Changes in gene expression are thought to regulate the differentiation process intrinsically through complex epigenetic mechanisms. In fundamental terms, however, this assumed regulation refers only to the intricate propagation of changes in gene expression or else leads to logical inconsistencies. The evolution and self-regulatory dynamics of individuated multicellularity also lack a unified and falsifiable description. To fill this gap, I computationally analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell-type/developmental-periods samples. My analysis of genomic regions adjacent to transcription start sites generated a profile from pairwise partial correlations between histone modifications controlling for the respective mRNA levels for each cell-type/developmental-period dataset. I found that these profiles, while explicitly uncorrelated to transcript abundance by construction, associate strongly with cell differentiation states. This association is not expected if cell differentiation is, in effect, regulated by epigenetic mechanisms. Based on these results, I propose a falsifiable theory of individuated multicellularity, which relies on the synergistic coupling across the extracellular space of two stochastically independent "self-organizing" systems constraining histone modification states at the same sites. This theory describes how the multicellular individual—understood as an intrinsic, higher-order constraint—emerges from proliferating undifferentiated cells, and may explain the intrinsic regulation of gene transcriptional changes for cell differentiation and the evolution of individuated multicellular organisms.
- Downloaded 2,901 times
- Download rankings, all-time:
- Site-wide: 2,041 out of 92,411
- In developmental biology: 25 out of 2,737
- Year to date:
- Site-wide: 16,754 out of 92,411
- Since beginning of last month:
- Site-wide: 16,549 out of 92,411
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!