Estimates of the fraction of nucleotide substitutions driven by positive
selection vary widely across different species. Accounting for different
estimates of positive selection has been difficult, in part because selection
on polymorphism within a species is known to obscure a signal of positive
selection between species. While methods have been developed to control for the
confounding effects of negative selection against deleterious polymorphism, the
impact of balancing selection on estimates of positive selection has not been
assessed. In Saccharomyces cerevisiae, there is no signal of positive selection
within protein coding sequences as the ratio of nonsynonymous to synonymous
polymorphism is higher than that of divergence. To investigate the impact of
balancing selection on estimates of positive selection we examined five genes
with high rates of nonsynonymous polymorphism in S. cerevisiae relative to
divergence from S. paradoxus. One of the genes, a high affinity zinc
transporter ZRT1, shows an elevated rate of synonymous polymorphism indicative
of balancing selection. The high rate of synonymous polymorphism coincides with
nonsynonymous divergence between three haplotype groups, which we find to be
functionally indistinguishable. We conclude that balancing selection is not
likely to be a common cause of genes harboring a large excess of nonsynonymous
polymorphism in yeast