Lazarus effects: the frequency and genetic causes ofEscherichia colipopulation recovery under lethal heat stress

ABSTRACT Sometimes populations crash and yet recover before being lost completely. Such recoveries have been observed incidentally in evolution experiments using Escherichia coli , and this phenomenon has been termed the “Lazarus effect.” To investigate how often recovery occurs and the genetic changes that drive it, we evolved ~300 populations of E. coli at lethally high temperatures (43.0°) for five days and sequenced the genomes of recovered populations. Our results revealed that the Lazarus effect is uncommon, but frequent enough, at ~9% of populations, to be a potent source of evolutionary innovation. Population sequencing uncovered a set of mutations adaptive to lethal 43.0°C that were mostly distinct from those that were beneficial at a high but nonlethal temperature (42.2°). Mutations within two operons—the heat shock hslUV operon and the RNA polymerase rpoBC operon—drove adaptation to lethal temperature. Mutations in hslUV exhibited little antagonistic pleiotropy at 37.0°C and may have arisen neutrally prior to subjection to lethal temperature. In contrast, rpoBC mutations provided greater fitness benefits than hslUV mutants, but were less prevalent and caused stronger fitness tradeoffs at lower temperatures. Recovered populations fixed mutations in only one operon or the other, but not both, indicating that epistatic interactions between beneficial mutations were important even at the earliest stages of adaptation.