Data from: TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

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.