高等植物基因组的精细结构，是研究功能基因以及分子机制的基础。棉花细胞染色体端粒以及基因组中富含G的序列在测序过程中PCR扩增效率远低于随机序列，导致在序列组装时产生大量的gap。本项目结合化学与生物学的方法，可能对富含G序列分离测序从而实现棉花基因组的精细结构。化学合成生物素标记的有机小分子(PDP-PEG-Biotin)，特异性的识别棉花基因组中富含G的序列，由链酶亲和素磁珠分离富集，并进行第三代SMRT测序。再将富含G的序列组装拼接到棉花基因组草图，得到棉花基因组精细结构，进而解析隐匿在端粒区的功能基因。本项目基于基因组DNA的二级结构，应用化学小分子将测序中扩增效率低的片段分离富集，从而实现棉花基因组的精细结构。化学小分子辅助测序手段的加入，可能大大提高动植物基因组的解析度，提高大基因组测序组装的完整性和准确度。

High-quality genome sequences and accurate gene annotations of higher plants are the basis for investigation of plant gene functions and molecule mechanism of cell development. Telomeres of cotton chromosomes and other G-rich sequences in cotton genomes are hard to be sequenced and assembled because of low amplification efficiency in the PCR processes, resulting in large numbers of gaps in genome sequences. In this study, we will employ interdisciplinary principles and methods to resolve the G-rich sequence issue based on chemistry and biology. Pyridostatin type small molecules (PDP/PDS) are synthesized and labeled by biotin, with a long PEG linker in the bifunctional compound to reduce the steric hindrance. G-rich sequences in cotton genome could be specifically bound by PDP/PDS, and the complexes could be captured and enriched by streptavidin beads. The purified DNA with G-rich sequences is sequenced by Single Molecule Real-Time (SMRT) technology and data are assembled with reference genome. The functional genes buried in telomere region could be dissected with the high-quality genome. The significant advantage of this strategy is the application of small molecules to assist with high-quality genome sequencing and assembly, and this strategy could be used in other genome assembly with much higher resolution and much lower cost.