Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct:165:49-55.
doi: 10.1016/j.pbiomolbio.2021.08.002. Epub 2021 Aug 8.

Reverting to single-cell biology: The predictions of the atavism theory of cancer

Kimberly J Bussey  1 , Paul C W Davies  2
Affiliations

Reverting to single-cell biology: The predictions of the atavism theory of cancer

Kimberly J Bussey et al. Prog Biophys Mol Biol. 2021 Oct.

Abstract

Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate - a well-known hallmark of cancer - is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.

Keywords: Atavism; Bacteria; Evolutionary ages; Phylostratigraphy; SOS response; Unicellularity.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could be perceived to have influenced the work reported in this paper.

References

    1. Akdemir KC, Le VT, Kim JM, Killcoyne S, King DA, Lin Y-P, Tian Y, Inoue A, Amin SB, Robinson FS, Nimmakayalu M, Herrera RE, Lynn EJ, Chan K, Seth S, Klimczak LJ, Gerstung M, Gordenin DA, O'Brien J, Li L, Deribe YL, Verhaak RG, Campbell PJ, Fitzgerald R, Morrison AJ, Dixon JR, Andrew Futreal P, 2020. Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure. Nat. Genet 52, 1178–1188. 10.1038/s41588-020-0708-0. - DOI - PMC - PubMed
    1. Aktipis CA, Boddy AM, Jansen G, Hibner U, Hochberg ME, Maley CC, Wilkinson GS, 2015. Cancer across the tree of life: cooperation and cheating in multicellularity. Phil. Trans. R. Soc. B 370, 20140219. 10.1098/rstb.2014.0219. - DOI - PMC - PubMed
    1. Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DTW, Kool M, Zapatka M, Northcott PA, Sturm D, Wang W, Radlwimmer B, Højfeldt JW, Truffaux N, Castel D, Schubert S, Ryzhova M, Şeker-Cin H, Gronych J, Johann PD, Stark S, Meyer J, Milde T, Schuhmann M, Ebinger M, Monoranu C-M, Ponnuswami A, Chen S, Jones C, Witt O, Collins VP, von Deimling A, Jabado N, Puget S, Grill J, Helin K, Korshunov A, Lichter P, Monje M, Plass C, Cho Y-J, Pfister SM, 2013. Reduced H3K27me3 and DNA hypo-methylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cane. Cell 24, 660–672. 10.1016/j.ccr.2013.10.006. - DOI - PubMed
    1. Biernaux C, Loos M, Sels A, Huez G, Stryckmans P, 1995. Detection of major bcrabl gene expression at a very low level in blood cells of some healthy individuals. Blood 86, 3118–3122. - PubMed
    1. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV, 1998. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood 92, 3362–3367. - PubMed

Publication types