Genome remodeling during adaptive evolution

描述（由申请人提供）：基因组不稳定性，如非整倍性、缺失、扩增和易位，可在适应性进化过程中为异常细胞带来生长优势。已经提出，与这些类型的基因组重排相关的不稳定性和适应性优势在许多类型的癌症的早期阶段是重要的。在物种形成过程中，类似的机制可能导致新物种的建立，其中基因组重排可能产生选择性适应性优势，从而产生新的基因组互补物。导致上述基因组重排的机制及其在适应性进化过程中的作用将使用酵母菌的杂交生物进行研究。具体而言，将对杂交酵母物种形成过程中发生的染色体重排进行详细表征，并将鉴定酵母属物种之间的潜在基因不相容性。此外，将研究这些杂交酵母在特定环境压力下的基因组重排和稳定性。这些特定目标的结果将提供对适应性进化中基因组重排的重要性的见解，并适用于癌症的进展。 癌症的进展被比作新物种的出现过程。了解新物种形成的机制以及它们在特定条件下的稳定性，将进一步加深我们对物种形成过程的认识。这些知识可以扩展到癌症的进展，因此将对疾病的治疗产生潜在的影响。

DESCRIPTION (provided by applicant): Genomic instability such as aneuploidies, deletions, amplifications, and translocations, can give rise to growth advantages for an abnormal cell during adaptive evolution. It has been proposed that the instability and fitness advantage associated with these types of genomic rearrangements are important in the early stages of many types of cancer. Similar mechanisms can potentially lead to the establishment of new species during the process of speciation, where genomic rearrangements can potentially yield selective fitness advantage leading to novel genome complements. The mechanisms that lead to genome rearrangements described above and their role during adaptive evolution will be investigated using hybrid organisms of the yeast, Saccharomyces. Specifically, a detailed characterization of the chromosomal rearrangements that occur during speciation of hybrid yeasts will be performed and potential genie incompatibilities between Saccharomyces species will be identified. In addition, the genomic rearrangements and stability of these hybrid yeasts under specific environmental pressures will be investigated. Results from these specific aims will provide insights into the importance of genome rearrangements in adaptive evolution with applicability to the progression of cancer. The progression of cancer has been likened to the process of emergence of new species. Understanding the mechanisms governing how new species are formed and their stability under specific conditions will further our knowledge of the process of speciation. This knowledge can be extended to the progression of cancer, and will thus have potential impact on treatment of the disease.