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Published January 1993 | Published
Journal Article Open

Forbidden Synonymous Substitutions in Coding Regions

Abstract

In the evolution of highly conserved genes, a few "synonymous" substitutions at third bases that would not alter the protein sequence are forbidden or very rare, presumably as a result of functional requirements of the gene or the messenger RNA. Another 10% or 20% of codons are significantly less variable by synonymous substitution than are the majority of codons. The changes that occur at the majority of third bases are subject to codon usage restrictions. These usage restrictions control sequence similarities between very distant genes. For example, 70% of third bases are identical in calmodulin genes of man and trypanosome. Third-base similarities of distant genes for conserved proteins are mathematically predicted, on the basis of the G+C composition of third bases. These observations indicate the need for reexamination of methods used to calculate synonymous substitutions.

Additional Information

© 1993 The University of Chicago. Received June 22, 1992; revision received July 27, 1992; Accepted July 27, 1992. Masatoshi Nei, reviewing editor. I wish to thank Eric H. Davidson, Temple F. Smith, and Tim Hunkapiller. The work was partially supported by ONR and NIH grants.

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August 20, 2023
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