The human body is composed of trillions of cells, which perform countless tasks as members of different organ systems
However, cells are inevitably accumulating mutations
Peking University Biomedical Frontier Innovation Center (BIOPIC) researcher Bai Fan, Professor Huang Yanyi, Tsinghua University School of Life Sciences Researcher Wang Jianbin, Chinese Academy of Medical Sciences Peking Union Medical College Cancer Hospital Professor Wu Chen, and Academician Lin Dongxin are the co-corresponding authors of the research paper
Academician of the Academy of Sciences The Biomedical Frontier Innovation Center of Peking University reported in detail on this important achievement
After the technology was feasible, the research team conducted a systematic and in-depth study on samples from the same individual
The study first found that there are a large number of mutation accumulations in somatic cells of different normal tissues and organs, and the somatic mutation load and allelic mutation frequency show obvious organ differences
Unlike somatic mutations, gene copy number variations, especially large-scale genome copy number variations, seldom occur in various normal tissues, and the occurrence of copy number variations has a certain organ preference
Next, the research team analyzed the potential driving reasons for the accumulation of a large number of somatic mutations in different normal tissues by analyzing the characteristics of single-base mutations, and resolved a total of 7 different mutation characteristics
Interestingly, the two mutation characteristics of SBS1 and SBS5 have obvious organ specificity in the relative contribution ratio of somatic mutation accumulation in various normal tissues
In addition, it is worth noting that two mutation features related to exogenous mutagenic factors, SBS4 (related to smoking) and SBS22 (related to the mutagen aristolochic acid) mainly appear in liver tissues, which reveals the exogenous environment The inducing effect of factors on the accumulation of somatic mutations in normal human tissues also reflects that liver tissue has a higher risk of being mutagenized by environmental factors
The research team further discovered that even between adjacent samples in the same individual and the same tissue, the mutation characteristics can have obvious heterogeneity, which reflects the activity of various internal and external mutagenic factors in normal tissues.
Through further mining of the data, the research team also analyzed cancer-related "driver gene" mutations accumulated in various normal tissues, and found a total of 32 mutated "driver genes", including NOTCH1, TP53, ARID1A And ERBB2 are widely recognized genes related to tumorigenesis
In the end, they also constructed a map of mutant clone space expansion with sub-millimeter resolution, and found that mutant clones in normal esophagus may expand to near millimeter level, which is potentially related to the extensive accumulation of "driver gene" mutations and copy number variation in the esophagus
The research team believes that these results indicate that the expansion and evolution of somatic mutant clones in different tissues and organs will be promoted or restricted by a variety of factors
It is worth mentioning that in addition to the research from the Chinese team, Nature published three other research papers on somatic mutations from the Wellcome Sanger Institute, the University of Cambridge, and the Korean Institute of Science and Technology (KAIST) at the same time
Nature also published an opinion review article written by Kamila Naxerova of the Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School
.
Naxerova concluded that what the four studies published at the same time have in common is that they use genomic mutations as markers to trace their pedigrees
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The mutation characteristics of a cell are like fingerprints.
By sequencing the genomes of cells in different parts of the body, ancestor relationships can be determined and a cell "family tree" can be constructed, so that the origin and history of the cell can be reviewed
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Naxerova commented that these four studies together provide an impressive proof of the power of modern genetics to decipher cell dynamics
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Larger studies of this kind will help to understand how organs are formed and, most importantly, will deepen our understanding of diseases caused by harmful mutations that sometimes occur during embryonic development
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Links to related papers:
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