Fig. 4

Hypothetical mode of progression from normal cells to metastasis. Each circle within a cell represents wild type mtDNA (white background) carrying different mutations (colored sectors). Cells with grey mutations may be positively selected and pink mutations may start becoming selected against during tumor progression of the primary carcinoma (brown-shaded cell among the normal ones). Subsequently, cells devoid of pink mutations and homoplasmic for the grey mutation may be further selected for their metastatic potential, and they may subsequently accumulate green and black mutations (purple-shaded cells among the carcinoma ones)