mtDNA mutation pattern in tumors and human evolution are shaped by similar selective constraints

  1. Ilia Zhidkov1,2,
  2. Erez A. Livneh2,
  3. Eitan Rubin2,3,4 and
  4. Dan Mishmar1,2,4
  1. 1 Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
  2. 2 National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
  3. 3 Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel

    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.

    Footnotes

    | Table of Contents

    This Article

    1. Published in Advance February 10, 2009, doi: 10.1101/gr.086462.108 Genome Res. 19: 576-580 Copyright © 2009 by Cold Spring Harbor Laboratory Press

    Article Category

    Share

    Preprint Server



    Current Issue

    1. March 2024, 34 (3)
    1. Current Issue
    1. Alert me to new issues of Genome Research