title: MtDNA mutation pattern in tumors and human evolution are shaped by similar selective constraints.
abstract: Multiple human mutational landscapes of normal and cancer conditions are currently available. However, while the unique mutational patterns of tumors have been extensively studied, little attention has been paid to similarities between malignant and normal conditions. Here we compared the pattern of mutations in the mitochondrial genomes (mtDNAs) of cancer (98 sequences) and natural populations (2400 sequences). De novo mtDNA mutations in cancer preferentially colocalized with ancient variants in human phylogeny. A significant portion of the cancer mutations was organized in recurrent combinations (COMs), reaching a length of seven mutations, which also colocalized with ancient variants. Thus, by analyzing similarities rather than differences in patterns of mtDNA mutations in tumor and human evolution, we discovered evidence for similar selective constraints, suggesting a functional potential for these mutations.
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Zhidkov
authors.forename: Erez A
authors.initials: EA
authors.lastname: Livneh
authors.forename: Eitan
authors.initials: E
authors.lastname: Rubin
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
mesh_terms: D005075:Biological Evolution; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm