Telomerase as non-functional phylogenetic relict in small and
short-lived animals?
While most mammalian adults, including humans, express telomerase almost
exclusively in the germline and a few specialized cell types and have
short telomeres (< 25 kb), most rodents express telomerase in
both the germline and a wide range of somatic tissues and have long
telomeres (25-150 kb) (Gomes et al. 2011). It suggests that rodents do
not use telomere length to regulate replicative aging. A similar lack of
telomere-based replicative aging is predicted in Lagomorpha (rabbits,
pikas, and hares), as prolonged tissue cultures derived from various
lagomorph species show no growth arrest or decrease in doubling time but
have either very long telomere arrays or detectable telomere activity
(Forsyth et al. 2005). Similarly, very long telomeres and expression of
telomerase were observed in adult tissues in species of Afrosoricida
(golden moles and tenrecs), Didelphimorphia (opossums), and
Macroscelidea (elephant shrew) (Gomes et al. 2011). A comparative study
of telomerase activity and telomere length revealed that the ancestral
mammalian phenotype had human-like telomeres with repressed telomerase
activity, and the human-type of telomeres was switched to rodent-type at
least 5-7 times during mammalian evolution. Furthermore, it was
discovered that telomere length in mammals inversely correlates with
lifespan (longer telomeres are found in short-lived mammal species) and
telomerase activity in somatic cells inversely correlates with body mass
(telomerase activity in somatic cells is found in small mammal species
such as small rodents) (Seluanov et al. 2007; Gomes et al. 2010).
Body size and lifespan are factors that influence cancer risk because
cancer develops through somatic evolution with genetic and epigenetic
instability causing fitness variation among cells. Therefore, one can
assume that larger organisms, which typically have longer lifespans, are
more susceptible to cancer. In fact, however, there is no correlation
between the body size, longevity, and cancer across species (known as
Peto’s Paradox) (Caulin and Maley 2011).
To explain the Peto’s paradox, it has been suggested that larger and
longer-lived mammals repress telomerase activity in their somatic cells
as protective mechanism against cancer development, and accordingly,
small short-lived mammals have telomerase widely active, as there is no
need to repress it (Seluanov et al. 2007). On the other hand, this
assumption may evoke the idea that telomerase in these species is
present only as non-functional phylogenetic relict, and this “presence
without purpose’ can be questioned regarding why it is worthy for cells
to express telomerase (or anything else) if there is no need for it.
Furthermore, there is substantial evidence that cancer incidence is a
taxonomically widespread phenomenon, observed both in captivity and in
wild populations, with no increase in cancer incidence in the long-lived
indeterminate growers (Athena Aktipis et al. 2015; Olsson et al. 2018;
Kitsoulis et al. 2020). For example, neoplasia was found at necropsy in
2.75 % of mammals, 1.89 % of birds, and 2.19 % of reptiles.
Additionally, neoplasia has not been reported in Galapagos giant
tortoises (Effron et al. 1977), which live for more than 150 years and,
like many other reptile species, are ectotherms with indeterminate
growth (Hariharan et al. 2016; Hoekstra et al. 2020). This collectively
indicates that the risk of cancer is not elevated in the species with
indeterminate growth and somatic telomerase activity, and that the
proposed telomerase repression as a cancer protection is less
straightforward than was previously believed (Olsson et al. 2018).
Finally, a plenty of evidence suggests that numerous anti-cancer
mechanisms other than telomere attrition have evolved (Caulin and Maley
2011; Tian et al. 2018).