Were ‘jumping genes’ found to alter human colon genomes, offering insights into aging and tumorigenesis? — Daily Science

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With approximately 500,000 L1 jumper genes, representing 17% of the human genome, they have long been recognized for their contribution to the evolution of the human species by introducing “disruptive innovation” into genome sequences. Until now, it was believed that most L1 elements had lost their ability to jump in the normal tissues of modern humans. However, this study reveals that some L1 hopping genes can be extensively activated in normal cells, leading to the accumulation of genomic mutations throughout an individual’s lifetime. The L1 hopping rate and the resulting genomic changes vary between different cell types, with a notable concentration being observed in aged colonic epithelial cells. The study illustrates that each colonic epithelial cell experiences an L1 skipping event at the age of 40 on average.

The research, led by co-authors Chang Hyun Nam (KAIST graduate student) and Dr. Jeonghwan Youk (former KAIST graduate student and clinical assistant professor at Seoul National University Hospital), involved sequence analysis of the complete genome of 899 individual cells obtained from skin (fibroblasts), blood, and colon epithelial tissues collected from 28 individuals. The study uncovers the activation of L1 hopping genes in normal cells, resulting in the gradual accumulation of genomic mutations over time. In addition, the team explored epigenomic sequences (DNA methylation) to understand the mechanism behind the activation of the L1 jumper gene. They found that cells with activated L1 jumping genes exhibit epigenetic instability, suggesting the critical role of epigenetic changes in regulating L1 jumping gene activity. Most of these epigenomic instabilities were found to arise during the early stages of embryogenesis. The study provides valuable information on the aging process and disease development in human colorectal tissues.

“This study illustrates that genomic damage in normal cells is acquired not only through exposure to carcinogens but also through the activity of endogenous components whose impact was previously unclear. The genomes of apparently healthy aging cells, particularly in colorectal epithelium, become mosaic due to the activity of L1 hopping genes,” said KAIST Professor Young Seok Ju.

“We stress the essential and ongoing collaboration between researchers in clinical medicine and basic medical sciences,” said Prof. Min Jung Kim from the Department of Surgery at Seoul National University Hospital. “This case highlights the critical role of systematically collected human tissues from clinical settings in unraveling the complex process of disease development in humans.”

“I am delighted that the research team’s breakthroughs in single-cell genome technology have come true. We will persistently strive to lead single-cell genome technology,” said Professor Hyun Woo Kwon, from the University College’s Department of Nuclear Medicine. from Korea. of Medicine.

The research team was supported by the National Research Foundation of Korea Research Leaders Program and Young Investigators Program, a Physician Scientist/MD-PhD Training Program grant through the Industry Development Institute. of Korea Health and the Suh Kyungbae Foundation.