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In-Nucleus Hi-C in Drosophila Cells
Published on: September 15, 2021
Evolution of chromosome organization driven by selection for reduced gene expression noise
Nizar N Batada1, Laurence D Hurst
1Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. nizar.batada@gmail.com
Nature Genetics
|July 31, 2007
Summary
Essential genes cluster in open chromatin to minimize harmful fluctuations. This genomic organization, driven by gene noise, impacts gene therapy and understanding transgenic organisms.
Area of Science:
- Genomics
- Molecular Biology
- Systems Biology
Background:
- Gene distribution on eukaryotic chromosomes is nonrandom.
- The clustering of essential genes is a known phenomenon.
- The underlying reasons for gene clustering remain poorly understood.
Purpose of the Study:
- To model and test a new hypothesis for essential gene clustering.
- To investigate the role of gene expression noise in genomic organization.
- To explore the implications of gene positioning for gene therapy and transgenic phenotypes.
Main Methods:
- Developed a computational model to simulate gene distribution and noise.
- Analyzed correlations between gene essentiality, chromatin accessibility, and gene expression noise.
- Predicted and validated key characteristics of essential gene clusters.
Main Results:
- Essential gene clusters are associated with low nucleosome occupancy and reduced gene expression noise.
- Noise-sensitive nonessential genes and genes with similar knockout fitness cluster with essential genes.
- Essential genes are rare subtelomerically, and essential gene clusters are preferentially conserved across species.
Conclusions:
- Persistent open chromatin domains act as sinks for essential genes, minimizing deleterious fluctuations in protein abundance.
- Differential noise characteristics across genomic domains drive nonrandom gene positioning.
- Understanding gene organization has significant implications for gene therapy and transgenic organism development.
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