Coevolution of telomerase activity and body mass in mammals: from mice to beavers

Abstract

Telomerase is repressed in the majority of human somatic tissues. As a result human somatic cells undergo replicative senescence, which plays an important role in suppressing tumorigenesis, and at the same time contributes to the process of aging. Repression of somatic telomerase activity is not a universal phenomenon among mammals. Mice, for example, express telomerase in somatic tissues, and mouse cells are immortal when cultured at physiological oxygen concentration. What is the status of telomerase in other animals, beyond human and laboratory mouse, and why do some species evolve repression of telomerase activity while others do not? Here we discuss the data on telomere biology in various mammalian species, and a recent study of telomerase activity in a large collection of wild rodent species, which showed that telomerase activity coevolves with body mass, but not lifespan. Large rodents repress telomerase activity, while small rodents maintain high levels of telomerase activity in somatic cells. We discuss a model that large body mass presents an increased cancer risk, which drives the evolution of telomerase suppression and replicative senescence.

Fig. 1

Rodent phylogeny. The tree topology is based on molecular phylogenies inferred from Martin et al. (2000), Michaux et al. (2001), Murphy et al. (2001), Montgelard et al. (2002), Adkins et al. (2003), Steppan et al. (2004). Stars indicate the species with lifespan longer than 20 years.

Fig. 2

Correlation between telomerase activity, lifespan, and body mass. R² and P-values are shown for phylogenetically independent contrasts.

Fig. 3

Model explaining coevolution of telomerase activity and body mass. Evolutionary increases in body mass lead to increased cancer risk. To counteract this risk large species evolve additional tumor-suppressor mechanisms such as the repression of telomerase activity in somatic cells.