Counting Cell Divisions: A Computational Approach Using DNA Tandem Repeats

What is it about?

Repetitive DNA occurs in all domains of life—Bacteria, Archaea and Eukaryota— and can be grouped into two categories: interspersed repeats, such as transposable elements occurring in multiple loci across the genome, and tandem repeats (TRs) that occur in a single locus. This manuscript presents a compelling exploration of the role of DNA tandem repeats (TRs) in counting cell divisions, employing a computational model that could significantly advance the understanding of cell biology and epigenetics. The integration of TRs as iterable objects not only offers a fresh perspective but also provides a potential framework for investigating fundamental biological processes. The research could pave the way for novel insights into cellular mechanisms and their implications for development and disease. Overall, this manuscript aims to be a contribution to the scientific community, encouraging deeper discussions about the noncanonical roles of TRs in genomic regulation.

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Why is it important?

The lineage of the roundworm Caenorhabditis elegans is absolutely invariable, autonomous, and genetically established without exceptions (Cole et al., 2023): its midgut progenitor (E blastomere), isolated and cultured in vitro in the absence of morphogens, undergoes five (incomplete) division rounds as in the whole embryo (Robertson et al., 2014); an embryonic intestine of 20 cells is generated, not 32 (25 ) because only 4 cells (unerringly the same) carry out the fifth division, while the remaining 12 stop dividing after four rounds (Regolini, 2024). Similarly, in the embryo of the fruit fly Drosophila melanogaster, the early 13 divisions are precisely counted (Ahmad and Henikoff, 2022) without active morphogens, that will work later (Shvartsman et al., 2008) or other molecular clocks (early divisions occur in a syncytium without cell-cell communication involving transmembrane signaling; maternal morphogenetic mRNAs have different concentration gradients along the developmental syncytium). (Abouchar et al. 2014) measured the precision of left–right and interindividual fly wing vein patterns: “Wing vein patterns are specified with identical spatial precision and are reproducible to within a single-cell width. The early fly embryo operates at a similar degree of reproducibility, suggesting that the overall spatial precision of morphogenesis in Drosophila performs at the single-cell level. Could development be operating at the physical limit of what a biological system can achieve?”

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