Systems-level chromosomal parameters represent the suprachromosomal basis for non-random chromosomal arrangement in human interphase nuclei

Abstract

Forty-six chromosome territories (CTs) are positioned uniquely in the human interphase nuclei, wherein each of their position can range from the center of the nucleus to its periphery. A non-empirical basis for their non-random arrangement remains unreported. Here, we derive a suprachromosomal basis of that overall arrangement (which we refer to as a CT constellation), and report a hierarchical nature of the same. Using matrix algebra, we unify intrinsic chromosomal parameters (e.g., chromosomal length, gene density, the number of genes per chromosome), to derive an extrinsic effective gene density matrix, the hierarchy of which is dominated by the extrinsic mathematical coupling of HSA19, followed by HSA17 (human chromosome 19 and 17, both preferentially interior CTs) with all CTs. We corroborate predicted constellations and the effective gene density hierarchy with published reports from fluorescent in situ hybridization based microscopy and Hi-C techniques, and delineate analogous hierarchy in disparate vertebrates. Our theory accurately predicts CTs localized to the nuclear interior, which interestingly share conserved synteny with HSA19 and/or HSA17. Finally, the effective gene density hierarchy dictates how inter-CT permutations represent plasticity within constellations and we suggest that a differential mix of coding with noncoding genome may modulate the same.