Coherence, transformation, and breakdown in living systems: part I — the common higher-order regulatory architecture (CHORA) hypothesis

Abstract

The coherence of living systems extends beyond the lifespan of the individual organism: it persists across biological lineages, through the turnover of organisms and change across deep evolutionary time. This paper terms this phenomenon evolutionary coherence, the lineage-scale expression of a more general property, biological coherence, whose organism-scale expression systems biology has characterised while its evolutionary counterpart has not. Biological coherence is analysed through four aspects — stability, transformation, connectivity, and coordination — each expressed at both the lineage and the organism scale. Their lineage-level manifestations appear in familiar but unreconciled patterns: persistent morphologies, punctuated transformation, structured hybridisation, and the channelled forms evolutionary change repeatedly takes. At the organism scale the same aspects govern the maintenance of organised function and its breakdown, including the convergence of distinct systemic diseases on shared signatures of regulatory dysfunction. Such patterns are not readily accommodated by the foundational ideas of evolutionary biology and biomedicine, which engage auxiliary hypotheses to account for them; some point toward higher-order organisation but stop short of articulating it as primary. Proceeding by abductive inference, the paper specifies the requirements a unifying account must meet, then surveys the molecular evidence and develops a systems model of their operation. The architectures examined are hierarchical gene regulatory networks, bow-tie physiological regulation, germline regulatory systems, the regulation of repetitive DNA, and centromere identity. The framework is articulated as the CHORA Hypothesis: that a Common Higher-Order Regulatory Architecture, common to the organism and the lineage, operates as an integrated level across organisms and generations; that the germline is its principal conduit; that the features sustaining coherence also underlie its failure; and that its disruption at the organism level underlies these convergent signatures of dysfunction. The architecture is not a further agency but the largely conserved higher-order organisation realised by established molecular processes — transposable-element activity foremost among them — and through which coherence is sustained. These processes are its molecular signatures; the architecture’s own nature is left open. Health and entrenched disease are, on this account, alternative regimes of the one architecture. Part II develops the discriminating predictions and systemic-health implications.

The authors' abstract, as published at the source. Frontiers in Systems Biology, 2026 · DOI ↗