Writing in Nature, Moger-Reischer et al.1 address this question by studying minimal cells from the Mycoplasma mycoides JCVI-syn3B strain. First, they test how reducing protein coding genes from the approximately 900 found in the original strain (non-minimal cell) to less than 500 in the streamlined strain (minimal cell) affects mutation input. Surprisingly, both strains display similar mutation rates and mutational spectra, indicating that reducing the genome in the minimal cells does not increase viable mutations. It is worth noting though that the minimal cells exhibit increased AT bias in single-nucleotide mutations, the predominant category of mutations in both strains.
But how is cellular fitness affected? To answer this the authors serially passaged both strains for 2000 generations. Given the observed mutational rates, any evolutionary divergence in the two strains during this period would reflect changes in genomic composition rather than side effects of synthetic streamlining. The authors observe that minimal cells initially face a steep cost, exhibiting halved maximum growth rate and fitness. However, they swiftly recover, adapting faster than their unmodified counterparts. Remarkably, by analyzing nonsynonymous mutations at shared essential genes, the authors show that minimal and non-minimal cells accumulate beneficial mutations at divergent sets of essential genes, suggesting that their mutational trajectories are different and that positive selection acts differently on the two strains. Furthermore, the differences in mutation acquisition between essential and non-essential genes in the non-minimal cell are not significant, indicating that mutations in the essential genes do not steer the evolutionary wheel on their own.
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