A <i>CDKN2C</i> retroduplication in Bowhead whales is associated with the evolution of extremely long lifespans and alerted cell cycle dynamics

Vazquez, Juan Manuel; Kraft, Morgan; Lynch, Vincent J.

doi:10.1101/2022.09.07.506958

Cited by 2 publications

References 138 publications

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Cetacean Evolution: Copulatory and Birthing Consequences of Pelvic and Hindlimb Reduction

Cooper,

Suydam,

Thewissen

2023

Sex in Cetaceans

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The earliest fossil cetaceans (archaeocetes) dramatically shifted the shape and articulation of the pelvis and hindlimbs during the land-to-sea transition. Archaeocetes were mostly semi-aquatic “walking whales” that used powerful hindlimbs to walk on land and swim to reach new aquatic sources of food. However, skeletons of the latest diverging lineages of archaeocetes, the basilosaurids, showed that the pelvis initially lost articulation with the sacrum, and hindlimbs were reduced and encased within the body wall. Consequently, basilosaurids were no longer able to bear their weight on land and probably had a different mating strategy compared to the other archaeocetes. Basilosaurid mating behaviors were probably consistent with those of modern cetaceans, including lateral- and ventral-facing copulation. Moreover, a pelvic girdle that was no longer constrained by vertebral and limb attachments likely freed fetal development from size constraints at birth, allowing for the birth of large fetuses. This study reports new data showing growth of the pelvis with age in modern bowhead whales (Balaena mysticetus) and their implications for left-right asymmetry and sex difference in pelvic dimensions among modern cetaceans. Reproductive structures present in modern cetaceans and artiodactyls were probably present in archaeocetes, including pelvic attachment of muscles associated with erection and mobility of the penis, the ischiocavernosus, in males and the clitoris of females. Within females, transverse folds along the vaginal canal are present in some terrestrial artiodactyls, modern cetaceans, and probably archaeocetes. Vaginal folds were probably exapted to assist in successful aquatic copulation in all fossil and modern cetaceans as they may protect some sperm from the lethal effects of sea water. Taken together, shifts in the pelvic girdle of cetaceans occurred over 40 million years ago and probably required changes in mating behaviors that were consistent with those seen in modern cetaceans.

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Cetacean Evolution: Copulatory and Birthing Consequences of Pelvic and Hindlimb Reduction

Cooper,

Suydam,

Thewissen

2023

Sex in Cetaceans

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DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale

Firsanov

Zacher

Xia

et al. 2023

Preprint

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At over 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg. In spite of its very large number of cells, the bowhead is not highly cancer-prone, an incongruity termed Peto's Paradox. This has been explained by the evolution of additional tumor suppressor genes in larger animals, which is supported by research on elephants demonstrating expansion of the p53 gene. However, we show here that bowhead whale fibroblasts undergo oncogenic transformation after disruption of fewer tumor suppressors than required for human fibroblasts. Instead, analysis of DNA repair revealed that bowhead cells repair double-strand breaks with uniquely high efficiency and accuracy compared to other mammals. Further, we identified two proteins, CIRBP and RPA2, that are present at high levels in bowhead fibroblasts and increase the efficiency and fidelity of DNA repair in human cells. These results suggest that rather than possessing additional tumor suppressor genes as barriers to oncogenesis, the bowhead whale relies on more accurate and efficient DNA repair to preserve genome integrity. This strategy that does not eliminate cells but repairs them may be critical for the long and cancer-free lifespan of the bowhead whale. Our work demonstrates the value of studying long-lived organisms in identifying novel longevity mechanisms and their potential for translation to humans.

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A CDKN2C retroduplication in Bowhead whales is associated with the evolution of extremely long lifespans and alerted cell cycle dynamics

Cited by 2 publications

References 138 publications

Cetacean Evolution: Copulatory and Birthing Consequences of Pelvic and Hindlimb Reduction

Cetacean Evolution: Copulatory and Birthing Consequences of Pelvic and Hindlimb Reduction

DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale

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