Genome minimization within living cells is a straightforward approach for understanding cell systems as a whole. Cells operated by minimal genomes can be applied as resources to study the basic architecture of cell network dynamics and metabolic fluxes, and the trial -and -error of genome reduction toward minimization is the learning process used to unravel the origins of redundancy and robustness of cell systems. This review summarizes and integrates studies on bacterial genome minimization to propose a simplified guideline for genome minimization. We also describe the ongoing history toward the yeast genome minimization. Furthermore, in light of the genome minimization guideline, as well as the fundamental differences in the genome structures between bacteria and higher eukaryotes, the current state and the challenges for the human genome minimization are described. This review hopefully will provide a tentative platform to bridge systems biology and synthetic genomics in both bacterial and eukaryotic cell biology.
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