biostudies-literatureSandberg TENNF Center for BiosustainabilityNovo Nordisk FondenNational Science Foundation107500https://www.ebi.ac.uk/biostudies/studies/S-EPMC10448532biostudies-literatureUnknown26(9)The bacterial strain JCVI-syn3.0 stands as the first example of a living organism with a minimized synthetic genome, derived from the <i>Mycoplasma mycoides</i> genome and chemically synthesized <i>in vitro</i>. Here, we report the experimental evolution of a syn3.0- derived strain. Ten independent replicates were evolved for several hundred generations, leading to growth rate improvements of > 15%. Endpoint strains possessed an average of 8 mutations composed of indels and SNPs, with a pronounced C/G- > A/T transversion bias. Multiple genes were repeated mutational targets across the independent lineages, including phase variable lipoprotein activation, 5 distinct; nonsynonymous substitutions in the same membrane transporter protein, and inactivation of an uncharacterized gene. TranscriptiScienceAdaptive evolution of a minimal organism with a synthetic genome.PMC10448532Biofoundry and Strain Design TeamsNNF10CC1016517MCB 1840320MCB 1818344MCB 2221237MCB 1840301Glass JIWise KSDalldorf CPalsson BOSzubin RSandberg TEFeist AMfalseAdaptive evolution of a minimal organism with a synthetic genome.The bacterial strain JCVI-syn3.0 stands as the first example of a living organism with a minimized synthetic genome, derived from the <i>Mycoplasma mycoides</i> genome and chemically synthesized <i>in vitro</i>. Here, we report the experimental evolution of a syn3.0- derived strain. Ten independent replicates were evolved for several hundred generations, leading to growth rate improvements of > 15%. Endpoint strains possessed an average of 8 mutations composed of indels and SNPs, with a pronounced C/G- > A/T transversion bias. Multiple genes were repeated mutational targets across the independent lineages, including phase variable lipoprotein activation, 5 distinct; nonsynonymous substitutions in the same membrane transporter protein, and inactivation of an uncharacterized gene. Transcript2023-01-01T00:00:00Z2023 Sep2026-04-08T12:38:55.853Z2025-04-21T15:02:35.052ZS-EPMC104485323763603810.1016/j.isci.2023.107500