We present a deformation energy model for predicting nucleosome positioning, in which a position-dependent structural parameter set derived from crystal structures of nucleosomes was used to calculate the DNA deformation energy. The model is successful in predicting nucleosome occupancy genome-wide in budding yeast, nucleosome free energy, and rotational positioning of nucleosomes. Our model also indicates that the genomic regions underlying the MNase-sensitive nucleosomes in budding yeast have high deformation energy and, consequently, low nucleosome-forming ability, while the MNase-sensitive non-histone particles are characterized by much lower DNA deformation energy and high nucleosome preference. In addition, we also revealed that remodelers, SNF2 and RSC8, are likely to act in chromatin remodeling by binding to broad nucleosome-depleted regions that are intrinsically favorable for nucleosome positioning. Our data support the important role of position-dependent physical properties of DNA in nucleosome positioning.
aims: In this paper, we investigated the role of recombination on the evolution of the human genome based on high resolution recombination map and SNP data of 1000 Genomes Project from two aspects: How does recombination shape SNP-related genomic features? Whether recombination drives genome evolution through a neighbor-dependent mutational bias? background: Meiotic recombination (recombination for short) is a tightly regulated cellular process that occurs programmatically during meiosis in eukaryotic cells. The process involves a series of molecular events such as chromosome breaks, physical contact between homologous chromosomes, and the exchange of genetic information. The formation of crossover between homologous chromosomes during recombination is necessary for proper chromosome segregation, and the production of aneuploidy is closely associated with recombination abnormalities. Meiotic recombination not only plays an important role in gametogenesis by assisting chromosome segregation, but is also an important source of genetic variation. Recombination is capable of both inducing mutations and promoting gene conversion between homologous chromosomes. objective: Recombination promotes the efficiency of natural selection by disrupting genetic linkage and optimizing gene combinations. Although the role of recombination in genome evolution has been studied for many years, some factors such as the resolution of recombination map and the exact molecular mechanism of recombination have a great impact on the understanding of "recombination-mediated genome evolution ". method: 1. Based on the SNP data of 1000 Genomes Project (vcf files), by using tools such as VCFtools, SnpEff, and SNPsift in combination with programming calculations, we investigated the mutational bias, the composition of the alleles at SNP loci, allele frequency in the population, and their relationships with recombination rates. 2. Recombination-associated selection was tested by analyzing the ratio between nonsynonymous substitution rate and synonymous substitution rate, nucleotide diversity, Tajima's D, and heterozygosity at SNP loci. 3. Based on mutual information and conditional mutual information, we developed a method to quantitatively analyze the dependence of mutation on immediate adjacent bases (immediate neighbors) . result: Our results show that SNP density, Ts/Tv, nucleotide diversity and Tajima's D were positively correlated with recombination rate, while Ka/Ks was negatively correlated with the recombination rate. Moreover, compared with non-coding regions, gene exonic regions have lower nucleotide diversity but higher Tajima's D, suggesting that coding regions are subject to stronger negative selection but have fewer rare alleles. Gene set enrichment analysis of the protein-coding genes with extreme Ka/Ks ratio implicates that under the effect of high recombination rates, the genes involved in cell cycle, RNA processing, and oocyte meiosis are subject to strong negative selection. Our data also support S>W mutational bias and W>S fixation bias in high recombination regions. In addition, mutual information-based index was defined to measure the dependence of mutation at SNP sites on its neighbor bases, and the neighbor-dependent mutational bias was found to be stronger at high recombination regions. Specifically, if SNPs are flanked by A/G, C/G and C/T, the SNPs show stronger mutational bias at regions with high recombination rate, and if flanked by A/A, T/T and A/T, recombination antagonizes the mutational bias. conclusion: To conclude, based on the recombination map with the highest resolution available, we revealed some recombination-associated evolutionary patterns and selection at genome-wide level. Our results provided supporting evidence for the recombination-mediated GC-biased gene conversion and suggested the presence of C/G>T/A mutational bias during recombination.
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