosomal RNAs. mtDNA is present in many copies per cell, varies by tissue, and is inherited maternally. It lacks introns and is typically inherited as a single, non-recombined lineage in most individuals.

Inheritance and evolution: mtDNA is transmitted from mother to offspring with rare exceptions of paternal leakage and is effectively non-recombining, making it a useful tool for tracing maternal lineages and studying population history. Mutation rates in mtDNA are relatively high compared with nuclear DNA, leading to distinct haplogroups that reflect ancient maternal ancestry.

Genetics and function: The 13 protein-coding mtDNA genes encode components of the electron transport chain and ATP synthase, while the 22 tRNAs and 2 rRNAs enable mitochondrial translation. Transcription is driven by mitochondrial promoters and regulated by nuclear-encoded factors such as TFAM. Replication of mtDNA is carried out by DNA polymerase gamma and associated components.

Applications and clinical relevance: mtDNA is used in forensic science, anthropology, and ancient DNA studies, as well as in population genetics. Pathogenic mtDNA mutations can cause mitochondrial diseases, often through heteroplasmy, where mutant and normal genomes coexist; disease severity depends on the proportion of mutant genomes. Notable disorders include Leber hereditary optic neuropathy (LHON) and MELAS.

Limitations and caveats: mtDNA analysis can be confounded by NUMTs—nuclear copies of mitochondrial DNA. Although the non-recombining nature simplifies some phylogenetic inferences, it can limit detection of recombination events. Variation in copy number among tissues and samples can affect interpretation.