Professor Yeong-seok Ju from the Graduate School of Medical Science has made groundbreaking research regarding the function and impact of “Junk DNA” on human aging and cancer development. The research was featured in Nature Communications under the title “Widespread somatic L1 retrotransposition in normal colorectal epithelium” on May 10.
Our understanding of the human genome has traditionally been that it consists of roughly 1% of standard protein-creating genes, while the remaining 99% has often been referred to as “Junk DNA”, given the ambiguity surrounding its functions. Among this “Junk DNA”, the “L1 jumping gene”, taking up about a sixth of the junk DNA, was believed to have been deactivated over the course of human evolution due to its potential to disrupt or even destroy cellular genetic information if activated.
Contrary to the prevailing understanding, the research revealed that the L1 jumping gene can still be activated in certain tissues, and it is often responsible for frequent genomic mutations during the aging process. This discovery provides an entirely new lens through which to view cellular aging and cancer progression.
The team analyzed the full genome sequence of 899 single cells obtained from the skin, blood, and colorectal epithelial tissues of 28 individuals. They found the rate of mutations caused by the L1 jumping gene varied markedly between cell types, predominantly surfacing in older colorectal epithelial cells. Furthermore, the team uncovered that such genomic mutations in colorectal epithelial cells occur consistently throughout an individual’s life, starting from the embryonic development stage. According to the findings, by the age of 40, individuals’ colorectal epithelial cells will likely carry more than one mutation instigated by the L1 jumping gene.
To trace the activation mechanism of L1 jumping genes, researchers also examined DNA methylation, an epigenetic mechanism. They found that epigenetic instability, which was discovered in cells where L1 jumping genes were activated, could act as a “switch” controlling their activity. The majority of this instability was shown to form during the early stages of embryonic development.
This research sets the foundation for future studies, potentially leading to novel diagnostic techniques or disease risk predictions. The findings could open doors for interventions that could slow aging or prevent age-related diseases, and influence prenatal diagnosis and treatment.