A Test of the Coordinated Expression Hypothesis for the Origin and Maintenance of the GAL Cluster in Yeast

Gregory I Lang,David Botstein,Laura N Rusche

doi:10.1371/journal.pone.0025290

Abstract

Metabolic gene clusters—functionally related and physically clustered genes—are a common feature of some eukaryotic genomes. Two hypotheses have been advanced to explain the origin and maintenance of metabolic gene clusters: coordinated gene expression and genetic linkage. Here we test the hypothesis that selection for coordinated gene expression underlies the clustering of GAL genes in the yeast genome. We find that, although clustering coordinates the expression of GAL1 and GAL10, disrupting the GAL cluster does not impair fitness, suggesting that other mechanisms, such as genetic linkage, drive the origin and maintenance metabolic gene clusters.

Highlights

In eukaryotic genomes functionally related genes are, to a first approximation, dispersed throughout the genome
To determine whether the GAL cluster organization improves coordinated expression of the GAL genes, we generated diploid strains in which GFP is fused to GAL1 and mCherry is fused to GAL10 in either the cis or trans conformation (Figure 2)
Why would genetic linkage of GAL1, GAL10, and GAL7 be selectively advantageous? In S. kudriavzevii, a closely related species to S. cerevisiae, the GAL cluster, as well as the unlinked GAL2, GAL4, and GAL80 exist as degenerate pseudogenes that are maintained, along with functional alleles of these genes, despite historical gene flow between the Gal+ and Gal- subpopulations [20]

Summary

Introduction

In eukaryotic genomes functionally related genes are, to a first approximation, dispersed throughout the genome. The GAL cluster evolved independently through gene relocation in two fungal phyla (Ascomycota and Basidiomycota) and has been horizontally transferred within Ascomycota [6]. It is not clear what evolutionary forces favored the formation and maintenance of gene clusters. The physical proximity of functionally related genes could reflect selection for genetic linkage, either to maintain alleles of co-adapted genes or as a result of recurrent horizontal transfer of the gene cluster. Neither of these models has been tested experimentally. Using the GAL cluster in S. cerevisiae, we directly test the coordinated expression hypothesis, which makes two experimental predictions: (1) clustering contributes to coordination gene expression and (2) clustering provides a fitness advantage

Methods

Results

Conclusion