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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)


Marc Tollis

Jooke Robbins

Andrew E. Webb

Lukas F.K. Kuderna

Aleah F. Caulin

Jacinda D. Garcia


Nader Pourmand

Tomas Marques-Bonet

Per J.

Carlo C. Maley


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.


Tollis, M., Robbins, J., Webb, A. E., Kuderna, L. F., Caulin, A. F., Garcia, J. D., …Maley, C. C. (2019). 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, 36(8), 1746-1763.

Journal Article Type Article
Acceptance Date Apr 11, 2019
Online Publication Date May 9, 2019
Publication Date Aug 1, 2019
Deposit Date Apr 15, 2019
Publicly Available Date May 9, 2020
Journal Molecular Biology and Evolution
Print ISSN 0737-4038
Electronic ISSN 1537-1719
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 36
Issue 8
Pages 1746-1763
Keywords cetaceans; humpback whale; evolution; genome; cancer
Public URL
Publisher URL


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