Nature+Genetics
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Unraveling Mitochondrial DNA Mutations in Human Cells
Throughout our lifetime, cells accumulate DNA mutations, which contribute to genetic diversity, or “mosaicism”, among cells. These genomic mutations are pivotal for the aging process and the onset of various diseases, including cancer. Mitochondria, essential cellular organelles involved in energy metabolism and apoptosis, possess their own DNA, which are susceptible to mutations. However, studies on mtDNA mutations and mosaicism have been limited due to a variety of technical challenges.
Genomic scientists from KAIST have revealed the genetic mosaicism characterized by variations in mitochondrial DNA (mtDNA) across normal human cells. This study provides fundamental insights into understanding human aging and disease onset mechanisms.
The study, “Mitochondrial DNA mosaicism in normal human somatic cells,” was published in Nature Genetics on July 22. It was led by graduate student Jisong An under the supervision of Professor Young Seok Ju from the Graduate School of Medical Science and Engineering.
Researchers from Seoul National University College of Medicine, Yonsei University College of Medicine, Korea University College of Medicine, Washington University School of Medicine National Cancer Center, Seoul National University Hospital, Gangnam Severance Hospital and KAIST faculty startup company Inocras Inc. also participated in this study.
< Figure 1. a. Flow of experiment. b. Schematic diagram illustrating the origin and dynamics of mtDNA alterations across a lifetime. >
The study involved a bioinformatic analysis of whole-genome sequences from 2,096 single cells obtained from normal human colorectal epithelial tissue, fibroblasts, and blood collected from 31 individuals. The study highlights an average of three significant mtDNA differences between cells, with approximately 6% of these variations confirmed to be inherited as heteroplasmy from the mother.
Moreover, mutations significantly increased during tumorigenesis, with some mutations contributing to instability in mitochondrial RNA. Based on these findings, the study illustrates a computational model that comprehensively elucidates the evolution of mitochondria from embryonic development to aging and tumorigenesis.
This study systematically reveals the mechanisms behind mitochondrial DNA mosaicism in normal human cells, establishing a crucial foundation for understanding the impact of mtDNA on aging and disease onset.
Professor Ju remarked, “By systematically utilizing whole-genome big data, we can illuminate previously unknown phenomena in life sciences.” He emphasized the significance of the study, adding, “For the first time, we have established a method to systematically understand mitochondrial DNA changes occurring during human embryonic development, aging, and cancer development.”
This work was supported by the National Research Foundation of Korea and the Suh Kyungbae Foundation.
2024.07.24 View 1834 -
Gene Protecting Brain Nerves Discovered
THE KOREA TIMES 2005.1.31By Kim Tae-gyu / Staff Reporter
South Korean scientists have for the first time discovered genes tasked with protecting brain nerves.
Korea Advanced Institute of Science and Technology professor Kim Jae-seob said Sunday the new genes, named pyrexia, shield brain nerves from outside stimuli, including high temperatures.
``The channel gene of pyrexia will open the door to developing new-concept medicines for brain damage in patients of high fever or drug addicts,’’ he said.
The channel gene refers to transport proteins, which provide a static passageway for a variety of essential substances to enter into cells.
``Up until now, a lot of channel genes activated by temperatures have been identified. But among them, pyrexia is first that guards brain nerves from external stresses,’’ Kim said.
Kim’s team learned pyrexia plays a pivotal role in the body through experiments with genetically engineered flies that did not have any pyrexia.
Up to 60 percent of the pyrexia-depleted mutants were paralyzed within three minutes of exposure to a temperature of 40 degrees Celsius.
In comparison, just 9 percent of normal flies were paralyzed with the same stimulus, indicating pyrexia is responsible for protecting animals from high-temperature stress.
``Our next goal is to develop pyrexia-embedded drugs, which can be expected to commercially debut in about five years,’’ Kim said.
Kim has already applied for international patents for his medical breakthrough, which will be printed in the March edition of Nature Genetics, a science journal.
voc200@koreatimes.co.kr
2005.02.02 View 13950 -
Nerve-protecting gene discovered
Korean scientists for the first time have identified a gene that blocks nerve damage from fevers and the use of narcotics, a state-run research institute said yesterday.
The finding may open the way for new medicine that can prevent the loss of brain function which is frequently caused by excessive stimulation of nerves and abnormally high body temperature.
"The research is in an early stage. But this approach has the potential to develop genetics-based preventatives against brain-attacking diseases," said Kim Jae-seob, a bioscience professor of the Korea Advanced Institute of Science and Technology, who led the study.
The researchers named the gene Pyrexia, which means fever. Kim"s team extracted it from genetically engineered fruit flies using a genome-screening system. In laboratory tests, they found that the gene is activated to 39 degrees Celsius or higher.
The researchers enhanced Pyrexia"s functionality in some fruit flies while removing the gene from others to observe their different reactions when exposed to high temperature.
"The fruit flies without the gene showed severe nerve disorder and suffered paralysis of brain function, while Pyrexia-enhanced flies maintained their normal brain conditions," the professor said.
The researchers got the same result from experiments with human cells, he said.
There are a lot of channel proteins, which enable ions to enter and exit the cell, that react to the level of temperature, but Pyrexia is the first of its kind that actually protects the neurons from external stimulus, he said.
The finding will appear on the March edition of the London-based science magazine Nature Genetics.
THE KOREA HERALD 2005.1.31 (thkim@heraldm.com) By Kim Tong-hyung
2005.02.02 View 13810