Institute Lorentz for Theoretical Physics, Leiden University, Niels Bohrweg 2, 2333 CA Leiden, the Netherlands.
Phys Rev E. 2019 Jan;99(1-1):012422. doi: 10.1103/PhysRevE.99.012422.
The elasticity of the DNA double helix varies with the underlying base pair sequence. This allows one to put mechanical cues into sequences that in turn influence the packaging of DNA into nucleosomes, DNA-wrapped protein cylinders. Nucleosomes dictate a broad range of biological processes, ranging from gene regulation, recombination, and replication to chromosome condensation. Here we map base pair sequences onto graphs and use shortest paths algorithms to determine which DNA stretches are easiest or hardest to bend inside a nucleosome. We further demonstrate how genetic and mechanical information can be multiplexed by studying paths through graphs of synonymous codons. Using this method we find that nucleosomes can be placed by mechanical cues nearly everywhere on the genome of baker's yeast (Saccharomyces cerevisiae).
DNA 双螺旋的弹性随其基础碱基对序列而变化。这使得人们可以将机械线索放入序列中,进而影响 DNA 包装成核小体,即 DNA 包裹的蛋白质圆柱体。核小体决定了广泛的生物学过程,包括基因调控、重组和复制,以及染色体凝聚。在这里,我们将碱基对序列映射到图上,并使用最短路径算法来确定 DNA 链在核小体内部最容易或最难弯曲的位置。我们进一步通过研究同义密码子图的路径来展示如何将遗传和机械信息进行复用。使用这种方法,我们发现机械线索几乎可以将核小体放置在面包酵母(酿酒酵母)基因组的任何位置。