@article{c26a9731244e42a9a4ad11fdcbdbebac,
title = "Return to the Sea, Get Huge, Beat Cancer: An Analysis of Cetacean Genomes Including an Assembly for the Humpback Whale (Megaptera novaeangliae)",
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.",
keywords = "Cancer, Cetaceans, Evolution, Genome, Humpback whale",
author = "Marc Tollis and Jooke Robbins and Webb, {Andrew E.} and Kuderna, {Lukas F.K.} and Caulin, {Aleah F.} and Garcia, {Jacinda D.} and Martine B{\`e}rub{\`e} and Nader Pourmand and Tomas Marques-Bonet and O'Connell, {Mary J.} and Palsb{\o}ll, {Per J.} and Maley, {Carlo C.} and Beth Shapiro",
note = "Funding Information: Field data collection was supported by the Center for Coastal Studies and conducted under NOAA research permit 16325. This work was initiated with funding from Dr. Jeffrey Pearl at UC San Fransisco. This work was supported in part by NIH (Grants U54 CA217376, U2C CA233254, P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657) as well as CDMRP Breast Cancer Research Program (Award BC132057) and the Arizona Biomedical Research Commission (Grant ADHS18-198847) to C.C.M. The findings, opinions, and recommendations expressed here are those of the authors and not necessarily those of the universities where the research was performed or the National Institutes of Health. P.J.P. would like to acknowledge funding from Stockholm University and the University of Groningen. Startup funds were provided by the School of Informatics, Computing, and Cyber Systems at Northern Arizona University (M.T.). M.J.O{\textquoteright}C. would like to thank the University of Leeds funding her 250 Great Minds University Academic Fellowship. The authors thank Wensi Hao (University of Groningen) for technical support, Andrea Cabrera (University of Groningen) for helpful conversations about mutation rates and demography, and Richard E. Green (UC Santa Cruz) for consultations regarding genome sequencing, assembly, and annotation. The authors acknowledge Research Computing at Arizona State University (http:// www.researchcomputing.asu.edu), the Advanced Research Computing resources at the University of Leeds, and the Monsoon computing cluster at Northern Arizona University (https://nau.edu/high-performance-computing/) for providing high-performance computing and storage resources that have contributed to this study. Funding Information: Field data collection was supported by the Center for Coastal Studies and conducted under NOAA research permit 16325. This work was initiated with funding from Dr. Jeffrey Pearl at UC San Fransisco. This work was supported in part by NIH (Grants U54 CA217376, U2C CA233254, P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657) as well as CDMRP Breast Cancer Research Program (Award BC132057) and the Arizona Biomedical Research Commission (Grant ADHS18-198847) to C.C.M Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.",
year = "2019",
month = aug,
day = "1",
doi = "10.1093/molbev/msz099",
language = "English (US)",
volume = "36",
pages = "1746--1763",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "8",
}