Yun Wang:
|
Understanding the occurrence and development of complex phenotypes has always been a challenge for biological scientists. Saccharomyces cerevisiae is an important eukaryotic model widely used to study the molecular mechanisms of various phenotypes.
In recent decades, by the rapid development of synthetic genomics technologies, the synthetic S. cerevisiae genome (Sc2.0) has generated a series of synthetic yeast strains with the artificial designer chromosomes. As a distinctive feature of the Sc2.0 genome, the SCRaMbLE (Synthetic chromosome rearrangement and modification by loxP-mediated evolution) system could generate a massive genomic diversity and stochastically boost extrachromosomal circular DNAs (eccDNAs) by combinatorial rearrangement at the designed loxPsym site in synthetic chromosomes.
In recent studies, the SCRaMbLE of synthetic chromosomes, as an efficient evolutionary tool for genome shuffling, has exhibited a great versatility in metabolic engineering for strain improvement of the production field and stress tolerance. This PhD thesis aims to dissect host cells’ molecular mechanism and adaptability by SCRaMbLEing synthetic yeast.
The thesis consists of three main research objectives, where the first and second research works focus on the molecular genetic mechanism of aneuploidy phenotypes and replicative aging, respectively. The third work elucidates the roles of extrachromosomal circular DNAs (eccDNAs) on inheritance and adaptability.
Overall, the results demonstrate the SCRaMbLE of synthetic chromosomes as an efficient and effective evolutionary research strategy to dissect host phenotypes in yeast. It is foreseeable that the completion of all Sc2.0 yeast chromosomes, or the prospect of de novo assembly of chromosomes from other species, including humans, would open a new era of research in synthetic genomics.