Club EvMed: Of Mice and Elephants: Trade-Offs of Tumor Suppressor Duplication and Body Size Evolution in Afrotheria

Tuesday, June 29th at 12pm EDT/18:00 CEST

Join us for a conversation with Juan Manuel Vazquez, Postdoctoral Scholar at the University of California-Berkeley. Peto’s Paradox describes the observation that while cancer risk is correlated with body size and lifespan within species, no such correlation holds between species. This indicates that large, long-lived species have evolved enhanced cancer protection mechanisms, and that these mechanisms may be used to treat and even prevent human cancers, and extend the human healthspan. The recent expansion of body size in elephants relative to other members of their resident clade of Afrotheria led us to explore how both body size and lifespan evolved in this group. Unexpectedly, we found that tumor suppressor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk. In our talk, we will begin with a summary of these findings, then move on to a discussion of the implications of tumor suppressor duplicates in the development and fitness of various animals, and of a new paradox: how can an organism’s body size expand given enhanced genetic shackles on growth?

Attendees are encouraged to read Vazquez and Lynch 2021, “Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk” and García-Cao et al. 2002, “‘Super p53’ mice exhibit enhanced DNA damage response, are tumor resistant and age normally.” Sign up here for the meeting link: https://duke.zoom.us/meeting/register/tJUpfu2rrjgvHNUJVdX4ddvbEaa9Vv1di0wR.