Scaling laws of genome composition and the transition to complex multicellularity

Abstract Genome architecture reorganizes over evolutionary time to support complex multicellularity without a proportional expansion of coding DNA. We conducted a cross-kingdom comparative analysis using high-quality RefSeq assemblies annotated by the NCBI Genome Annotation Pipeline, restricting the dataset to chromosome-level or complete genomes. Scaling relationships among genome size, gene content, and coding DNA content reveal compositional transitions that distinguish prokaryotic, unicellular eukaryotic, and multicellular lineages. Beyond ∼40 Mb of genic content, coding expansion slows and saturates, indicating compositional constraints that shaped the rise of multicellularity. These results establish scaling laws that quantify how noncoding sequence expansion dominates genome growth in complex eukaryotes.