Hypothesis

Telomeres in reef‑building corals act as a quantum‑informational clock whose entropy, reflected in TERRA secondary‑structure diversity, rises under metabolic stress and predicts symbiont loss before visible bleaching.

Rationale

• Classical replicative models cannot explain telomere dynamics in largely post‑mitotic coral tissues Stylophora pistillata dark‑induced bleaching correlates with telomere shortening.
• Active telomerase maintains length‑regulation capacity, yet telomeres still shorten under stress, implying a non‑replicative signaling role Scleractinian corals possess active telomerase.
• Ocean acidification reshapes the microbiome toward sediment‑like communities and impairs Symbiodiniaceae nutrient provisioning, creating metabolic imbalance that could increase genomic informational entropy Ocean acidification alters coral microbiomes, Impairs Symbiodiniaceae nutritional provisioning.
• The Information Theory of Aging treats telomere shortening as an entropy increase rather than a division counter The Information Theory of Aging.
• TERRA transcripts form G‑quadruplexes and other structures; their structural heterogeneity can be quantified as an informational entropy metric, a proxy not yet explored in symbiotic cnidarians.

Novel Mechanistic Insight

We propose that stress‑induced shifts in cellular NAD+/NADH ratios alter the activity of RNA helicases (e.g., DDX5) that remodel TERRA structures. Increased helicase activity expands the conformational ensemble of TERRA, raising its Shannon entropy. This elevated TERRA entropy destabilizes shelterin complex binding, exposing telomeric DNA to oxidative damage and triggering a DDR‑like cascade that suppresses symbiosome maintenance, driving bleaching independent of cell division.

Testable Predictions

1. Correlation: In Acropora millepora exposed to graded pCO₂ (400, 800, 1200 µatm) and temperature (26, 30, 34 °C), TERRA structural entropy (measured by SHAPE‑Seq or NMR‑derived ensemble diversity) will increase linearly with both telomere shortening (qPCR) and symbiont density loss (chlorophyll a fluorescence), preceding visible bleaching.
2. Perturbation: Pharmacological inhibition of DDX5 with a specific RNA helicase inhibitor (e.g., RK‑33) will attenuate TERRA entropy rise under high‑pCO₂/heat, preserve telomere length, and maintain symbiont populations despite stress.
3. Rescue: Overexpressing a telomerase‑independent TERRA‑binding mutant that locks TERRA into a low‑entropy G‑quadruplex will suppress DDR markers (γH2Av) and bleaching even when telomeres are artificially shortened via CRISPR‑Cas9 telomere truncation.
4. Falsifiability: If TERRA entropy does not change with stress, or if manipulating DDX5/TERRA fails to affect telomere integrity or symbiont stability under identical conditions, the hypothesis is refuted.

Experimental Outline (brief)

• Collect nubbins, acclimate, expose to factorial stress matrix.
• Extract RNA for SHAPE‑Seq to compute TERRA ensemble entropy; parallel qPCR for telomere length (T/S ratio); symbiont quantification via clade‑specific ITS2 metabarcoding.
• Apply DDX5 inhibitor or vehicle controls; include transgenic lines expressing TERRA‑binding mutant (generated via CRISPR‑HDR).
• Assess bleaching (photochemical efficiency Fv/Fm), DDR markers (immunostaining for γH2Av), and telomerase activity (TRAP assay).

Implication: Demonstrating that telomeric informational entropy, not merely length, couples environmental metabolic stress to symbiosis breakdown would reframe coral climate resilience as a problem of information preservation, opening avenues for epigenetic‑based interventions.