Heterologous Hsp90 promotes phenotypic diversity through network evolution

Abstract

Biological processes in living cells are often carried out by gene networks in which signals and reactions are integrated through network hubs. Despite their functional importance, it remains unclear to what extent network hubs are evolvable and how alterations impact long-term evolution. We investigated these issues using heat shock protein 90 (Hsp90), a central hub of proteostasis networks. When native Hsp90 in Saccharomyces cerevisiae cells was replaced by the ortholog from hypersaline-tolerant Yarrowia lipolytica that diverged from S. cerevisiae about 270 million years ago, the cells exhibited improved growth in hypersaline environments but compromised growth in others, indicating functional divergence in Hsp90 between the two yeasts. Laboratory evolution shows that evolved Y. lipolytica-HSP90–carrying S. cerevisiae cells exhibit a wider range of phenotypic variation than cells carrying native Hsp90. Identified beneficial mutations are involved in multiple pathways and are often pleiotropic. Our results show that cells adapt to a heterologous Hsp90 by modifying different subnetworks, facilitating the evolution of phenotypic diversity inaccessible to wild-type cells.

Subsets of NLR genes show differential signatures of adaptation during colonization of new habitats

“…We hypothesize that, within S. chilense , each NRC coevolves as a helper NLR with a specific set of sensor NLRs. In experimental evolution in yeast, major evolutionary and functional novelty has been shown to occur by changes in the hubs of a gene network (Koubkova‐Yu et al ., ). The main genes underlying habitat adaptation are often ‘helpers’ and do not on their own provide a specific recognition of the newly encountered pathogens (new species or genera) but improve signalling processes.…”

Genome-wide variation and transcriptional changes in diverse developmental processes underlie the rapid evolution of seasonal adaptation

“…Thus, although evolved differences are polygenic, with no particular gene having a major effect, the rapid evolution of phenology in R. pomonella appears to have favored changes in transcription at loci with higher network conductivity than expected by chance. Recent work indeed predicts that the evolution of hub-like genes can facilitate rapid evolution by facilitating larger “jumps” in phenotypic space ( 39 , 68 ). However, the generality of this result may depend on the strength of natural selection.…”

An HSP90-regulated reduced-eye phenotype in Tribolium shows fitness benefits and thus provides evidence for evolutionary capacitance

“…Chen et al (Chen et al, 2012) demonstrated that inhibiting HSP90 can potentiate fast adaptation to cytotoxic compounds by inducing aneuploidy. Very recently, Koubkova-Yu et al (Koubkova-Yu et al, 2018) found that by replacing the native HSP90 in Saccharomyces cerevisiae cells with the ortholog from hypersaline-tolerant Yarrowia lipolytica , the evolved clones showed a wider range of phenotypic variation than cells carrying native HSP90 and some of them exhibited beneficial mutations with a higher fitness improvement.…”

“…HSP90 reduction has also been suggested to lead to transposon activation, thereby generating new genetic variation (Specchia et al, 2010). Only very few studies have so far addressed the potential adaptive value of HSP90-regulated phenotypes (Chen et al, 2012; Koubkova-Yu et al, 2018; Queitsch et al, 2002; Rohner et al, 2013). For example, in surface populations of cavefish Astyanax mexicanus , HSP90 inhibition induced variation in eye size, suggesting that the evolution of adaptive eye loss in the dark might have been facilitated by HSP90 in nature (Rohner et al, 2013).…”