Inter-laboratory evolution of a model organism and its epistatic effects on mutagenesis screens

In theory, a few naturally occurring evolutionary changes in the genome of a model organism may have little or no observable impact on its wild type phenotype, and yet still substantially impact the phenotypes of mutant strains through epistasis. To see if this is happening in a model organism, we obtained nine different laboratories’ wild type Myxococcus xanthus DK1622 “sublines” and sequenced each to determine if they had evolved after their physical separation. Under a common garden experiment, each subline satisfied the phenotypic prerequisites for wild type, but many differed to a significant degree in each of the four quantitative phenotypic traits we measured, with some sublines differing by several-fold. Genome resequencing identified 29 variants between the nine sublines, and eight had at least one unique variant within an Open Reading Frame (ORF). By disrupting the ORF MXAN7041 in two different sublines, we demonstrated substantial epistasis from these naturally occurring variants. The impact of such inter-laboratory wild type evolution is important to any genotype-to-phenotype study; an organism’s phenotype may be sensitive to small changes in genetic background, so that results from phenotypic screens and other related experiments might not agree with prior published results or the results from other laboratories.