Physical Forces May Cause the HoxD Gene Cluster Elongation

Abstract

Hox gene collinearity was discovered be Edward B. Lewis in 1978. It consists of the Hox1, Hox2, Hox3 ordering of the Hox genes in the chromosome from the telomeric to the centromeric side of the chromosome. Surprisingly, the spatial activation of the Hox genes in the ontogenetic units of the embryo follows the same ordering along the anterior-posterior embryonic axis. The chromosome microscale differs from the embryo macroscale by 3 to 4 orders of magnitude. The traditional biomolecular mechanisms are not adequate to comprise phenomena at so divergent spatial domains. A Biophysical Model of physical forces was proposed which can bridge the intermediate space and explain the results of genetic engineering experiments. Recent progress in constructing instruments and achieving high resolution imaging (e.g., 3D DNA FISH, STORM etc.) enable the assessment of the geometric structure of the chromatin during the different phases of Hox gene activation. It is found that the mouse HoxD gene cluster is elongated up to 5–6 times during Hox gene transcription. These unexpected findings agree with the BM predictions. It is now possible to measure several physical quantities inside the nucleus during Hox gene activation. New experiments are proposed to test further this model.

Evolutionary lability inHoxcluster structure and gene expression inAnolislizards

“…If spatial and temporal collinearity of Hox gene expression is indeed maintained by close physical proximity of Hox genes in a compact cluster (Ferraiuolo et al 2010;Mallo and Alonso 2013;Papageorgiou 2017), invasion of TEs could interfere with Hox cluster function by increasing intergenic distances between Hox genes. Insertion of TEs could also introduce novel cis-regulatory elements (Slotkin and Martienssen 2007;Feschotte 2008;Cowley and Oakey 2013;Sundaram et al 2014), or affect chromatin modifications (Kidwell and Lisch 1997).…”

Hox Gene Collinearity May Be Related to Noether’s Theory on Symmetry and Its Linked Conserved Quantities

“…This finding supports the hypothesis of pulling forces of BM with the associated ratchet -type ordering of the Hox genes. HGC is the outcome of these forces [17,25]. The vertebrate Hox gene clusters obey a primitive symmetry of self similarity and the ratchet-type ordering of the Hox genes could be the partly conserved quantity in the Noether theory spirit.…”

“…2). In this model the forces depend on both macro and micro influences and the Hox cluster behaves like an expanding elastic spring [25,26]. In the Evolutionary process, each Hox gene of the cluster is endowed with specific features and a functional role.…”

Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity

“…As early as 2001, a biophysical model (BM) was proposed, which combines long-range gradients based mainly on diffusion, causing pulling forces at the level of theHox clusters [15][16][17][18]. For many years this model was poorly endorsed because supporting experimental evidence was lacking.…”

“…These regions (transcription factories) are studied in depth by Cook and collaborators [28]. In this model, the force F of Equation (3) depends on both macro (P) and micro (N) influences, and the Hox cluster behaves like an expanding elastic spring [17,18]. The factor P in Equation (3) varies according to the cell position along the morphogen gradient in the anterior-posterior axis.…”