Genetic Code of Mitochondria

The genetic code of mitochondria is not the same as the universal code, which has implications for the evolution of mitochondria. Human mitochondria contain a set of tRNA molecules that are not found elsewhere in the 

First Position (5 end) Second Position Third Position (3 end) 

AGA and AGG are termination codons rather than codons for arginine. 

AUA and AUU are initiation codons, as is AUG. Both AUA and AUG also code for methionine. AUU also codes for isoleucine, as in the universal code. 

AUA codes for methionine (and initiation, as shown in item 3) instead of isoleucine. 

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Variations in the genetic code in mitochondria support the idea of their existence as free-living bacteria early in evolutionary history. 

Table 12.1. The genetic code presented in this table is very nearly universal. There are isolated exceptions in the genome of mitochondria, which is described later in this chapter. Beyond that, the genetic code has been expanded to include codons for two unusual amino acids that occur in a modest number of proteins. These amino acids are selenomethionine, in which an atom of selenium replaces the sulfur atom of methionine, and pyrrolysine, a cychzed form of lysine. For details, see A. Ambrogelly, S. Palioura, and D. Soil, Nat Chem Biol 3 29-35 (2007). 

As the genetic code provides 4 = 64 codons for the 20 amino acids, there are several synonymous codons for most amino acids— the code is degenerate. Three triplets do not code for amino acids, but instead signal the end of translation (stop codons). Another special codon, the start codon, marks the start of translation. The code shown here is almost universally applicable only the mitochondria (see p. 210) and a few microorganisms deviate from it slightly. 

Mitochondria contain the only extranuclear genomic DNA (mtDNA) and it encodes 13 proteins using a genetic code different from that in the nucleus. These proteins are key components of OXPHOS I, III, IV and V, but not complex II, which is solely encoded by nuclear DNA (nuDNA). Inhibition of mtDNA transcription as well as expression of mitochondrial proteins will therefore lead to loss of OXPHOS function. Probably the best known drugs that inhibit mtDNA synthesis are the nucleotide... 

C, G or T. This is not sufficient to encode the 20 possible amino acids. In triplets of 3 positions, there are 64 possible combinations. Hence, the system uses triplets, called codons. The code for each protein starts with an ATG (start codon) and ends with a TAA, TAG or a TGA (stop codons). The code is almost universal only mitochondria and ciliated protozoa have a different genetic code. 

Of the very few variations in the genetic code that we know of, most occur in mitochondrial DNA (mtDNA), which encodes only 10 to 20 proteins. Mitochondria have their own tRNAs, so their code variations do not affect the much larger cellular genome. 

Universality The genetic code is virtually universal, that is, the specificity of the genetic code has been conserved from very early stages of evolution, with only slight differences in the manner in which the code is translated. [Note An exception occurs in mitochondria, in which a few codons have different meanings than those shown in Figure 31.2.]... 

Many of the known variations in the genetic code are found in genes of mitochondria and chloroplasts. It is easy to see why these genetic systems might be more plastic, since they frequently encode only 10-20 proteins. The remainder of the organellar proteins are derived by importing nuclear gene products. 

Bessho, Y., Ohama, T. and Osawa, S. (1 992) Planarian mitochondria, ii. The unique genetic code as deduced from cytochrome c oxidase subunit 1 gene sequences. journal of Molecular Evolution 34, 331-335. 

Ohama, T., Osawa, S., Watanabe, K. and Jukes, T.H. (1990) Evolution of the mitochondrial genetic code. IV. AAA as an asparagine codon in some animal mitochondria. Journal of Molecular Evolution 30, 329-332. 

The genetic code is not universal but is the same in most organisms. Exceptions are found in mitochondrial genomes where some codons specify different amino acids to that normally encoded by nuclear genes. In mitochondria, the UGA codon does not specify termination of translation but instead encodes for tryptophan. Similarly, in certain protozoa UAA and UAG encode glutamic acid instead of acting as termination codons. 

Mitochondria of various organisms use different genetic code. Search the Internet site to obtain information for the mitochondrial codons from either vertebrates or invertebrates. Discuss usage differences between the standard codons and mitochondrial codons. 

The broad outlines of eukaryotic protein synthesis are the same as in prokaryotic protein synthesis. The genetic code is generally the same (some microorganisms and eukaryotic mitochondria use slightly different codons), rRNA and protein sequences are recognizably similar, and the same set of amino acids is used in all organisms. However, specific differences exist between the two types of protein synthesis at all steps of the process. 

In mammalian cells, some 1% of the total cellular DNA is found in the mitochondria. This DNA is double stranded, circular, and small, with a molecular weight of about 10 million, which is in the same range as that of viral DNAs. Some four to ten molecules of DNA per mitochondrion, along with some ribosomes, are found in the matrix space. DNA replication, transcription, and synthesis of some mitochondrial proteins take place in the matrix space. This protein synthesis very much resembles that of bacteria. The mitochondrial genetic code differs from the "universal" genetic code (Chapter 12) used for nuclearly encoded proteins and bacteria. The reasons for this are unknown. 

The code appears to be universal to the extent that synthetic polyribonucleotides seem to code in the same way in mammals, bacteria, and other species, and components of the protein-synthesizing system of various species can operate with components from certain others. Mitochondria and ciliated protozoa have genetic codes slightly different from the standard. For example, in human mitochondria, UGA codes for tryptophan instead of as a termination signal, AUA codes for methionine rather than isoleucine, and AGA and AGG are termination signals rather than coding for arginine. 

The genetic code dictionary was originally established from studies on the bacterium E. coli. It is now known to be the same for all organisms i.e., it is universal. The only exceptions occur for a few codons in mitochondria from a number of species. 

For some considerable time, it was thought that the genetic code was universal, especially because genetic-engineering experiments showed repeatedly that eukaryotic genes could be expressed in bacteria such as E. coli. More recently, however, it has been found that mitochondria have their own genetic code and protein-synthetic machinery. This has led to discussions about the evolutionary origin of mitochondria, a topic that cannot be pursued here. 

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