The genes that encode the alpha, beta, and gamma subunits of component C of methyl coenzyme M reductase (mcrA, mcrB, and mcrG) in Methanococcus vannielii have been cloned and sequenced, and their expression in Escherichia coli has been demonstrated. These genes are organized into a five-gene cluster, mcrBDCGA, which contains two genes, designated mcrC and mcrD, with unknown functions. The mcr genes are separated by very short intergenic regions that contain multiple translation stop codons and strong ribosome binding sequences. Although the genome of M. vannielii is 69 mol % A+T, there is a very strong preference in the mcrA, mcrB, and mcrG genes for the codon with a C in the wobble position in the codon pairs AA(C/U) UU(C/U) (phenylalanine), and UA(C/U) (tyrosine). The mcrC and mcrD genes do not show this codon preference and frequently have U or A in the wobble position. As the codon pairs listed above are likely to be translated by the same tRNA with a G in the first anticodon position, the presence of C in the wobble position might ensure maximum efficiency of translation of transcripts of these very highly expressed genes.