针对我们在单细胞真核模式生物嗜热四膜虫中发现的有性生殖突变率显著高于无性生殖突变率的结果，本项目利用其一个细胞中同时具有germline小核和somatic大核、生活史中同时存在有性生殖和无性生殖的特点，运用实验进化基因组学的研究方法，对嗜热四膜虫生活史不同阶段的大、小核基因组进行高通量的重测序，在发展和建立适合四膜虫的溯祖理论和统计方法的基础上，测定和计算嗜热四膜虫生活史各阶段的突变量和突变率，鉴定有性生殖高突变率产生的具体阶段并对相关过程中关键基因进行结构和功能进化分析，进而阐明有性生殖高突变率的分子机理，探讨突变率在有性生殖适应性优势和生殖方式进化中的驱动作用。项目的开展将开辟四膜虫群体遗传学研究新领域，将是对现有生殖进化理论的重要补充和完善，将推动四膜虫基础生物学的发展，也将对研究人类个体内细胞谱系的演化（包括肿瘤和癌细胞演变）具有借鉴价值。

Focusing on the question that the mutation rate of sexual reproduction is much higher than that of asexual reproduction in the unicellular eukaryotic model organism -- Tetrahymena thermophila, considering its advantages (with germline micronucleus, MIC and somatic macronucleus, MAC in one cell; and sexual and asexual stages during its life cycle), we sequence the Mic and Mac genomes during continuous stages of its life cycle, and develop coalescent based population genetic models and simulation algorithms for Tetrahymena to estimate the mutation rate at different stages, and identify the specific sexual stage arising high mutation rate and study the molecular evolution of involved genes in this stage, and then reveal the molecular mechanism of high mutation rate of sexual reproduction, finally discuss the possible driving force of mutation rate on the adaptative advantage of sexual reproduction and the evolution of reproduction. The completion of project will open new field of Tetrahymena population genetics, and complement and improve the theory of reproduction evolution, and develop the fundamental biology of Tetrahymena, and use for reference to study the evolution of cell lineage (including tumour and cancer cells) within human individual.