Unified theory of human genome reveals a constrained spatial chromosomal arrangement in interphase nuclei

We investigate a densely packed, non-random arrangement of forty-six chromosomes (46,XY) in human nuclei. Here, we model systems-level chromosomal crosstalk by unifying intrinsic parameters (chromosomal length and number of genes) across all pairs of chromosomes in the genome to derive an extrinsic parameter called effective gene density. The hierarchical clustering and underlying degeneracy in the effective gene density space reveal systems-level constraints for spatial arrangement of clusters of chromosomes that were previously unknown. Our findings corroborate experimental data on spatial chromosomal arrangement in human nuclei, from fibroblast and lymphocyte cell lines, thereby establishing that human genome constrains chromosomal arrangement. We propose that this unified theory, which requires no additional experimental input, may be extended to other eukaryotic species with annotated genomes to infer their constrained self-organized spatial arrangement of chromosomes.