PerspectiveCell Biology

New Roles for Codon Usage

Science  17 Sep 2010:
Vol. 329, Issue 5998, pp. 1473-1474
DOI: 10.1126/science.1195567

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Summary

How do two proteins with almost indistinguishable amino acid sequences have different functions in the cell? A single amino acid change can dictate a property as complex as the topology of a membrane protein (1), but other examples are less easy to explain. One such puzzle relates to the mammalian cytoskeletal proteins β- and γ-actin, whose amino acid sequences are 98% identical. β-Actin is modified by the addition of arginine, whereas γ-actin is not, resulting in distinct roles for each in the cell. Identifying what exactly distinguishes β- from γ-actin has proved perplexing because the marginal differences in their amino-terminal sequences are not sufficient to explain why one is modified and the other is not. On page 1534 of this issue, Zhang et al. (2) show that the modification of β- and γ-actin is dictated by the codons—the triplets of nucleic acids that encode amino acids— rather than the specific amino acids themselves in the amino termini of these proteins. This is an unexpected example of proteins whose properties are determined at the nucleotide rather than the amino acid level, forcing a reassessment of what defines a synonymous change in a gene sequence.