GroEL/S helps purge deleterious mutations and reduce genetic diversity during adaptive protein evolution

Abstract

Chaperones are proteins that help other proteins fold. They also affect the adaptive evolution of their client proteins by buffering deleterious mutations and increasing the genetic diversity of evolving proteins. We study how the bacterial chaperone GroE (GroEL + GroES) affects the evolution of green fluorescent protein (GFP). To this end we subjected GFP to multiple rounds of mutation and selection for its color phenotype in four replicate E. coli populations, and studied its evolutionary dynamics through high-throughput sequencing and mutant engineering. We evolved GFP both under stabilizing selection for its ancestral (green) phenotype, and to directional selection for a new (cyan) phenotype. We did so both under low and high expression of the chaperone GroE. In contrast to prevailing wisdom, we observe that GroE does not just buffer but also helps purge deleterious mutations from evolving populations. In doing so, GroE helps reduce the genetic diversity of evolving populations. In addition, it causes phenotypic heterogeneity in mutants with the same genotype, potentiating their effect in some cells, and buffering it in others. Our observations show that chaperones can affect adaptive evolution through more than one mechanism. HighlightsO_LIGroE reduces genetic diversity C_LIO_LIGroE potentiates the effect of deleterious mutations C_LIO_LIGroE intensifies purifying selection and leads to higher activity of client proteins C_LI