A role of telomerase to eliminate the cost of reproduction depending on the type of reproduction strategy
The telomere-related function of telomerase requires passage into S phase, and appears to be coupled to cell proliferation (Blasco 2007). Regrettably, most of the non-model organism studies mentioned above did not provide detailed information relating telomerase activity to DNA replication or tissue proliferation status, and the presence of telomerase in post-mitotic tissues, if observed, was explained by a non-canonical, and yet unknown, function of telomerase (reviewed in Gomes et al. 2010). In this regard, it is useful to mention that a wide range of TERT alternatively spliced variants were discovered in a variety of animal species, and TERT alternative splicing is thought to be linked to non-canonical telomerase functions such as those in cell proliferation, cancer development, or regeneration process (Yi et al. 2001; Hrdličková et al. 2012; Listerman et al. 2013; Lai et al. 2017; Slusher et al. 2020; Penev et al. 2022). The investigation of the evolutionary history of TERT across different metazoan taxa revealed that the selection of exons for alternative splicing appears to be highly variable between taxa, indicating diverse functions of TERT involved in animal life histories (Lai et al. 2017). Based on this and the data I am presenting below it is tempting to ask whether telomerase may act as one of reproductive fitness traits.
Reproduction is an energetically costly activity that increases metabolic rates, ROS production, and susceptibility to oxidative stress, and it is hypothesized that oxidative stress may represent a mechanistic link for the inverse relationship between reproduction and lifespan in both vertebrate and invertebrate models that acts independently of energy allocation (Alonso-Alvarez et al. 2004; Wiersma et al. 2004; Krůček et al. 2015; Sharick et al. 2015; Colominas-Ciuró et al. 2017; Costantini 2018). Resistance to oxidative stress plays a significant role in shaping fecundity; for instance, higher fecundity rates were observed in individuals with higher oxidative protection (Bize et al. 2008). It is well established that oxidative stress in humans is implicated in pathological processes in the reproductive tract that contribute to infertility and poor pregnancy outcomes, and treatments based on strategies to boost the exhausted antioxidant defense of the reproductive microenvironment have been suggested (Adeoye et al. 2018). Furthermore, in passerine birds, it has been demonstrated that resistance to oxidative stress is decreased during their reproduction and that breeding activity increases susceptibility to oxidative stress (Alonso-Alvarez et al. 2004; Wiersma et al. 2004). In agreement with the assumption that breeding individuals are more susceptible to oxidative damage, engaging organisms in reproduction accelerates telomere loss (Kotrschal et al. 2007; Heidinger et al. 2011; Bauch et al. 2013).
On the other hand, there are numerous studies showing that increased breeding constraints or reproductive status appear to prioritize self-maintenance as documented by the increased lifespan expectancy, telomere length, telomerase activity, or antioxidant defense. It has been demonstrated that (1) workers in many eusocial insect species restore their ability to reproduce if the queen in the colony has been lost, and the transition of the workers into reproductive state is associated with their substantial lifespan extension (Hartmann and Heinze 2003; Dixon et al. 2014; Kohlmeier et al. 2017; Kuszewska et al. 2017; Majoe et al. 2021) and improved resilience to oxidative stress (Schneider et al. 2011; Lucas and Keller 2018; Negroni et al. 2019; Majoe et al. 2021). (2) It has been shown that in contrast to the decline of antioxidant protection during mating in the short-lived passerine birds (Alonso-Alvarez et al. 2004; Wiersma et al. 2004; Kotrschal et al. 2007; Heidinger et al. 2011; Bauch et al. 2013), the long-lived Adélie penguins exhibited an increased antioxidant defense and unchanged telomere length in response to breeding efforts (Beaulieu et al. 2011). (3) The positive correlation between telomere length (and presumably telomerase activity), age and reproduction effort were observed in the edible dormice (Glis glis ), a hibernating long-lived rodent with a lifespan reaching 13 years. Although telomere length in this species is shortened over the hibernation season during periods of rewarming, which is associated with increased oxidative stress, it is elongated during the summer active season, when the animals mate. Longitudinal telomere length measurements revealed that the telomere-length re-elongation resulted in a gradual telomere lengthening with age of the individuals together with the likelihood of their reproduction (Hoelzl et al. 2016). (4) A lifelong somatic activity of telomerase accompanied by steady or even increasing reproduction rate with advancing age is observed in numerous reptile or fish species with indeterminate growth (Gomes et al. 2010; Schwartz and Bronikowski 2011). For instance, bigmouth buffalo (Ictiobus cyprinellus ), which displays some of the longest lifespans among vertebrates (> 100 years), has indeterminate growth and fecundity that increases with size and thus with age of individuals. In contrast to the common expectation, no telomere length decline was observed in old individuals of this species, along with declines in other physiological systems such as stress response and immune function; instead, all the tested parameters improved their efficiencies with age (Sauer et al. 2021). (5) It is well-known that the fertility rate of termite queens increases with age along with their body mass, which, based on the evidence shown above, appears to be consistent with their increasing somatic telomerase activity (Adams and Atkinson 2008; Adams et al. 2008; Nozaki and Matsuura 2019; Koubová et al. 2021a).
It is widely known that body mass in terrestrial mammals is negatively correlated with the fecundity rate of the species (Allainé et al. 1987; Werner and Griebeler 2011), which is reflected by the litter size, interlitter intervals, or gestation length. Based on this assumption, we can ask whether the necessity to maintain telomerase activity in somatic cells of small but highly fecund mammal species observed by Gomes et al. (2010) reflects a different reproduction strategy of the species and their specific demands during reproduction rather than their body size. The somatic telomerase activity or longer telomeres (> 25kb) do tend to be correlated with shorter gestation periods, as observed in Eulipotyphia, Chiroptera, and even two Carnivora species (steppe polecat and tiger); in Rodentia, Lagomorpha, Afrosoricida, and Macroscelidea they are associated with short gestation periods along with multiple litters per year, and in some cases also with the increased litter size (Figure 1). Despite the lack of telomerase activity, Diprotodontia have short gestation periods (Figure 1), which, however, might reflect that youngs in the species are born at a precocious stage of development.
Based on this observation, it is tempting to speculate that somatic telomerase activity in eusocial insect reproductives, as well as in the small mammals or potentially other animal or plant species, may serve a non-canonical function of protecting individuals against reactive oxygen species produced due to exacerbated metabolic stress during reproduction, and may simply reflect a more widespread phenomenon.
Although validity of this hypothesis needs to be tested, we can infer from all the data that telomerase expression patterns differ greatly across species, life stages, and conditions, implying that telomerase is involved in the organism’s adaptive potential and individual fitness, and that telomerase expression might co-evolved as a pleiotropic regulator involved in the life-history trade-offs between growth, maintenance, and reproduction. More precise information connecting telomerase activity to distinct reproductive strategies and lifespan expectancies, along with different cellular, physiological, and ecological features in various species across the animal and plant kingdoms, would help us better understand the role of telomerase in this aspect. We can assume that resolving the connections between these trade-offs would lead to new and intriguing directions for ecology and evolutionary biology study.
Conflicts of Interest Statement Author declares no conflict of interest.
Acknowledgements I thank James Mason and anonymous reviewers for their careful reading of my manuscript and their many insightful comments and suggestions. This study was supported by Strategy AV21, Diversity of Life and Health of Ecosystems.