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Return to the sea, get huge, beat cancer: an analysis of cetacean genomes including an assembly for the humpback whale (Megaptera novaeangliae)

Tollis, Marc; Robbins, Jooke; Webb, Andrew E.; Kuderna, Lukas F.K.; Caulin, Aleah F.; Garcia, Jacinda D.; Bèrubè, Martine; Pourmand, Nader; Marques-Bonet, Tomas; O'Connell, Mary J.; Palsbøll, Per J.; Maley, Carlo C.


Marc Tollis

Mary J. O'Connell

Per J. Palsbøll

Carlo C. Maley

Jooke Robbins

Andrew E. Webb

Lukas F.K. Kuderna

Aleah F. Caulin

Jacinda D. Garcia

Martine Bèrubè

Nader Pourmand

Tomas Marques-Bonet


Cetaceans are a clade of highly specialized aquatic mammals that include the largest animals that have ever lived. The largest whales can have ~1000X more cells than a human, with long lifespans, leaving them theoretically susceptible to cancer. However, large-bodied and long-lived animals do not suffer higher risks of cancer mortality than humans – an observation known as Peto’s Paradox. To investigate the genomic bases of gigantism and other cetacean adaptations, we generated a de novo genome assembly for the humpback whale (Megaptera novaeangliae) and incorporated the genomes of 10 cetacean species in a comparative analysis. We found further evidence that rorquals (family Balaenopteridae) radiated during the Miocene or earlier, and inferred that perturbations in abundance and/or the inter-ocean connectivity of North Atlantic humpback whale populations likely occurred throughout the Pleistocene. Our comparative genomic results suggest that the evolution of cetacean gigantism was accompanied by strong selection on pathways that are directly linked to cancer. Large segmental duplications in whale genomes contained genes controlling the apoptotic pathway, and genes inferred to be under accelerated evolution and positive selection in cetaceans were enriched for biological processes such as cell cycle checkpoint, cell signaling, and proliferation. We also inferred positive selection on genes controlling the mammalian appendicular and cranial skeletal elements in the cetacean lineage, which are relevant to extensive anatomical changes during cetacean evolution. Genomic analyses shed light on the molecular mechanisms underlying cetacean traits, including gigantism, and will contribute to the development of future targets for human cancer therapies.

Journal Article Type Article
Publication Date May 9, 2019
Print ISSN 0737-4038
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Keywords cetaceans; humpback whale; evolution; genome; cancer
Publisher URL
Additional Information This is a pre-copyedited, author-produced version of an article accepted for publication in Molecular Biology and Evolution following peer review. The version of record Marc Tollis, Jooke Robbins, Andrew E Webb, Lukas F K Kuderna, Aleah F Caulin, Jacinda D Garcia, Martine Bèrubè, Nader Pourmand, Tomas Marques-Bonet, Mary J O’Connell, Per J Palsbøll, Carlo C Maley, Return to the sea, get huge, beat cancer: an analysis of cetacean genomes including an assembly for the humpback whale (Megaptera novaeangliae), Molecular Biology and Evolution, , msz099 is available online at

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