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Simply by slowing down their metabolism, mutant fruit flies can go from zero to hero.
In a new study from Northwestern University, researchers slowed metabolic rates of mutant fruit flies by 50%, and the expected adverse effects of many mutations never occurred. After having experimentally tested numerous genetic mutations of fruit flies, the researchers obtained the same result each time.
"When flies thrived at a normal rate, development problems arose," said Richard Carthew, of the Northwest, who led the experimental research. "When we slow down, the developmental problems are gone, they grow more slowly and grow more slowly, but otherwise they are normal animals."
"This goes against the paradigm of everything we know about development," said Luís Amaral of the Northwest, who led the computer research. "We have always thought that if you" break "some genes, it would have serious developmental consequences, and it turns out that this is not the case for some genes, as long as you also slow down the metabolism. of the growing organism. "
The research could explain a number of factors, such as why factory reared chickens raised for excessive growth have more developmental problems or why caloric restriction is related to longevity.
The study is published in the journal Cell. Carthew is Professor of Molecular Bioscience at the Weinberg College of Science and Science in the Northwest and Professor of Biochemistry and Molecular Genetics at the Feinberg School of Medicine. Amaral is Professor Erastus O. Haven of Chemical and Biological Engineering at the McCormick School of Engineering, Northwestern.
Among the most striking discoveries of the study, researchers may have discovered that fruit flies, whose metabolism was slowed down, could live without microRNA, which was previously considered impossible. Present in all species of plants and animals, microRNAs play a key role in the regulation of gene expression. To put it simply: microRNAs control development, physiology and behavior.
"We know, after 20 years of research, that microRNAs are essential for life.If you did not have microRNA, you would be dead.It's as simple as that," Carthew said. "In our study, we slowed down the metabolism of fruit flies that did not produce microRNAs, survived, grew up, and became normal adults.
"Our result concludes that this whole family of gene regulators is not essential," he added. "All you have to do is slow down the metabolism by about 50%."
Nobel laureate, Thomas Hunt Morgan, first noted the link between diet and genetic mutations in 1915. When he raised mutant flies on limited amounts of bad food quality, Morgan noticed that some mutations had never been expressed.
"He thought it was interesting, but he had no explanation," Carthew said.
Carthew and Amaral now believe that the answer is control of feedback. Common in biology, engineering, economics and many other areas, feedback control allows complex systems to adjust performance to meet the desired response. After conducting hundreds of experiments over several years, the Northwestern duo believes that a slower metabolism gives animal systems time to correct errors.
"When you look at all the proteins and all the genes that interact within a cell, you can be overwhelmed by all the components and interactions between them," said Amaral. "If your growth is fast and something goes wrong, it can be catastrophic – you need these complex networks because they increase redundancy to avoid disasters.
"But if you grow slowly, you may not need such a complex system," he said. "You have more time to adapt to mistakes and to react to changes."
In other words, if you give the system more time, it will eventually get where it needs to be. Carthew, who is also a member of the Robert H. Lurie Cancer Research Center at Northwestern University, said the discovery could eventually be applied to cancer.
"Tumors are extremely metabolically active," he said. "Tumors absorb a huge amount of energy, so cancer patients are often exhausted, and we could think about ways to target cancer cell metabolism, perhaps by slowing down their metabolic rate." we could stop the oncogenic mutations expressing their cancer phenotype. "
Reference: Cbadidy et al. 2019. Repressive gene regulation synchronizes development with cellular metabolism. Cell. DOI: https://doi.org/10.1016/j.cell.2019.06.023.
This article has been republished from the following materials. Note: Content may have changed for length and content. For more information, please contact the cited source.
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