Editorial: Evolution of short genomic regions: discoveries, methods, and challenges Piontkivska et al. 10.3389/fbinf.2026.1821711

Abstract

Genome complexity is an umbrella term that reflects the existence of multiple structural levels of genome organization, from compositional biases and differential gene expression to higher-order genome architectures. This includes whole genome duplications, pan-genomes, and 3D-folding, as well as how these features are regulated to become actionable instructions for a cell. A central challenge in studying genome complexity is therefore methodological: how can complexity be robustly defined, detected, and quantified in practice, particularly across divergent taxonomic groups. Existing approaches vary widely, with some emphasizing large-scale genome architecture and others focusing on gene structure, sequence composition, or functional output. The second, closely related challenge, concerns functional interpretation: how do we predict and validate functional implications of various aspects of genomic complexity. The third challenge is driven by the selected target, whether it be coding or non-coding sequences within a genome or a comparative approach across taxonomic levels. Given the wide and inconsistent use of the term “complexity”, it remains unclear how different operational definitions relate to biological function. As a result, methodological choices such as thresholds, descriptors, and even terminology, strongly influence which features are identified as complex and how their biological relevance is inferred. This collection showcases on one hand the diversity of conceptual and methodological frameworks currently used to identify, name, and interpret low-complexity regions (LCRs) and related genomic features, but also illustrates the need for a consensus framework as authors rely on distinct, context-specific definitions of complexity, each revealing different biological insights. The common thread among this collection is the identification, across domains of life and widely different methodological approaches, of a functional role for low complexity regions, highlighting the need to develop new approaches to better understand this poorly studied feature of genomes.