Zhu Xueting, Liu Shaochun, Ye Tiantian, Gu Xin, Pu Feiyu, Zhou Zhen, Wu Zhi-Jing, Zhou Jin-Qiu
Key Laboratory of RNA Innovation-Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
Interdisciplinary Research Center On Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 201210, China.
Genome Biol. 2025 Jul 29;26(1):229. doi: 10.1186/s13059-025-03689-1.
The genome of a eukaryotic cell is usually organized on a set of chromosomes. Recently, karyotype engineering has been applied to various organisms, but whether and to what extent a naturally evolved genome can resist or tolerate massive artificial manipulations remains unexplored.
Using unicellular yeast models of both Saccharomyces cerevisiae and Schizosaccharomyces pombe, we deliberately construct dozens of single-chromosome strains with different chromosome architectures. Three S. cerevisiae strains have the individual chromosomes fused into a single chromosome, but with the individual chromosomes in different orders. Eighteen S. cerevisiae strains have a single chromosome but with different centromeric sequences. Fifteen S. cerevisiae strains have a single chromosome with the centromere at different distances relative to the telomeres. Two S. pombe strains have a single, circular chromosome, and three strains have a single, linear chromosome with the centromere at different distances relative to the telomeres. All of these single-chromosome strains are viable, but the strains with an acrocentric or a telocentric chromosome have abnormal cell morphologies, and grow more slowly than those with a metacentric or sub-metacentric chromosome, and show increased genome instability with chromosome segregation abnormalities or genome diploidization.
The functional genomes of both the evolutionarily distant yeasts S. cerevisiae and S. pombe are highly tolerant of diversified genome organizations. The phenotypic abnormalities and increased genome instability of the acrocentric/telocentric single-chromosome yeasts suggest that yeasts with metacentric chromosomes have an evolutionary advantage.
真核细胞的基因组通常由一组染色体组成。最近，核型工程已应用于各种生物体，但自然进化的基因组是否以及在多大程度上能够抵抗或耐受大规模的人工操作仍未得到探索。
我们使用酿酒酵母和粟酒裂殖酵母的单细胞酵母模型，精心构建了数十种具有不同染色体结构的单染色体菌株。三种酿酒酵母菌株将单个染色体融合成一条单一染色体，但单个染色体的排列顺序不同。十八种酿酒酵母菌株具有一条单一染色体，但着丝粒序列不同。十五种酿酒酵母菌株具有一条单一染色体，其着丝粒相对于端粒的距离不同。两种粟酒裂殖酵母菌株具有一条单一的环状染色体，三种菌株具有一条单一的线性染色体，其着丝粒相对于端粒的距离不同。所有这些单染色体菌株都是可行的，但具有近端着丝粒或端着丝粒染色体的菌株具有异常的细胞形态，并且比具有中着丝粒或亚中着丝粒染色体的菌株生长得更慢，并且表现出基因组不稳定性增加，伴有染色体分离异常或基因组二倍体化。
进化距离较远的酿酒酵母和粟酒裂殖酵母的功能基因组对多样化的基因组组织具有高度耐受性。近端着丝粒/端着丝粒单染色体酵母的表型异常和基因组不稳定性增加表明，具有中着丝粒染色体的酵母具有进化优势。
