Stress-induced transposon reactivation: a mediator or an estimator of allostatic load?

Abstract

Transposons are playing an important role in the evolution of eukaryotic genomes. These endogenous virus-like elements often amplify within their host genomes in a species specific manner. Today we have limited understanding when and how these amplification events happens. What we do know is that cells have evolved multiple line of defenses to keep these potentially invasive elements under control, often involving epigenetic mechanisms such as DNA-methylation and histone modifications. Emerging evidence shows a strong link between transposon activity and human aging and diseases, as well as a role for transposons in normal brain development. Controlling transposon activity may therefore uphold the fine balance between health and disease. In this article we investigate this balance, and sets it in relation to allostatic load, which conceptualize the link between stress and the "wear and tear" of the organism that leads to aging and disease. We hypothesize that stress-induced retrotransposon reactivation in humans may be used to estimate allostatic load, and may be a possible mechanism in which transposons amplify within species genomes.

Keywords: allostasis; allostatic load; epigenetic silencing; retrotransposons; stress; transposons.

Figure 1:

An integrated model of stress-induced retrotransposon (re)activation and the allostatic load concept. Exogenous and endogenous challenges increase the allostatic load on the body, which represents an average allostatic load experienced by all cells in the organism. A consequence of this is that not all cells will experience higher allostatic load following stress; some might even experience less allostatic load. High cellular allostatic load leads to loss of epigenetic silencing in heterochromatic genomic regions, which is followed by (re)activation of retrotransposons. Losing control of retrotransposons has different consequences and tradeoffs depending on cell type. In somatic cells, it may help an individual animal to generate cellular diversity important for normal development, but may also cause genome instability which may increase the risk of disease. In germ cells, retrotransposon (re)activation may cause infertility, but also contribute to species evolvability by increasing genetic diversity. Hypothetically, a challenging environment could, by increasing the allostatic load, induce the genome-wide transposon amplification events observed in most eukaryotes, thereby representing a tool for a population/species to adapt to the challenging environment.