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Rute da Fonseca (CIIMAR - Center for Marine & Environmental Research, Porto, Portugal)Apoptosis is a form of programmed cell death with a variety of important biological functions in mammals involving development, homeostasis, immunity and defense, spermatogenesis, and prevention of cancer. I have searched for evidence of positive selection acting on apoptosis related genes in mammals. Selection appears primarily to be driven by the immune/defense related function of these genes, but may also be related to other pleiotropic effects of the genes. Protein structure analyses reveal that multiple biochemical mechanisms are targeted by positive selection, from protein interfaces that contact directly with pathogens to different elements of signalling complexes involved in immune system development and/or response. Many of the apoptosis related positively selected genes are involved in various diseases, including cancer. Cancer related genes show a clear excess of positive selection that can be attributed to their role in apoptosis and/or immune defense, providing an example of how selective pressures on particular functions of pleiotropic genes might result in trade-offs in fitness.