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.Comment: Whole genome analysis, includes coding genome and non-coding genome,
  (18 pages, 1 Table, 3 Figures) - with edit

Fatakia, Sarosh N.

Mehta, Ishita S.

Rao, Basuthkar J.

English

arXiv

Forty-six chromosome territories (CTs) are positioned uniquely in human interphase nuclei, wherein each of their positions can range from the centre 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 largely by 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 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 localised to the nuclear interior, which interestingly share conserved synteny with HSA19 and/or HSA17. Finally, the effective gene density hierarchy dictates how permutations among CT position represents the plasticity within its constellations, based on which we suggest that a differential mix of coding with noncoding genome modulates the same

Indian Academy of Sciences

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

http://repository.ias.ac.in/106556/1/srep36819.pdf

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

Abstract

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Indian Academy of Sciences

Indian Academy of Sciences