Ren Peijun, Dong Xiao, Vijg Jan
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Genetics, Cell Biology and Development, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United States.
Front Aging. 2022 Sep 21;3:1018119. doi: 10.3389/fragi.2022.1018119. eCollection 2022.
The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.
多细胞生物的基因组携带着发育所有器官和组织以及在成年期维持功能所需的遗传信息。为确保物种的遗传稳定性，基因组受到保护以防序列信息发生变化。然而，基因组并非静止不变。生殖细胞中的突变会传递给后代，并在进化过程中产生所需的变异。此外，合子后突变在发育和衰老过程中发生于所有体细胞中。这些体细胞突变仅限于个体，产生基因组镶嵌的组织。由于其丰度极低，对这类突变及其后果的了解一直有限，大多数突变在每个细胞中都是独特的。测序技术的最新进展，包括单细胞水平的全基因组测序，现已首次让我们了解到人类组织中的体细胞突变负担。在此，我们将首先简要描述体细胞突变分析的最新方法，然后回顾我们目前对人类组织中体细胞突变负担的认识，最后简要讨论体细胞突变对衰老过程和与年龄相关疾病（包括癌症和非癌症疾病）可能产生的功能影响。
