February 28, 2020
29/02/2020
February 28, 2020
JUPITER, FL A set of molecules needed for efficient energy production in cells apparently underwent a radical change during early animal evolution so they could continue to function despite their relatively high mutation rate, according to a new study from scientists at Scripps Research.
In the study, published in Nature Communications, the scientists analyzed a set of 22 closely related mitochondrial molecules. Mitochondria are tiny, bacteria-like organelles that are the major producers of chemical energy in cells; they contain their own small DNA genomes, which are separate from the main genome in the cell nucleus. The 22 mitochondrial molecules, called mitochondrial transfer RNAs (mt-tRNAs), play a central role in translating the information in mitochondrial genes into mitochondrial proteins.
The researchers found evidence that as more complex animals evolved from the simplest ones, their mt-tRNAs evolved to have an unusual basic structure, which conferred a remarkable capacity to keep working properly despite frequent mutations to their genes. Mitochondrial DNA is more vulnerable to mutations, especially in complex animals.
The mutational freedom of these novel mt-tRNA structures appears to be a powerful adaptive mechanism for withstanding the enhanced mutation rate of mitochondrial DNA in higher animals, says senior author Paul Schimmel, PhD, a professor in the Department of Molecular Medicine at Scripps Research.
Mitochondria are found in numbers up to thousands per cell in virtually all plants and animals, as well as in many simpler organisms. Theyre widely believed to have originated as bacteria that could live symbiotically inside the cells of some early, simple life forms. But after hundreds of millions of years of evolution, they have become essential producers of chemical energy in all complex species. They use oxygen to produce this energy and that need for oxygen is why animals breathe.
One of the problems with mitochondria, from a human health perspective, is that they are especially vulnerable to damage. Mitochondria contain their own circular DNA genomes, which in humans encode 37 mitochondrial molecules including the 22 mt-tRNAs. Compared with ordinary DNA in the cell nucleus, mitochondrial DNA is not as well protected from DNA-damaging compounds that sometimes arise in cells. In fact, mitochondria themselves give rise to many DNA-damaging oxygen compounds as byproducts of their own energy-making process especially in more complex animals that move around and burn lots of energy doing so. Thus, animal mitochondrial DNA has a faster mutation rate than animal cell-nucleus DNA.
Damage to mitochondrial genes also can't be managed as easily as in cell-nucleus genes. In sexually reproducing organisms, mitochondria and the DNA they contain originate always from the mother's egg cell. There is no recombination with paternal DNA to remove defects, as occurs for the main part of the genome. Since mutations that occur randomly are much more likely to be harmful than helpful, genomes that are passed along in this manner could simply accumulate defects, from one generation to the next, until they become totally dysfunctional. Biologists still do not fully understand how mitochondria have avoided this fate.
In their study, Schimmel and colleagues, including co-corresponding author Bernhard Kuhle, PhD, a postdoctoral research associate in the Scripps Research Laboratories for tRNA Synthetase Research, addressed this question with an analysis of mitochondrial tRNAs. The 22 distinct mt-tRNAs account for most of the molecules encoded by the mitochondrial genome. Like non-mitochondrial tRNAs, these molecules work as essential decoders of the genetic code, linking nucleotide sequences copied out from genes to corresponding amino acids, which are the building blocks of proteins.
The scientists analyzed the evolution of modern animal mt-tRNAs by comparing the mt-tRNAs of simple and complex animals and other, more evolutionarily distant organisms, and by mutating human mt-tRNAs to see how this changed their functions.
They found evidence suggesting that when the first moderately complex animals appeared on Earth, their mt-tRNAs evolved smaller, simpler structures, which made them more likely to maintain their decoder functions even when they accumulated new mutations.
This adaptation for mutational freedom would have allowed the genes for mitochondrial tRNAs to mutate even faster, and although mt-tRNA-linked genetic diseases are not very common in humans in an absolute sense, mt-tRNA genes are considered a relative hotspot for genetic disease. From this perspective, tRNA-associated mitochondrial diseases are a necessary price we pay for the high adaptive power of these important molecules, Schimmel says.
Authors of Relaxed sequence constraints favor mutational freedom in idiosyncratic metazoan mitochondrial tRNAs are Bernhard Kuhle and Paul Schimmel of Scripps Research, and Joseph Chihade of Carleton College.
Support was provided by the National Institutes of Health (R01 GM125908, R15 GM071392), the National Foundation for Cancer Research and the Skaggs Foundation.
Chemistry Schimmel, Paul
LINK: | https://www.scripps.edu/news-and-events/press-room/2020/20200228-schim... |
See more stories from scripps |
More from Scripps
13/03/2024
March 13, 2024
New computational strategy boosts the ability of drug designers to target proteins inside the membrane Customized-design approach could streamline the design of...
29/02/2024
February 29, 2024
Scripps Research scientists reveal how first cells could have formed on Earth New phospholipid discovery brings researchers closer to understanding how primordi...
29/02/2024
February 28, 2024
How molecular handedness emerged in early biology Scripps Research chemists fill a major gap in origin-of-life theories. February 28, 2024 LA JOLLA, CA Mole...
22/02/2024
February 21, 2024
Snaking toward a universal antivenom Scripps Research scientists discovered antibodies that protect against a host of lethal snake venoms. February 21, 2024 ...
06/02/2024
February 06, 2024
Calibr-Skaggs announces expansion of option and license agreement with AbbVie to develop novel cell therapies for solid tumors and autoimmune diseases AbbVie...
26/01/2024
January 25, 2024
Re-energizing mitochondria to treat Alzheimer's disease Scripps Research team restored neuron-to-neuron connections in human cells. January 25, 2024 LA JO...
24/01/2024
January 04, 2024
100 years of Science Changing Life: Scripps Research celebrates a century of transforming human health For the last century, institute leaders and renowned scie...
23/01/2024
January 23, 2024
New technology lets researchers track brain cells' off switches The method could shed light on what goes awry in numerous brain conditions when neurons ar...
09/01/2024
January 08, 2024
Three decades of giving: Announcing the Calibr-Skaggs Institute for Innovative Medicines The ALSAM Foundation, founded by the Skaggs family, provides lasting g...
04/01/2024
January 03, 2024
Life science entrepreneur Gene Lay joins Scripps Research Board of Directors Lay, founder of the global biotech company BioLegend, brings invaluable experience ...
21/12/2023
December 20, 2023
Taming a plant-derived toxin Scripps Research team modifies the traditional poison picrotoxinin for potential neurological drugs and anti-parasite treatments. ...
19/12/2023
December 18, 2023
Scripps Research Executive Vice President Eric Topol gives TED talk on transformative power of AI in medicine Topol provides an overview of how AI models can i...
13/12/2023
December 12, 2023
New AI-powered algorithm could better assess people's risk of common heart condition Early detection of atrial fibrillation can reduce the risk of stroke an...
07/12/2023
December 06, 2023
Nanoparticle flu vaccine design shows promise in early tests Scripps Research-designed vaccine could provide broad, enduring protection against influenza A str...
16/11/2023
November 15, 2023
Numerous Scripps Research scientists named Highly Cited Researchers Clarivate's annual, global list represents researchers who have demonstrated significant...
07/11/2023
November 06, 2023
Multiple sclerosis drug invented at Scripps Research slows long-term devastating disease progression Late-breaking data reinforces the effectiveness and safety ...
05/10/2023
October 04, 2023
Keren Lasker named a 2023 Moore Inventor Fellow The prestigious award will support Lasker's inventive research in membraneless organelles and their applica...
22/09/2023
September 21, 2023
Michael Bollong named a 2023 Amgen Young Investigator The prestigious award will support Bollong's research identifying new molecular targets and therapeuti...
09/09/2023
September 08, 2023
Philip Dawson receives 2024 American Chemical Society National Award Dawson is honored with the Arthur C. Cope Late Careers Scholar Award for his foundational c...
07/09/2023
September 06, 2023
Scripps Research chemists devise a method for C-H activation of alcohols The method represents a new toolkit for making drugs and other compounds. September 06...
31/08/2023
August 30, 2023
Scripps Research receives $1.5M to surveil infectious disease threats in wastewater Bill & Melinda Gates Foundation award to support the development of multi-pa...
16/08/2023
August 16, 2023
How cold temperatures trigger the brain to boost appetite Scripps Research scientists' discovery could lead to new weight loss and metabolic health treatmen...
08/08/2023
August 07, 2023
Human antibody that targets carfentanil, fentanyl and related opioids reverses overdose effects in preclinical study Scripps Research-developed antibody therapy...
04/08/2023
August 03, 2023
How sensory neurons impact the gut Scripps Research scientists show that the receptor PIEZO2 in sensory neurons controls gut motility and transit time, which a...
26/07/2023
July 26, 2023
AbbVie and Calibr Expand Strategic Collaboration to Advance Several Preclinical and Early-stage Clinical Assets The expanded strategic collaboration will advan...
23/07/2023
July 21, 2023
Scripps Research scientists develop AI-based tracking and early-warning system for viral pandemics Machine-learning system effectively predicts emergence of pro...
19/07/2023
July 19, 2023
Monitoring T cells may allow prevention of type 1 diabetes Scripps Research study shows that analyzing T cells in blood samples could be used to select at-risk ...
19/07/2023
July 18, 2023
Scripps Research mourns passing of leading organic chemist Albert Eschenmoser Eschenmoser pioneered key reactions in synthetic chemistry and shaped the understa...
15/06/2023
June 14, 2023
Scripps Research awarded $46.8 million by NIH to promote human health through innovative translational science and training The Translational Institute is harne...
13/06/2023
June 13, 2023
Scripps Research's Danielle Grotjahn named 2023 Pew Scholar in the Biomedical Sciences The award will support Grotjahn's study of how cells assemble the...
31/05/2023
May 31, 2023
Crossing the ring: new method enables C-H activation across saturated carbocycles Scripps Research chemists add another powerful tool to their molecular editin...
24/05/2023
May 23, 2023
Scripps Research develops behind-the-scenes tool for better biomedical data discovery The new resource makes datasets more discoverable for life science communi...
19/05/2023
May 15, 2023
Scripps Research neuroscientist Hollis Cline elected to American Academy of Arts and Sciences Cline is recognized for her discoveries about the role of sensory ...
19/05/2023
May 18, 2023
Scripps Research's Skaggs Graduate School awards doctoral degrees to 31st graduating class Commencement ceremony will be livestreamed via Zoom and on instit...
13/05/2023
May 12, 2023
A better route to benzocyclobutenes, sought-after building blocks for drugs Scripps Research chemists devise a new, C-H activation-based method for the synthesi...
09/05/2023
May 08, 2023
Renowned Scripps Research professor Jeffery Kelly elected to National Academy of Sciences Kelly's groundbreaking work on protein misfolding has led to thera...
28/04/2023
April 27, 2023
Mirror-image molecules pave new path for cancer drug discovery By comparing how mirror image versions of small molecules impact clusters of proteins, Scripps R...
22/04/2023
April 21, 2023
How alcohol consumption contributes to chronic pain A Scripps Research team showed how both alcohol intake and alcohol withdrawal can lead to increased pain and...
21/04/2023
April 20, 2023
Xin Jin receives dual awards to study autism risk genes in neurodevelopment Major grants from the National Institutes of Health and California Institute for Reg...
20/04/2023
April 19, 2023
Trim the sugar: New HIV vaccine design improves immune response Scripps Research vaccine candidate headed for clinical trials. April 19, 2023 LA JOLLA, CA A...
18/04/2023
April 17, 2023
Therapeutic can seek and destroy potent opioid to treat overdoses Scripps Research chemists developed a new biologic to work against the synthetic opioid carfen...
07/03/2023
March 06, 2023
How heavy alcohol consumption increases brain inflammation The findings by a Scripps Research team point toward a potential new drug target for treating alcohol...
02/03/2023
March 01, 2023
Scientists find human antibodies that can block multiple coronaviruses including SARS-CoV-2 Results from a Scripps Research and UNC team pave the way for a vacc...
28/02/2023
February 28, 2023
$10 million grant funds Scripps Research Alcohol Research Center through its 50th year The five-year grant supports research into the neurobiology of alcohol us...
28/02/2023
February 27, 2023
Immune system drug shows promise in treating alcohol use disorder, a Scripps Research clinical trial reports Scientists at Scripps Research found that apremilas...
23/02/2023
February 16, 2023
Chemically poisoned protein acts as a molecular switch to spur cancer formation The discovery triggered development of a new potential drug to eliminate tumor...
23/02/2023
February 23, 2023
Two new papers demonstrate use of Outbreak.info as one-stop online source for COVID data Scripps Research scientists highlight the need for continued monitorin...
15/02/2023
February 15, 2023
Calibr and Bill & Melinda Gates Medical Research Institute announce licensing agreement for novel candidate tuberculosis treatment compound Calibr transitions i...
08/02/2023
February 07, 2023
Scripps Research Professor Jeffery Kelly awarded 2023 Wolf Prize in Chemistry Kelly receives the prestigious award for his seminal discoveries in protein-foldin...
31/01/2023
January 30, 2023
Experimental anti-depression drug may also be useful in treating alcohol use disorder Investigational, clinical-stage antidepressant MAP4343 shown to reduce alc...