What modulates telomere dynamics? : Inheritance, developmental effects, and physiological challenges

Sammanfattning: Telomeres are the conservative sequence repeats located at the end of linear chromosomes that have been the focus of intensive research across many disciplines over the last four decades. They function as a cap to protect the chromosome ends from fusion to other chromosomes and to prevent chromosome degradation. Telomere shortening is thought to be involved in ageing, reflecting or even causing age-related dysregulation of bodily functions. Telomere length and telomere shortening have also gained considerable interest in the field of ecology and evolution as indicators of individual quality and mediators of life-history trade-offs. Telomere length (TL) predicts life span in many animal species but there is considerable variation in TL and shortening rate between individuals, populations and species. How does this variation come about and how is it maintained? Paper I in this thesis discusses the most prominent hypotheses in ecology and evolution that have been put forward to explain variation in TL and telomere dynamics (i.e., shortening and elongation of telomeres). It presents a framework that groups the different hypotheses based on research question or their underlying assumptions about the causal effects of telomeres on organism performance. Some of the key issues that are highlighted in this synthesis paper are that 1) the question of whether telomeres have a causal effect on ageing and life span is still debated, 2) the costs of telomere shortening and elongation remain elusive, and 3) the genetic and non-genetic contribution to variation in TL (and therefore the potential for selection to act on TL) is still not fully understood. The papers III-V in this thesis try to tackle some of these questions. Paper III aims to test whether mild inflammation (induced through repeated immune challenges), can have measurable negative effects on TL, both over the short- and the long-term and whether this results in concomitant deterioration in physiological health. To measure physiological health, we use the measurement method based on the VetScan blood analyser, which is introduced and carefully evaluated for broader use in paper II. Immune system activation had no measurable effects on TL, but the change in ambient and social environment as a consequence of the experiment design (from harsh, rather cold and large-group to benign, thermoneutral and same-sexed pairs conditions), appeared to induce substantial telomere elongation (up to 150 % increase) in the individuals with the shortest TLs. This supports the hypotheses that telomere restoration is costly and therefore primarily occurs under benign conditions. Moreover, telomere elongation occurred more frequently among individuals with the shortest TL, possibly because such individuals are closer to the lower critical threshold in TL. Paper IV and V investigate the genetic and non-genetic contribution to the variation in TL. By creating parental groups that were based on the individuals with the shortest and longest TL at birth in the population (thus manipulating the expected genetic contribution from parents to offspring) it was possible to test how genetic and non-genetic parental effects contribute to TL during the prenatal and early post-natal life stages. The results show that offspring TL at birth, but not embryo TL, was predicted by parental early-life TL group. These results are not consistent with hypotheses assuming that telomere trajectories can be predicted based on TL at the very early stages of embryonic development. However, they support the idea that telomere shortening rate rather than TL itself is inherited. To study this further, paper V examines inheritance patterns of telomere length in detail using both animal model and parent-offspring regressions. The study shows that heritability estimates of TL are moderate magnitude, and, particularly, that these estimates vary considerably depending on at which life stage/age TL measurements were compared between parents and offspring. Altogether, this thesis presents a number of novel findings that both confirm and challenge some of the current ‘telomere hypotheses’ discussed in paper I.