Analysis Of The Isochore Structures And Ultraconserved Sequences Of The Human And Other Eukaryotic Genomes

With the development of the sequencing technology, the whole genomic sequences of numerous organisms have become publicly available. It gave us an unprecedented opportunity to analyze the features of genome organizations at sequence level and to study differences among organisms by comparing the whole genomic sequences. Previous research works have revealed many basic features of the genome organizational structures. In this thesis, the isochore structures and ultraconserved sequences of human and other eukaryotic genomes were analyzed.The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores, which have been linked to many important functions. Biological implications of most isochore boundaries, however, remain elusive, partly due to the difficulty in determining these boundaries at high resolution. Using the segmentation algorithm based on the quadratic divergence, we re-determined all 79 boundaries of previously identified human isochores at single-nucleotide resolution, and then compared the boundary coordinates with other genome features. We found that 55.7% of isochore boundaries coincide with termini of repeat elements; 45.6% of isochore boundaries coincide with termini of highly conserved sequences based on alignment of 17 vertebrate genomes, i.e., the highly conserved genome sequence switches to a less or non-conserved one at the isochore boundary; some isochore boundaries coincide with abrupt change of CpG island distribution (note that one boundary can associate with more than one genome feature). In addition, sequences around isochore boundaries are highly conserved. These results suggest possible key roles of the isochore boundaries and may further our understanding of the human genome organization. By the analysis of the whole genomes of human, mouse, cow, zebrafish, tetraodon and poplar, we have found that all the genomes are composed of isochores. They share some common characters, but in some aspects they differ from each other. The features of isochores in the poplar genome are obviously different from others. The discovery of the ultraconserved elements in the human genome has caused wide attentions. The ultraconserved elements in insect genomes have also been studied. But the instance of the ultraconserved sequences in the plant genomes remains untouched. In this thesis we found 33 independent ultraconserved segments which are absolutely conserved between A. thaliana and rice genomes. Many problems about these ultraconserved sequences have been analyzed, such as lengths of the ultraconserved sequences, the total number of them, the sequence features, the genetic functions, and the sequence similarities with other plant genomes.