1. Cancer Biology
  2. Evolutionary Biology

Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk

  1. Juan M Vazquez
  2. Vincent J Lynch  Is a corresponding author
  1. University of California, Berkeley, United States
  2. University at Buffalo, United States
https://doi.org/10.7554/eLife.65041
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  1. Juan M Vazquez
  2. Vincent J Lynch
(2021)
Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk
eLife 10:e65041.
https://doi.org/10.7554/eLife.65041
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Abstract

The risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Proboscideans) are a particularly interesting lineage for the exploration of mechanisms underlying the evolution of augmented cancer resistance because they evolved large bodies recently within a clade of smaller bodied species (Afrotherians). Here, we explore the contribution of gene duplication to body size and cancer risk in Afrotherians. Unexpectedly, we found that tumor suppressor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Juan M Vazquez

    Department of Integrative Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Vincent J Lynch

    Department of Biological Sciences, University at Buffalo, Buffalo, United States
    For correspondence
    vjlynch@buffalo.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5311-3824

Funding

University of Chicago

  • Juan M Vazquez
  • Vincent J Lynch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

Version history

  1. Received: November 19, 2020
  2. Accepted: January 28, 2021
  3. Accepted Manuscript published: January 29, 2021 (version 1)
  4. Version of Record published: March 11, 2021 (version 2)

Copyright

© 2021, Vazquez & Lynch

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Juan M Vazquez
  2. Vincent J Lynch
(2021)
Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk
eLife 10:e65041.
https://doi.org/10.7554/eLife.65041

Share this article

https://doi.org/10.7554/eLife.65041

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Further reading

    1. Cancer Biology
    2. Evolutionary Biology

    Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra

    Juan Manuel Vazquez, Maria T Pena ... Vincent J Lynch
    Research Advance Updated

    The risk of developing cancer is correlated with body size and lifespan within species, but there is no correlation between cancer and either body size or lifespan between species indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Previously we showed that several large bodied Afrotherian lineages evolved reduced intrinsic cancer risk, particularly elephants and their extinct relatives (Proboscideans), coincident with pervasive duplication of tumor suppressor genes (Vazquez and Lynch, 2021). Unexpectedly, we also found that Xenarthrans (sloths, armadillos, and anteaters) evolved very low intrinsic cancer risk. Here, we show that: (1) several Xenarthran lineages independently evolved large bodies, long lifespans, and reduced intrinsic cancer risk; (2) the reduced cancer risk in the stem lineages of Xenarthra and Pilosa coincided with bursts of tumor suppressor gene duplications; (3) cells from sloths proliferate extremely slowly while Xenarthran cells induce apoptosis at very low doses of DNA damaging agents; and (4) the prevalence of cancer is extremely low Xenarthrans, and cancer is nearly absent from armadillos. These data implicate the duplication of tumor suppressor genes in the evolution of remarkably large body sizes and decreased cancer risk in Xenarthrans and suggest they are a remarkably cancer-resistant group of mammals.

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    eLife is pleased to present a Special Issue to highlight recent advances in the growing and increasingly interdisciplinary field of evolutionary medicine.

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