chrM·hg38·16.6 kb

Mitochondrial Genome

A bacterial genome trapped inside us for two billion years, running our cells with just 37 genes, no introns, and a genetic code all its own.

Physical Properties

Length16.6 kb

Topologycircular

Genomic Features

Protein-coding genes—

Gene density—

CpG islands—

EPIC v2 probes—

Notable

Disease associations

MELAS

MERRF

Leber hereditary optic neuropathy

· Circular genome, 16,569 bp — maternally inherited

· Encodes 37 genes: 13 proteins, 22 tRNAs, 2 rRNAs

· Mutation rate ~10x higher than nuclear DNA

Genomic Architecture

Heavy (H) and Light (L) strands — Named for buoyant density. H-strand encodes 12/13 mRNAs, both rRNAs, 14/22 tRNAs. L-strand encodes ND6 and 8 tRNAs.

D-loop (Displacement loop) — ~1.1 kb non-coding control region containing origins of replication, promoters, and three conserved sequence blocks. The hypervariable segment HVS-I is used in forensic identification.

No introns — Every gene is intronless — bacterial ancestry.

Evolutionary History

Endosymbiosis — ~1.5-2 billion years ago, alpha-proteobacterium engulfed by archaeal host. Most consequential merger in the history of life.

99% gene transfer — Ancestral 3,000-5,000 gene genome reduced to 37. Remaining 13 protein-coding genes hypothesized to stay because hydrophobic membrane proteins cannot be imported post-translationally.

Deep Cuts

97% of mitochondrial proteins are nuclear-encoded — Only 13 of ~1,500 mitochondrial proteins come from mtDNA. The remaining ~1,487 are imported from the cytoplasm.

Paternal mtDNA is actively destroyed — Sperm mitochondria are tagged with ubiquitin and degraded by mitophagy. Active elimination, not passive dilution.

The pharmacogenomic time bomb — m.1555A>G (carried by ~1/500 people) creates a ribosome resembling the bacterial aminoglycoside target. One injection of gentamicin = permanent bilateral deafness.

§ Deep dive

Heavy (H) and Light (L) strandsNamed for buoyant density. H-strand encodes 12/13 mRNAs, both rRNAs, 14/22 tRNAs. L-strand encodes ND6 and 8 tRNAs.

D-loop (Displacement loop)~1.1 kb non-coding control region containing origins of replication, promoters, and three conserved sequence blocks. The hypervariable segment HVS-I is used in forensic identification.

No intronsEvery gene is intronless — bacterial ancestry.

Overlapping reading framesATP8/ATP6 overlap by 46 nucleotides. ND4L/ND4 overlap by 7. Same DNA encodes parts of two proteins in different frames.

tRNA punctuation model(Ojala, Montoya & Attardi, 1981): Entire H-strand transcribed as one polycistronic transcript. tRNA folding serves as the processing signal — one of the most elegant gene expression strategies in biology.

Strand-asymmetric replicationH-strand from OH; L-strand origin (OL) ~11,000 bp away. H-strand synthesis proceeds ~2/3 around before L-strand initiates.