title: ZRT1 Harbors an Excess of Nonsynonymous Polymorphism and Shows Evidence of Balancing Selection in Saccharomyces cerevisiae.
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 among 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, the high-affinity zinc transporter ZRT1 showed an elevated rate of synonymous polymorphism indicative of balancing selection. The high rate of synonymous polymorphism coincided with nonsynonymous divergence among three haplotype groups, among which we found no detectable differences in ZRT1 function. Our results implicate balancing selection in one of five genes exhibiting a large excess of nonsynonymous polymorphism in yeast. We conclude that balancing selection is a potentially important factor in estimating the frequency of positive selection across the yeast genome.
authors.affiliation: Molecular Genetics and Genomics Program, Washington University, St. Louis, Missouri 63108.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Engle
authors.affiliation: Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University, St. Louis, Missouri 63108 jfay@genetics.wustl.edu.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Fay
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D009711:Nucleotides; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D027682:Cation Transport Proteins; D009711:Nucleotides; D029701:Saccharomyces cerevisiae Proteins; C098750:ZRT1 protein, S cerevisiae
keywords: McDonald-Kreitman test; balancing selection; yeast; zinc
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