Loss of heterozygosity by SCRaMbLEing  

作　　者：Yunxiang Li Yi Wu Lu Ma Zhou Guo Wenhai Xiao Yingjin Yuan 

机构地区：[1]Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University [2]Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University

出　　处：《Science China(Life Sciences)》2019年第3期381-393,共13页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (21621004, 21750001 and 21676192);Young Elite Scientist Sponsorship Program by CAST (YESS) (2018QNRC001)

摘　　要：Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE,different levels of loss of heterozygosity(LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome Ⅹ, whole chromosome LOH of synthetic chromosome Ⅹ, and duplication of chromosome Ⅷ(trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE,different levels of loss of heterozygosity(LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome Ⅹ, whole chromosome LOH of synthetic chromosome Ⅹ, and duplication of chromosome Ⅷ(trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.

关 键 词：SCRAMBLE loss of heterozygosity(LOH) rapid adaptive evolution ANEUPLOIDY structural variation synthetic YEAST GENOME 

分 类 号：Q[生物学]