Convergent adaptation of cellular machineries in the evolution of large body masses and long life spans

Abstract

In evolutionary terms, life on the planet has taken the form of independently living cells for the majority of time. In comparison, the mammalian radiation is a relatively recent event. The common mammalian ancestor was probably small and short-lived. The "recent" acquisition of an extended longevity and large body mass of some species of mammals present on the earth today suggests the possibility that similar cellular mechanisms have been influenced by the forces of natural selection to create a convergent evolution of longevity. Many cellular mechanisms are potentially relevant for extending longevity; in this assay, we review the literature focusing primarily on two cellular features: (1) the capacity for extensive cellular proliferation of differentiated cells, while maintaining genome stability; and (2) the capacity to detect DNA damage. We have observed that longevity and body mass are both positively linked to these cellular mechanisms and then used statistical tools to evaluate their relative importance. Our analysis suggest that the capacity for extensive cellular proliferation while maintaining sufficient genome stability, correlates to species body mass while the capacity to correctly identify the presence of DNA damage seems more an attribute of long-lived species. Finally, our data are in support of the idea that a slower development, allowing for better DNA damage detection and handling, should associate with longer life span.

Keywords: Aging; Body size; Convergent evolution; DNA damage; Genomic stability; Longevity; Replicative senescence.

Fig. 1

Convergent evolution. a Convergent evolution of flying: bird, bats, pterosaurs and insects have clear anatomical differences in their wing structure but they all evolved flying. b Different cellular machineries may have been optimized during the independent evolution of large body masses. c Different cellular machineries may have been optimized during the independent evolution of long life spans. In parenthesis are reported some key supporting references. See text for in depth description

Fig. 2

Large body sizes and significant longevities evolved multiple times. The numbers inside the arrows indicate the fold difference in maximum longevity and adult weight (from the smaller to the higher value). The Phylogenetic tree was built following phylogenetic information in Gomes et al. ; Richards et al. ; Jameson Kiesling et al. . Maximum longevity and adult weight were taken from the AnAge database (Tacutu et al. 2013). Time scale is given only as a reference and it is not meant to be accurate (My, millions of years ago)

Fig. 3

Two expectations from the hypothesis that the maximum number of cellular divisions in vitro relates to species longevity. a Proliferation competent cells from old donors are expected to accomplish less cell division than cells from young donor. b Proliferation competent cells from short-lived species are expected to accomplish less cell divisions than cells from long-lived species (e.g., house mouse max. longevity is 4 years; little brown bat max. longevity is 34 years; max longevity from the AnAge database Tacutu et al. 2013)

Fig. 4

DNA-end biding assay. a A pUC18 plasmid is digested with both PuuII and EcoRI restriction endonuclease enzymes to generate a 144-base pair probe, then the linear probe is labeled with ³²P. b Competitive binding between protein nuclear extract, excess unlabeled circular plasmids and labeled linear probes. c Different mixtures, containing constant amounts of unlabeled plasmid and labeled probe, but increasing amounts of nuclear extracts, are separated on a 5% polyacrylamide gel at 20–25 mA. The slowing down in the probe migration (shift) is evidence of the formation of complexes between DNA-ends and proteins. DNA-end binding activity is the amount of protein required to bind 50% of the probe. This amount is obtained by interpolation in a plot displaying “fraction of probe bound” versus “protein amounts” (Getts and Stamato 1994)