Biotecnologia

Copyright © 2005 by the Genetics Society of America DOI: 10.1534/genetics.104.034884

Note
On the Evolution of Codon Volatility
Jianzhi Zhang1
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109 Manuscript received August 11, 2004 Accepted for publication September 30, 2004 ABSTRACT Volatility of a codon is defined as the probability that a random point mutation in the codon generates a nonsynonymous change. It has been proposed that higher-than-expected mean codon volatility of a gene indicates that positive selection for nonsynonymous changes has acted on the gene in the recent past. I show that strong frequency-dependent selection (minority advantage) in large populations can increase codon volatility slightly, whereas directional positive selection has no effect on volatility. Factors unrelated to positive selection, such as expression-related or GC-content-related codon usage bias, also affect volatility. These and other considerations suggest that codon volatility has only limited utility for detecting positive selection at the DNA sequence level.

OSITIVE Darwinian selection at the DNA sequence level is usually assessed by comparing the number of synonymous substitutions per synonymous site (dS) and the number of nonsynonymous substitutions per nonsynonymous site (d N) from an alignment of at least two homologous protein-coding DNA sequences (Li 1997; Nei and Kumar 2000). A significantly higher d N over dS is a strong indication of positive selection (Hughes and Nei 1988). Plotkin and co-workers recently introduced a new method for detecting positive selection using just one DNA sequence, and this method is based on the concept of codon volatility (Plotkin et al. 2004). Volatility of a codon is defined as the probability that a random point mutation in this codon is nonsynonymous. Codon volatility necessarily depends on mutational patterns, such as the ratio of transitional to transversional changes. In the