Abstract

BackgroundResponses to extracellular stress are required for microbes to survive in changing environments. Although the stress response mechanisms have been characterized extensively, the evolution of stress response pathway remains poorly understood. Here, we studied the evolution of High Osmolarity Glycerol (HOG) pathway, one of the important osmotic stress response pathways, across 10 yeast species and underpinned the evolutionary forces acting on the pathway evolution.ResultsAlthough the HOG pathway is well conserved across the surveyed yeast species, the evolutionary rate of the genes in this pathway varied substantially among or within different lineages. The fast divergence of MSB2 gene indicates that this gene is subjected to positive selection. Moreover, transcription factors in HOG pathway tend to evolve more rapidly, but the genes in conserved MAPK cascade underwent stronger functional selection. Remarkably, the dN/dS values are negatively correlated with pathway position along HOG pathway from Sln1 (Sho1) to Hog1 for transmitting external signal into nuclear. The increased gradient of selective constraints from upstream to downstream genes suggested that the downstream genes are more pleiotropic, being required for a wider range of pathways. In addition, protein length, codon usage, gene expression, and protein interaction appear to be important factors to determine the evolution of genes in HOG pathway.ConclusionsTaken together, our results suggest that functional constraints play a large role in the evolutionary rate variation in HOG pathway, but the genetic variation was influenced by quite complicated factors, such as pathway position, protein length and so on. These findings provide some insights into how HOG pathway genes evolved rapidly for responding to environmental osmotic stress changes.ReviewersThis article was reviewed by Han Liang (nominated by Laura Landweber), Georgy Bazykin (nominated by Mikhail Gelfand) and Zhenguo Lin (nominated by John Logsdon).

Highlights

  • Responses to extracellular stress are required for microbes to survive in changing environments. the stress response mechanisms have been characterized extensively, the evolution of stress response pathway remains poorly understood

  • Taken together, our results suggest that functional constraints play a large role in the evolutionary rate variation in High Osmolarity Glycerol (HOG) pathway, but the genetic variation was influenced by quite complicated factors, such as pathway position, protein length and so on

  • These findings provide some insights into how HOG pathway genes evolved rapidly for responding to environmental osmotic stress changes

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Summary

Introduction

Responses to extracellular stress are required for microbes to survive in changing environments. The stress response mechanisms have been characterized extensively, the evolution of stress response pathway remains poorly understood. We studied the evolution of High Osmolarity Glycerol (HOG) pathway, one of the important osmotic stress response pathways, across 10 yeast species and underpinned the evolutionary forces acting on the pathway evolution. Sensing and responding to their changing environmental conditions are crucial challenges for microbes to survive in highly divergent niches they occupy [1,2]. Protein Kinase) pathway is required for adapting to osmotic stress in yeast and other eukaryotes [4,5]. The HOG pathway is greatly characterized in budding yeast Saccharomyces cerevisiae [6,7]. In response to hyperosmotic stress, Pbs becomes activated, leading to the phosphorylation and nuclear accumulation of

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