Heritable transformation of adaptive landscapes elicited by transient expression of intrinsically disordered proteins (586.2)

Many environmental stresses elicit specific responses that promote survival. Whether such transient changes in gene expression have additional long‐term consequences is unknown. Here we examine the overexpression phenotypes of each open reading frame in the yeast genome under a diverse set of growth conditions. Over fifty proteins created an enduring change in phenotype when overexpression was stopped. The vast majority of these proteins harbor intrinsically disordered domains, and many are also regulated by environmental stress. Most of the traits produced by transient overexpression were beneficial and obeyed the non‐Mendelian patterns of inheritance typical of yeast prions. Like well‐known yeast prions, these traits critically depended on cellular protein homeostasis networks. However, unlike most other yeast prions, inheritance of these phenotypes often did not involve the formation of amyloid by the causal protein or require the protein disaggregase Hsp104. Rather, these traits depended on the protein folding activity of the Hsp70 chaperone to be transmitted from mother cells to their daughters, thus defining a new type of protein‐only inheritance. Taken together, our findings suggest that transient bursts in gene expression can heritably reshape adaptive landscapes by driving the acquisition of self‐perpetuating protein conformations.