@article{TEXTUAL,
      recid = {9854},
      author = {Sulak, Michael and Fong, Lindsey and Mika, Katelyn and  Chigurupati, Sravanthi and Yon, Lisa and Mongan, Nigel P.  and Emes, Richard D. and Lynch, Vincent J.},
      title = {<i>TP53</i> copy number expansion is  associated with the evolution of increased body size and an  enhanced DNA damage response in elephants},
      journal = {eLife},
      address = {2016-09-19},
      number = {TEXTUAL},
      abstract = {A major constraint on the evolution of large body sizes in  animals is an increased risk of developing cancer. There is  no correlation, however, between body size and cancer risk.  This lack of correlation is often referred to as ’Peto’s  Paradox’. Here, we show that the elephant genome encodes 20  copies of the tumor suppressor gene TP53 and that the  increase in TP53 copy number occurred coincident with the  evolution of large body sizes, the evolution of extreme  sensitivity to genotoxic stress, and a hyperactive TP53  signaling pathway in the elephant (Proboscidean) lineage.  Furthermore, we show that several of the TP53 retrogenes  (TP53RTGs) are transcribed and likely translated. While  TP53RTGs do not appear to directly function as  transcription factors, they do contribute to the enhanced  sensitivity of elephant cells to DNA damage and the  induction of apoptosis by regulating activity of the TP53  signaling pathway. These results suggest that an increase  in the copy number of TP53 may have played a direct role in  the evolution of very large body sizes and the resolution  of Peto’s paradox in Proboscideans.},
      url = {http://knowledge.uchicago.edu/record/9854},
}