An Evolutionarily Conserved Prion-like Element Converts Wild Fungi from Metabolic Specialists to Generalists

Abstract

SUMMARY [GAR+] is a protein-based element of inheritance that allows yeast (Saccharomyces cerevisiae) to circumvent a normal hallmark of their biology: extreme metabolic specialization for glucose fermentation. When glucose is present, even in trace quantities, yeast will not use other carbon sources. [GAR+] allows cells to circumvent this “glucose repression.” [GAR+] is induced in yeast by a factor secreted by bacteria inhabiting their environment. We report that the de novo rates of [GAR+] appearance correlate with the yeast’s ecological niche. Evolutionarily distant fungi possess similar epigenetic elements that are also induced by bacteria. As expected for a mechanism whose adaptive value originates from the selective pressures of life in biological communities, the ability of bacteria to induce [GAR+] and the ability of yeast to respond to bacterial signals have been extinguished repeatedly during the extended monoculture of domestication. Thus, [GAR+] is a broadly conserved adaptive strategy that links environmental and social cues to heritable changes in metabolism.

Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits

“…Instead it can be heritably eliminated with transient inhibition of Hsp70, such as by expressing a dominant negative variant (Ssa1-K69M – hereafter Hsp70 DN ) (Brown and Lindquist, 2009; Jarosz et al, 2014b). We transformed strains harboring the remaining 35 Hsp104-independent states with a plasmid that constitutively expressed Hsp70 DN , picked multiple transformants, and propagated them three times.…”

“…Many have argued that most prions represent pathological states (McGlinchey et al, 2011; Nakayashiki et al, 2005). Others have suggested that fungal prions could serve as sophisticated bet-hedging devices that are beneficial in stressful environments (Griswold and Masel, 2009; Halfmann et al, 2012; Jarosz et al, 2014b; True and Lindquist, 2000). Most phenotypic states we identified were benign in rich medium and beneficial in the conditions we used to isolate them.…”

The Role of Functional Prion-Like Proteins in the Persistence of Memory

“…2). Recent identification of new functional prion-like proteins in various organisms, including human, supports the idea that nonpathogenic prions may perform a wide range of biologically meaningful roles (Coustou et al 1997;Eaglestone et al 1999;True and Lindquist 2000;Ishimaru et al 2003;True et al 2004;Hou et al 2011;Jarosz et al 2014).…”

Monoculture Breeds Poor Social Skills

“…Indeed, Jarosz et al (2014b) report the existence of genetic mimics of [GAR + ] in several wild strains isolated from soils, and as expected, the defining genetic features of prion-based inheritance are missing in this group. However, this metastable existence is a characteristic of all yeast prions and, in some cases, may provide the host organism with advantageous bet-hedging functions (Halfman and Lindquist, 2010).…”

“…The resulting bacterial spoilage of the highly valued byproduct of yeast metabolism is typically assumed to be a consequence of the failure of the yeast to produce enough ethanol to give it a growth advantage over the bacteria also found in grape must. Now, two papers in this issue from the Lindquist and Bisson laboratories (Jarosz et al, 2014a(Jarosz et al, , 2014b indicate that, in fact, the ''spoiling'' bacteria trigger, rather than passively capitalize on, the arrest in yeast fermentation by secreting a yet-tobe identified chemical messenger that induces the appearance in the wine yeast of a protein-based epigenetic determinant called [GAR + ] (Figure 1). This chemical dialog with the bacteria is not limited to wine yeasts either but is observed with multiple fruit yeasts and brewing yeasts.…”