Identification of genes involved in aging and carcinogenesis
Regarded as junk DNA, the L1 jumping gene can control aging and disease occurrence once suppressed
image: a, Experimental design of the study. HSC, haematopoietic stem and progenitor cells. b, Proportion of clones with various numbers of soL1Rs across different cell types (number of clones shown in parentheses). c, Proportion of normal colorectal clones with various numbers of soL1Rs across 19 individuals (number of clones shown in parentheses). d, Linear regression of the average number of soL1Rs per clone on age in 19 individuals with normal colorectal clones. Vertical line crossing each dot indicates the range of soL1R burden per clone in each individual. Blue line represents the regression line, and shaded areas indicate its 95% confidence interval. Two outlier individuals (HC15 and HC06) are highlighted in red. e,f, Early clonal phylogenies of HC14 (e) and HC19 (f) reconstructed by somatic point mutation. Branch lengths are proportional to the numbers of somatic mutations, which are shown by numbers next to the branches. Early embryonic branches are coloured by variant allele fraction (VAF) of early embryonic mutations (EEMs) in the blood. The numbers of soL1Rs detected are shown in the filled circles at the tips of branches. Pie charts indicate the proportion of blood cells harbouring the EEM or soL1R. RT segment, retrotransposed segment. g, Normalized soL1R rates in various stages and cell types.
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Professor Hyun Woo Kwon of the Department of Nuclear Medicine, Korea University’s College of Medicine, and his research team research(joint research by Professor Young Seok Ju of KAIST, Professor Min Jung Kim of Seoul National University Hospital) identified genes involved in aging and carcinogenesis.
99% of human genome are not clearly identified with their functions. These are called “junk DNA” due to uselessness. “The L1 jumping genes,” which take around 1/6 of junk DNA, had been known to promote occurrence of cancer and other diseases, but inactivated in the process of evolution.
The research team used bioinformatic techniques to analyze the whole-genome sequencing of 899 single cells obtained from the skin, blood, and some tissues of the colorectal epithelium of 28 people. As a result, the team found activation of the L1 jumping gene present in some colorectal epithelium.
This activation was higher in the colorectal epithelial cells of elderly than in the young population. It was discovered that colorectal epithelial cells have one or more retrotransposition of the L1 jumping gene in the age of 40, which can affect the occurrence of diseases such as colorectal cancer.
The research team discovered epigenetic genome instability in cells with the activated L1 jumping genes through epigenetic studies. It was found that this phenomenon occurs throughout the entire life from the time of fertilization and the formation of large intestine and rectum. This confirms that changes in epigenetic genomes are the switch controlling the activation of L1 jumping gene.
Professor Hyun Woo Kwon said “we expect to develop a technique of controlling human aging and disease occurrence if we can suppress the activation of L1 jumping gene.” Further adding, “We will continue our best efforts to lead the single cell genome technology in the future.”
This study of “Widespread somatic L1 retrotransposition in normal colorectal epithelium” was published in the international journal of “Nature (Impact factor 69.5)”