Mitochondrial DNA: How do mothers affect children’s height and lifespan?
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Mitochondrial DNA: How do mothers affect their children’s height and lifespan?
Mitochondrial DNA: How do mothers affect their children’s height and lifespan? Cambridge scientists find new evidence, or hope to help future generations grow taller and live longer.
Recently, researchers from the University of Cambridge analyzed the biological data of 350,000 people and found that the mother’s mitochondrial DNA mutation is closely related to the increased risk of many common diseases such as type 2 diabetes and multiple sclerosis in the offspring. At the same time, the mother’s mitochondrial DNA will also affect the height and lifespan of the offspring.
The study was titled “An atlas of mitochondrial DNA genotype–phenotype associations in the UK Biobank” and was published in the latest issue of Nature Genetics, Professor Patrick F. Chinnery, Department of Clinical Neuroscience, University of Cambridge, and Department of Public Health and Primary Care Professor Joanna MM Howson co-led the research.
Regarding this research, Professor Howson said, “Except for mitochondrial diseases, we usually do not associate mitochondrial DNA mutations with common diseases. But now we have shown that human mitochondrial DNA inherited from mothers affects the risk of some diseases, such as Type 2 diabetes, multiple sclerosis, abdominal aortic aneurysm, etc.”
Human Mitochondrial DNA and Disease
As we all know, almost all the genetic material that constitutes the human genome is stored in the cell nucleus. The DNA in the cell nucleus encodes different proteins so that humans have different characteristics and assist the human body in accomplishing different tasks.
The mitochondria in the cell mainly provide energy for the cell, and the mitochondria realize the purpose of supplying energy for the cell by converting nutrients such as glucose into ATP. At the same time, mitochondria also contain a very small amount of DNA, which is called mitochondrial DNA. Its content accounts for only 0.1% of the human genome, and it can only be passed on to offspring through mothers.
The structure of the human mitochondrial genome is very compact, consisting of only 16,569 base pairs, of which about 95% of the DNA sequence is used to encode 13 proteins, 22 transfer RNAs, and 2 ribosomal RNAs. These substances are mitochondrial oxidative phosphorylation and ATP. Substances necessary for production. Previous studies have shown that although mitochondrial DNA only accounts for 0.1% of the human genome, its abnormality may still cause some serious diseases.
Mitochondrial diseases are due to various reasons that cause gene mutations in mitochondrial DNA or nuclear DNA, which make mitochondrial enzyme function defects, ATP synthesis obstacles, and the inability to maintain the normal physiological functions of cells to produce oxidative stress, increase the production of oxygen free radicals, and induce cell apoptosis. Die. Some mitochondrial diseases only affect a single organ. For example, leber hereditary optic neuropathy only affects the eyes, but common mitochondrial diseases often involve multiple organs, and most of them show muscle and neuropathy.
Mitochondrial diseases can occur at any age. Mitochondrial diseases caused by nuclear gene mutations mostly occur in childhood, while mitochondrial diseases caused by mitochondrial DNA usually occur in late childhood or adulthood. Its genetic characteristics are manifested as non-Mendelian inheritance, also known as extranuclear inheritance.
At present, people have clearly known that mitochondrial DNA mutations can induce some rare diseases, which can lead to severe disabilities, such as MELAS syndrome, myoclonic epilepsy with broken red fibers, Leber hereditary optic neuropathy, and mitochondrial DNA deletion syndrome, etc. . However, for some common diseases, such as type 2 diabetes, liver and kidney dysfunction, etc., although some small studies have found that mitochondrial DNA is related to it, people cannot replicate their findings, and the evidence is not complete.
Large-scale mitochondrial DNA-trait association research
In the view of researchers at the University of Cambridge, people have not yet discovered the association between mitochondrial DNA variation and common diseases. The main reason is that the etiology of common diseases is more complicated, and people have insufficient ability to study the association between complex traits and mitochondrial DNA. Therefore, although some scholars have conducted research on the relationship between mitochondrial DNA and common diseases, they often draw conflicting conclusions, and the research is difficult to repeat.
In order to overcome this obstacle, the Cambridge University research team has developed a new model to study the relationship between mitochondrial DNA and human disease characteristics, and systematically analyzed the biological data of 358,000 volunteers in the British biological database.
The results found that mitochondrial DNA not only causes some rare diseases, but also has significant effects on common human diseases and characteristics such as type 2 diabetes, multiple sclerosis, liver and kidney function, abdominal aortic aneurysm, blood cell count, life span, and height. In fact, in this experiment, the researchers discovered a total of 260 new mitochondrial DNA-related phenotypes.
There are several possible explanations for the impact of mitochondrial DNA on human diseases. One is the difference in energy production caused by the changes in mitochondrial DNA mentioned earlier. But the research team prefers a more complex explanation, that is, mitochondrial DNA variation not only affects energy production, but also affects the body’s complex biological pathways.
Generally speaking, half of the nuclear DNA of the offspring comes from the father and half from the mother, while the mitochondrial DNA is inherited entirely from the mother. This indicates that there should be independent inheritance between nuclear DNA and mitochondrial DNA, and there is no correlation between the two. However, in experiments, researchers found that the genetics of the two are clearly related, that is to say, mitochondrial DNA and nuclear DNA interact with each other and evolve continuously.
For example, ATP is produced by a group of proteins in the mitochondria. More than 100 proteins are involved in the entire ATP production process, of which 13 are encoded by mitochondrial DNA, and the rest are encoded by nuclear DNA. Therefore, the proteins in the ATP production process are actually produced by two different genomes, and they need to cooperate with each other in the cell.
Obviously, if the offspring inherited from the mother’s mitochondrial DNA and the father’s nuclear DNA are incompatible, then the production of mitochondrial ATP will definitely be affected, which may slowly but lastingly affect a person’s health and physiological condition. From an evolutionary perspective, this process is clearly unfavorable. Conversely, evolution may encourage more matching unions, which are healthier, live longer, and have an advantage in survival.
In recent years, mitochondrial transplantation therapy has gradually developed into a hot technology that allows scientists to replace defective mothers with mitochondria from donor mothers, thereby preventing their offspring from suffering from life-threatening mitochondrial diseases.
In this regard, Professor Chinnery, the corresponding author of this article, said, “It seems that our mitochondrial DNA matches our nuclear DNA to some extent. We can’t exchange mitochondrial DNA at will, just like we can’t do blood transfusion. Fortunately, at present Research teams have been exploring the feasibility of mitochondrial transplantation therapy.”
In general, this research has discovered for the first time the key role of mitochondrial DNA in a variety of common human diseases, which is essential for helping humans understand the genetic structure of mitochondria and the interaction with nuclear genetic material. The set of mitochondrial DNA mutation characteristics and related phenotypes provided in this study also lays the foundation for future mitochondrial genome research.
(source:internet, reference only)
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