**6. Conclusion**

systems of so called hypercycles. With environmental separation by the emergence of units as cells and specialization of subunits, then genomes have developed as specialized keepers of the blueprint needed to maintain, regulate, and develop this syntropic machinery. Since genetic information is physically stored in molecular structures with dedicated architecture and dynamics, it is thus also obvious that the material carrier for the storage, usage, and replication of genetic information co-evolved inseparably. Yet another inevitable consequence of our results leading to the consistent statistical systems genome mechanic framework is indeed our proof [26, 27] that architecture, dynamics, and DNA sequence are co-evolutionary unseparably entangled (in a quantum mechanical sense): All architecture/dynamics levels have not only left a footprint on the DNA sequence level but beyond also all levels have left a footprint on all other levels with an astonishing degree of detail (see Section 2.4). Consequently, the co-evolution of all levels has also co-evolved not only to a higher degree than previously thought, but also indeed as an entire system where all levels are (equally ?)

**Phenotype**

**Environment** macro embedding system properties

**Nucleus Chromosome Chromosome Arm Chromatin Rosee Chromatin Loop Chromatin Quasi-Fibre Nucleosome DNA Double Helix**

**Lamarckian Evolution** self-refrenced manipulation engineering the fi est

**Genotype**

**Invironment** micro constituting system properties

**Figure 5.** Genome ecology emerging from the system mechanics of genomes in relation to the genotype-phenotype entanglement and its embedding in- and environment: Genomes are interwoven holistic multi-scale hierarchic systems entities in which all organizational levels are also manifest, i.e. fingerprinting, on all other levels. Thus, immediately each level is a phenotype of its underlying genotype immediately conditioning back on it recursively. Thus, both genotype and phenotype are entangled inseparably in a (due to the involvement and entanglement of all levels) multilistic manner. In consequence this not only unites Darwinian and Lamarckian evolutionary paradigms, but also embeds and relates

genomes with their in- and environment, and thus giving rise to a general genome ecology.

determinant (**Figure 5**).

84 Chromatin and Epigenetics

**Darwinian Evolution** random mutations survival of the fi est

> Nature has created ever more complex forms of life by creating structural and dynamical islands of systems with specialized organelles such as genomes being responsible for storage, access, and replication of the information for their persistence and development. Despite the epic quest to determine the details and origin of inheritance, only recently we were finally able to fill the debated gaps of the central part of genome architecture and dynamics - despite the pioneering

works of the last 170 years - by establishing that nucleosomes compact into a quasi-fibre which is folded into stable loops, forming stable multi-loop aggregates/rosettes connected by linkers creating chromosome arms and entire chromosomes [26, 27]. Although the heuristics of the field leads already to a sound basis, this could only be achieved - as we summarized here - by a highly integrated systems approach linking holistically i) a by far superior selective chromosome interaction (T2C) technique, ii) a novel *in vivo* FCS dynamic method, iii) a novel analytical approach and improved super-computer simulations, and iv) finally scaling analysis of the 3D-architecture and the DNA sequence itself. Including the heuristics of the field this leads to a consistent picture of genome organization, which match all the criteria necessary for storage, transcription, and replication as one would expect them as the outcome of Darwinian natural selection and Lamarkian self-referenced manipulation as shown here. In parallel, a multilistic systems statistical mechanics with uncertainty principles has emerged while reaching the fundamental resolution limits in the above holistic approach, which represents a theoretical framework which also reunites the overall far from thermodynamic equilibrium notion with local hierarchic substance stability. Beyond, the tight entanglement of genome levels having left footprints on all levels, has not only shown that genomes have evolved as an entire system, but also the multilistic entanglement between genotype and phenotype. Hence, the natural outcome of Darwinian natural selection and Lamarkian self-referenced manipulation is united in a genome ecology framework, which we consider a major step in the systems theory of life. Thus, this not only leads to a solid basis for sequencing genetic information holistically and thus for applied diagnostics and treatment of disease, as well as future genome manipulation and engineering efforts, but more importantly paves the path to a true understanding of genomes, their function and evolution, and thus of life in general - earthbound, extra-terrestrial, or artificial.

also go to all those institutions, universities, and companies providing us computational grid resources: the German D-Grid, the European Grid Initiative EGEE, as well as the Erasmus Computing Grid the Almere Grid, and all the unnamed computing grids there is access through via these. Very special thanks go also to all the world-wide distributed and unnamed

A Consistent Systems Mechanics Model of the 3D Architecture and Dynamics of Genomes

http://dx.doi.org/10.5772/intechopen.89836

87

**Movie 1.** Brownian Dynamics simulated decondensation from a metaphase starting configuration of a simulated Multi-Loop-Subcompartment model with 126 kbp loops and linkers with segment length of 50 nm (~5.2 kb) [26]. The whole 750 ms long movie shows how abruptly the metaphase chromosome expands due to its high density while opening the linker, which is constrained/condensed/pulled into a loop in metaphase. Nevertheless, the rosettes form distinct chromatin territories in which the loops do not intermingle freely in contrast to other models (see Introduction) such as the RW/GL model (**Figure 2**). The final shape and form in a whole nucleus would be determined by the limitations the other adjacent chromosomes provide (for more details see [22]). The different densities during decondensation also resemble nicely the conditions of shorter linkers, general genome regions with higher densities, or also the variation of nuclear volumes. Notably, the intrinsic movement of the chromatin fibre is clearly taking place on the millisecond scale, and hence, obviously a topological preformed

**Movie 2.** Brownian Dynamics simulation of the consensus architecture (i.e. with the real measured loop and linker sizes) of the of the IGF/H19 region at HS11p15.5–15.4 (**Figure 3**), with a segment length of 20 nm (~2.0 kbp; colours of loops like in **Figure 3** middle, with additional linkers at the beginning and end of the region in red; for details see [26]). The whole movie encompasses 146 ms and shows the high intrinsic dynamics of the loops and the loop aggregate/rosette. Obviously, the single subchromosomal domains are constrained by the subsequent subchromosomal domains. Hence, and also obviously a topological preformed architecture would dissolve within seconds if it would not be stable [26, 27]. Nevertheless, the loop aggregates/rosettes form distinct subchromosomal domains in which the loops do not intermingle freely in contrast to other models (see Introduction) such as the RW/GL model (**Figure 2**). The final shape and form in a whole nucleus would be determined by the limita-

Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Rotterdam,

architecture would dissolve within seconds if it would not be stable [26, 27].

tions adjacent chromosomes provide (for more details see [22]).

Address all correspondence to: ta.knoch@taknoch.org

**Author details**

Tobias A. Knoch

The Netherlands

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**Legends Movie 1 and 2**

Video files available at: https://bit.ly/34KCuxe
