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, Martine Bèrubè, Nader Pourmand, Tomas Marques-Bonet, Mary J. O'Connell, Per J. Palsbøll, Carlo C. Maley, Beth Shapiro

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Cetaceans are a clade of highly specialized aquatic mammals that include the largest animals that have ever lived. The largest whales can have ∼1,000× 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 ten 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 interocean 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.

Original languageEnglish (US)
Pages (from-to)1746-1763
Number of pages18
JournalMolecular biology and evolution
Volume36
Issue number8
DOIs
StatePublished - Aug 1 2019

Keywords

  • Cancer
  • Cetaceans
  • Evolution
  • Genome
  • Humpback whale

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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