The Human Mitochondrial Genetic Code

Translations: ATP6, ATP8, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, CO1, CO2, CO3, CytB.

Phe F	UUU UUC	Thr T	ACU ACC ACA ACG	Asp D	GAU GAC
Leu (1) L (UUA/G)	UUA UUG	Ala A	GCU GCC GCA GCG	Glu E	GAA GAG
Leu (2) L (CUN)	CUU CUC CUA CUG	Tyr Y	UAU UAC	Cys C	UGU UGC
Ile I	AUU * AUC	Ter	UAA UAG	Trp W	UGA UGG
Met M	AUA AUG	His H	CAU CAC	Arg R	CGU CGC CGA CGG
Val V	GUU GUC GUA GUG **	Gln Q	CAA CAG	Ser (2) S (AGU/C)	AGU AGC
Ser (1) S (UCN)	UCU UCC UCA UCG	Asn N	AAU AAC	Non-Standard Stop See note below+	AGA AGG
Pro P	CCU CCC CCA CCG	Lys K	AAA AAG	Gly G	GGU GGC GGA GGG

Note that, unlike the universal code, UGA codes for tryptophan instead of termination and AUA codes for methionine instead of isoleucine.

*AUU codes for isoleucine during elongation but can code for methionine for initiation (ND2) See Fearnley & Walker (1987) and Peabody (1989).

**GUG has been reported as a functional initiation codon (ATP6) See Dubot et al (2004) below.

⁺For thirty years AGA and AGG were considered terminators instead of coding for arginine. However, in 2010 Temperley showed that human mitochondria use only UAA and UAG stop codons. Some debate has continued, see Akabane (2014), Takeuchi (2015), and Chrzanowska-Lightowlers (2015). In Mitomap we still have these codons as STOP codons, but we are currently reviewing their status.

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Akabane, S., Ueda, T., Nierhaus, K. H. and Takeuchi, N. (2014). "Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria. PLoS Genetics 10(9):e1004616.

Anderson, S., Bankier, A.T., Barrell, B.G., de Bruijn, M.H., Coulson, A.R., Drouin, J., Eperon, I.C., Nierlich, D.P., Roe, B.A., Sanger, F., Schreier, P.H., Smith, A.J., Staden, R. and Young, I.G. (1981). "Sequence and organization of the human mitochondrial genome." Nature 290(5806):457-465.

Barrell, B.G., Anderson, S., Bankier, A.T., de Bruijn, M.H., Chen, E., Coulson, A.R., Drouin, J., Eperon, I.C., Nierlich, D.P., Roe, B.A., Sanger, F., Schreier, P.H., Smith, A.J., Staden, R. and Young, I.G. (1980). "Different pattern of codon recognition by mammalian mitochondrial tRNAs." Proceedings of the National Academy of Sciences of the United States of America 77(6):3164-3166.

Barrell, B.G., Bankier, A.T. and Drouin, J. (1979). "A different genetic code in human mitochondria." Nature 282(5735):189-194.

Chrzanowska-Lightowlers, Z. M. and Lightowlers, R. N. (2015). "Response to "Ribosome Rescue and Translation Termination at Non-standard Stop Codons by ICT1 in Mammalian Mitochondria". PLoS Genetics 11(6):e1005227.

Dubot, A., Godinot, C., Dumur, V., Sablonniere, B., Stojkovic, T., Cuisset, J. M., Vojtiskova, A., Pecina, P., Jesina, P. and Houstek, J. (2004). "GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene." Biochemical and Biophysical Research Communications 313(3):687-693.

Fearnley, I. M. and Walker, J. E. (1987). "Initiation codons in mammalian mitochondria: differences in genetic code in the organelle." Biochemistry 26(25):8247-8251.

Knight, R.D., Freeland, S.J. and Landweber, L.F. (2001). "Rewiring the keyboard: evolvability of the genetic code." Nature Reviews Genetics 2(1):49-58.

Knight, R.D., Landweber, L.F. and Yarus, M. (2001). "How mitochondria redefine the code." Journal of Molecular Evolution 53(4-5):299-313.

Peabody, D. S. (1989). "Translation initiation at non-AUG triplets in mammalian cells." Journal of Biological Chemistry 264(9):5031-5035.

Takeuchi, N. and Nierhaus, K. H. (2015). "Response to the Formal Letter of Z. Chrzanowska-Lightowlers and R. N. Lightowlers Regarding Our Article "Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria". PLoS Genetics 11(6):e1005218.

Temperley, R., Richter, R., Dennerlein, S., Lightowlers, R. N. and Chrzanowska-Lightowlers, Z. M. (2010). "Hungry codons promote frameshifting in human mitochondrial ribosomes." Science 327(5963):301.

Yokobori, S., Suzuki, T. and Watanabe, K. (2001). "Genetic code variations in mitochondria: tRNA as a major determinant of genetic code plasticity." Journal of Molecular Evolution 53(4-5):314-326.