Vijg Jan, Dong Xiao, Milholland Brandon, Zhang Lei
Department of Genetics, Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461, U.S.A.
Essays Biochem. 2017 Jul 11;61(3):305-315. doi: 10.1042/EBC20160082. Print 2017 Jul 15.
DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals. More recently, next-generation sequencing-based methods have been developed to accurately determine the complete landscape of base substitution mutations in single cells. The first results show that the somatic mutation rate is much higher than the germline mutation rate and that base substitution loads in somatic cells are high enough to potentially affect cellular function.
DNA是遗传信息的载体,也是所有细胞信息最终来源的主要模板。通过突变改变DNA信息内容会通过自然选择产生进化的多样性,但也是有害影响的一个来源。长期以来,人们一直推测多细胞生物体体细胞中的突变积累可能会导致与年龄相关的细胞退化和死亡。检测从碱基替换到大型染色体畸变等不同类型突变的方法已经开发出来,并且明确显示突变在衰老人类和动物的不同组织和细胞类型中积累。最近,基于下一代测序的方法已经开发出来,以准确确定单细胞中碱基替换突变的完整情况。首批结果表明,体细胞突变率远高于种系突变率,体细胞中的碱基替换负荷高到足以潜在地影响细胞功能。