ZRT1 harbors an excess of nonsynonymous polymorphism and shows evidence of balancing selection in Saccharomyces cerevisiae

TL;DR

This study investigates the role of balancing selection in Saccharomyces cerevisiae, finding that it explains high nonsynonymous polymorphism in ZRT1 but is unlikely to be a common factor in other genes with similar patterns.

Contribution

It provides evidence that balancing selection affects ZRT1 but is generally not responsible for excess nonsynonymous polymorphism in yeast genes.

Findings

ZRT1 shows elevated synonymous polymorphism suggestive of balancing selection.

Nonsynonymous divergence among haplotypes in ZRT1 is functionally indistinguishable.

Balancing selection is unlikely to be a widespread cause of excess nonsynonymous polymorphism in yeast.

Abstract

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.