Publisher Health

DNA analysis of thousands of tumours from NHS patients has found a ‘treasure trove’ of clues about the causes of cancer, with genetic mutations providing a personal history of the damage and repair processes each patient has been through.
In the biggest study of its kind, a team of scientists led by Professor Serena Nik-Zainal from Cambridge University Hospitals (CUH) and University of Cambridge, analysed the complete genetic make-up or whole-genome sequences of more than 12,000 NHS cancer patients.
Because of the vast amount of data provided by whole genome sequencing, the researchers were able to detect patterns in the DNA of cancer — or ‘mutational signatures’ — that provide clues about whether a patient has had a past exposure to environmental causes of cancer such as smoking or UV light, or has internal, cellular malfunctions.
The team were also able to spot 58 new mutational signatures, suggesting that there are additional causes of cancer that we don’t yet fully understand.
This research was supported by Cancer Research UK and published today in the journal Science. The genomic data were provided by the 100,000 Genomes Project an England-wide clinical research initiative to sequence 100,000 whole genomes from around 85,000 patients affected by rare disease or cancer.
Dr Andrea Degasperi, research associate at the University of Cambridge and first author said: “Whole genome sequencing gives us a total picture of all the mutations that have contributed to each person’s cancer. With thousands of mutations per cancer, we have unprecedented power to look for commonalities and differences across NHS patients, and in doing so we uncovered 58 new mutational signatures and broadened our knowledge of cancer.”
Serena Nik-Zainal, a professor of genomic medicine and bioinformatics at the University of Cambridge and an honorary consultant in clinical genetics at CUH said: “The reason it is important to identify mutational signatures is because they are like fingerprints at a crime scene — they help to pinpoint cancer culprits. Some mutational signatures have clinical or treatment implications — they can highlight abnormalities that may be targeted with specific drugs or may indicate a potential ‘Achilles heel’ in individual cancers.
“We were able to perform a forensic analysis of over 12,000 NHS cancer genomes thanks to the generous contribution of samples from patients and clinicians throughout England. We have also created FitMS, a computer-based tool to help scientists and clinicians identify old and new mutational signatures in cancer patients, to potentially inform cancer management more effectively.”
Michelle Mitchell, chief executive of Cancer Research UK, said: “This study shows how powerful whole genome sequencing tests can be in giving clues into how the cancer may have developed, how it will behave and what treatment options would work best. It is fantastic that insight gained through the NHS 100,000 Genomes Project can potentially be used within the NHS to improve the treatment and care for people with cancer.”
Professor Matt Brown, chief scientific officer of Genomics England said: “Mutational signatures are an example of using the full potential of WGS. We hope to use the mutational clues seen in this study and apply them back into our patient population, with the ultimate aim of improving diagnosis and management of cancer patients.”
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New research from the University of Sheffield has revealed how fungus blocks and bursts blood vessels in the brain, helping scientists better understand how meningitis starts.
The study, published in the journal PLoS Pathogens, shows that Cryptococcus neoformans microbes become lodged in blood vessels preventing blood flow and increasing blood pressure. These microbes grow in the small blood vessels causing them to stretch and burst, releasing the infectious microbes into the brain and causing meningitis.
Meningitis is most commonly caused by an infection of the brain and spinal cord and can be life threatening if not recognised and treated very quickly. It is most common in babies, adolescents and those with compromised immune systems and affects an estimated 2.5 million people each year.
Dr Simon Johnston, from the University of Sheffield’s Department of Infection, Immunity and Cardiovascular Disease, said: “The brain has very complex and effective defences against microbes, but we have identified a simple and effective method that microbes may use to escape the blood and enter the brain.
“Previous research has focused on how microbes can break down the defences of the brain or use immune cells as a route into the brain. We can demonstrate how, for some microbes, damaging blood vessels is a very effective method of invasion.
“Our immune system is very effective at recognising and destroying microbes, including in the blood. However, some microbes can escape the immune cells and it is these microbes that would be most effective at using blood vessels bursting as a way into the brain.”
The research was carried out in collaboration with the Agency of Science, Technology and Research (A-Star), Singapore, and the University of Queensland, Australia.
The international research team, led by Dr Johnston, investigated zebrafish larvae to understand how the meningitis infection behaves in blood vessels. The findings will also help researchers better understand other blood vessel related diseases such as cardiovascular and neurological diseases.
Dr Johnston added: “We started this research because we knew there was unexplained blood vessel damage in some meningitis patients. We are now working to find new treatments for these patients.
“The infections causing meningitis can be treated with antimicrobials but patients are often very ill and a lot of damage can be caused before treatment is effective. This will be made worse by the ongoing global increase in antimicrobial resistant infections.
“We are using the knowledge we have gained from studying how meningitis can spread to understand how to reduce the damage caused to the brain while treatment takes place.”
The research was funded by the Medical Research Council, A-STAR Institute of Molecular and Cell Biology and Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology.
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Displaying the highway death toll on message boards is a common awareness campaign, but new research from the University of Toronto and University of Minnesota shows this tactic actually leads to more crashes.
A new study in Science by University of Toronto Assistant Professor Jonathan D. Hall and U of M Carlson School of Management Assistant Professor Joshua Madsen evaluated the effect of displaying crash death totals on highway message boards (e.g., “1669 deaths this year on Texas roads”). Versions of highway fatality messages have been displayed in at least 27 US states.
Their study focuses on Texas, where officials chose to display these messages only one week each month. The researchers compared crash data from before the campaign (Jan. 2010 — July 2012) to after it started (Aug. 2012 — Dec. 2017) as well as examined the weekly differences within each month during the campaign. They found: There were more crashes during the week with fatality messaging compared to weeks without. Displaying a fatality message increased the number of crashes over the 10 km (6.21 mi) following the message boards by 4.5%. This increase is comparable to raising the speed limit 3-5 mph or reducing highway troopers by 6-14%, according to previous research. Their findings suggest fatality messages cause an additional 2,600 crashes and 16 deaths per year in Texas, costing $377 million each year. The researchers suggest this “in-your-face” messaging approach weighs down drivers’ “cognitive loads,” temporarily impacting their ability to respond to changes in traffic conditions.”Driving on a busy highway [and] having to navigate lane changes is more cognitively demanding than driving down a straight stretch of empty highway,” said Madsen. “People have limited attention. When a driver’s cognitive load is already maxed out, adding on an attention-grabbing, sobering reminder of highway deaths [can] become a dangerous distraction.”
The researchers found the bigger the number in the fatality message, the more harmful the effects. The number of additional crashes each month increased as the death toll rose throughout the year, with the most additional crashes occurring in January when the message stated the annual total. They also found that crashes increased in areas where drivers experienced higher cognitive loads, such as heavy traffic or driving past multiple message boards.
“The messages also increased the number of multi-vehicle crashes, but not single-vehicle crashes,” said Hall. “This is in line with drivers with increased cognitive loads making smaller errors due to distraction, like drifting out of a lane, rather than driving off the road.”
However, the researchers found there was a reduction in crashes when the displayed death tolls were low and when the message appeared where the highways were less complex. Madsen says this suggests that at times the messaging was not as taxing on drivers’ attention.
While the use of highway fatality messaging varies by state, Madsen says agencies should consider alternative ways to raise awareness.
“Distracted driving is dangerous driving,” said Madsen. “Perhaps these campaigns can be reimagined to reach drivers in a safer way, such as when they are stopped at an intersection, so that their attention while driving remains focused on the roads.”
This research was supported by the Social Sciences and Humanities Research Council of Canada and the European Union’s Horizon 2020 research and innovation programme.
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To get to the places where they are needed, immune cells not only squeeze through tiny pores. They even overcome wall-like barriers of tightly packed cells. Scientists at the Institute of Science and Technology Austria (ISTA) have now discovered that cell division is key to their success. Together with other recent studies, their findings published in Science magazine give the full picture of a process just as important for healing as for the spread of cancer.
Imagine a stone wall in the countryside. Tightly packed, one stone sits on top of the other filling the tiniest gaps. A seemingly unbreachable obstacle. On their way throughout the body to fight infections, immune cells face such barriers in the form of cell-dense tissues. To do their job as the body’s rescue service, they need to find a way through. In a recent study, scientists from ISTA’s Siekhaus group together with collaborators from the European Molecular Biology Laboratory (EMBL) and three students from a local High School, took a close look at how this happens in fruit fly embryos.
During the development of these tiny, transparent animals, macrophages, the dominant form of immune cells in fruit flies, infiltrate tissues. Using high-end microscopes, the scientists were able to follow their journey. “The macrophages arrive at the wall and look for the right place to enter,” explains Maria Akhmanova, until recently a postdoc at Daria Siekhaus’ research group and first author of the study.
Breaking new ground
Cues that guide the macrophages have directed them to the right spot. There, the pioneer macrophage, the first cell to move in, is waiting. Suddenly, a part of the wall starts to move. The cell right in front of the macrophage rounds up, preparing to divide — a normal part of its cell cycle. “This is what the pioneer has been waiting for,” says Akhmanova. Moving its cell nucleus ahead, the pioneer cell now pushes forward while all the other macrophages follow in its tracks. As the Siekhaus group also recently discovered, to break through the pioneer gets an extra boost of energy through a complex process governed by a newly discovered protein the scientists named Atossa. Furthermore, the scientists learned that to shield their sensitive nucleus from damage, the macrophages develop protective armor made from actin filaments.
Cell division crucial for success
By precisely inhibiting, slowing down, and speeding up the division specifically of the flanking tissue cells, the researchers were now able to prove that the crucial component that allows immune cells to enter is in fact surrounding cell division. As it rounds up to prepare for division, the tissue cell at the entry site loses some of its connection points to its surroundings, the researchers observed through live imaging. In collaboration with the De Renzis lab at EMBL, the researchers also artificially induced rounding through a cutting edge technique using light to induce genetic changes. This wasn’t sufficient to get the macrophages to enter. But genetically reducing the amount of the cell connections was. “It was very exciting to see how the macrophages were only able to enter the tissue when the tissue cell lost its connections,” says Akhmanova.
Powerful implications for cancer research
“Cell division being the key process that controls macrophage infiltration is really a very elegant concept with powerful implications,” Professor Daria Siekhaus enthuses. The same mechanism that helps macrophages enter tissues could also be essential for many other types of immune cells in vertebrates like humans. In the long run, the scientists are eager to learn if manipulating the connections or the divisions of the tissue cells could help increase immune cells’ infiltration of tumors to fight them from within or help reduce immune cells’ ability to attack tissues during autoimmunity. “Our findings will also affect any researcher who is working on any migrating cell in the context of the body,” the cell biologist explains.
For her study, the theoretical biophysicist and Lise Meitner fellow Maria Akhmanova delved deep into the world of microscopy. With the help of her mentor Daria Siekhaus, she learned everything she could about the fascinating and very helpful fruit flies. Three students from the Klosterneuburg High School were also part of the team. During a school trip to the Institute’s laboratories, they discovered their enthusiasm for research. Consequently they helped Akhmanova with crossing and identifying fruit flies and even wrote an algorithm to speed up image analysis. “The success of this research project was made possible by joint forces from many scientists and enormous help from three motivated high school students!” says Akhmanova.
The ISTA project part was supported by funding from the Austrian Science Fund FWF: Lise Meitner Fellowship.
Video: https://youtu.be/IdVBkLXYfXg

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesHealth officials are now investigating 108 cases of sudden-onset hepatitis – or liver inflammation – in children in the UK since the start of this year.They say it is increasingly likely a virus which causes flu symptoms, known as adenovirus, could be the cause.Officials are examining 79 confirmed cases in England, 14 in Scotland and 15 across Wales and Northern Ireland.The UK Health Security Agency (UKHSA) said eight children had received a liver transplant as a result.Childhood hepatitis: Why are we seeing an unusual spike in cases?Cases of hepatitis in young children investigated The first sign of an unusual rise in young children with liver inflammation was spotted in Scotland in late March.Most of the children hospitalised so far are thought to be between the ages of one and five years old. Common virusUKHSA’s chief medical advisor, Professor Susan Hopkins, says that officials were still looking at a range of possible factors that could be behind the increase, but “the most likely” trigger was an adenovirus – a group of common viruses which usually cause colds, vomiting and diarrhoea in children.”Transplants in this age group are extremely rare so therefore we are concerned, and we want to understand why this is happening and what else we can do,” she told the BBC.Prof Hopkins says 77% of childhood hepatitis cases currently under investigation have tested positive for some form of adenovirus. Scientists and clinicians are now investigating whether there has been a change in the genetic make-up – or genome – of the virus that might trigger liver inflammation more easily.Another possible explanation is that restrictions imposed in the pandemic may have led to young children being first exposed to adenovirus at a slightly later point in their lives, leading to a “more vigorous” immune response.The UKHSA says it is keeping an “open mind” and not ruling out other possible causes, including Covid-19, other infections or an environmental trigger.But it says there is “no link” with the Covid-19 vaccine, as none of the children involved has been vaccinated.Good handwashingTo minimise the chance of an infection, Prof Hopkins says parents should supervise good handwashing and hygiene at home. “The good things that we’ve learnt from reducing transmission of Covid will help us reduce the transmission of whatever is causing this as well,” she says.The UKHSA has told parents and guardians to be on the lookout for the signs of hepatitis such as jaundice – a yellowing of the eyes and skin – and contact a GP if they are concerned.Other symptoms of the liver condition include:dark urineitchy skin muscle pain loss of appetiteEarlier this week, the European Centre for Disease Control said an undisclosed number of childhood hepatitis cases had also been detected in Denmark, Ireland, the Netherlands and Spain. In the US, Alabama’s public-health department said nine cases had been found in one- to six-year-olds, with two needing liver transplants.What is hepatitis?It’s a broad term used to describe inflammation of the liver.Usually the result of a viral infection, it can also be caused by exposure to some chemicals, drinking too much alcohol, drugs and certain genetic disorders.There are five main types of hepatitis caused by specific viruses – known as A, B, C, D and E – but none of those so far appears to have caused the liver inflammation seen in these children.Some types of hepatitis can pass without any serious problems, while others can be long-lasting.Source: Hepatitis – NHSMore on this storyRise in childhood hepatitis – what we know so farCases of hepatitis in young children investigated

Propelling micrometre-sized drones using light only and exerting precise control: Physicists at the University of Würzburg have succeeded at this for the first time. Their microdrones are significantly smaller than red blood cells.
A hand-held laser pointer produces no noticeable recoil forces when it is “fired” — even though it emits a directed stream of light particles. The reason for this is its very large mass compared to the very small recoil impulses that the light particles cause when leaving the laser pointer.
However, it has long been clear that optical recoil forces can indeed have a very large effect on correspondingly small particles. For example, the tails of comets point away from the Sun partly due to light pressure. The propulsion of light spacecrafts via light sails has also been discussed repeatedly, most recently in connection with the “star shot” project, in which a fleet of miniature spacecrafts is to be sent to Alpha Centauri.
Ordinary quadcopter drones as models
In the journal Nature Nanotechnology, Würzburg physicists led by Professor Bert Hecht (Chair of Experimental Physics 5, Nano-Optics Group) have now shown for the first time that it is possible to not only efficiently propel micrometre-sized objects in an aqueous environment with light, but also control them precisely on a surface with all three degrees of freedom (two translational plus one rotational).
In doing so, they were inspired by ordinary quadcopter drones, where four independent rotors allow complete control of the movements. Such control possibilities offer completely new options for the usually extremely difficult handling of nano- and micro-objects, for example, for the assembly of nanostructures, for the analysis of surfaces with nanometre precision, or in the field of reproductive medicine.

Do a person’s antibodies work to block the COVID-19 virus from infecting one’s system? Are these antibodies also capable of blocking emerging variants such as the omicrons?
These are the questions everyone is asking. And researchers at George Mason University have developed, Ha-CoV-2, a non-replicating rapid SARS-CoV-2 pesudovirus system that can quickly and quantitatively measure the ability of one’s antibodies to block SARS-CoV-2 and its variants in vitro.
A cross-disciplinary team coordinated by scientists at Mason’s Center for Infectious Disease Research (CIDR) has developed the hybrid alphavirus-SARS-CoV-2 pseudovirus system that can robustly express reporter genes in cells within hours to rapidly measure neutralizing antibodies. Ha-CoV-2 pseudovirus was utilized against the COVID-19 virus and its variants including Alpha, Delta, and Omicron, as well as the currently emerging omicron BA.2 variant.
This cutting-edge technology, recently published in the journal Cell Reports Methods, reduces a typical two-day process down to a few hours. The Mason team began working on this challenge when COVID-19 first emerged in the public eye and this important breakthrough was possible due to a combination of factors.
According to Dr. Yuntao Wu, a professor and virologist in Mason’s College of Science and team’s primary investigator, “The lab leveraged learnings from our prior HIV and polio virus research and Mason’s extensive, high-level and integrated infectious disease facilities, just as the SARS CoV-2 virus emerged.”
Brian Hetrick, who performed novel viral vector-based research with Wu, co-invented the pseudo virus system while pursuing his PhD at Mason. “I attempted to make a hybrid alphavirus vector-based pseudovirus for SARS-CoV-2. We hoped to have a more robust and rapid system for screening and measuring antiviral drugs and antibodies. We luckily got it after a few failed attempts,” Hetrick said.

New research shows that a treatment for retinal vein occlusion yields long-lasting vision gains, with visual acuity remaining significantly above baseline at five years. However, many patients require ongoing treatment. Retinal vein occlusion is one of the most common blinding conditions in the United States; without treatment, central retinal vein occlusion (CRVO), the most severe type of retinal vein occlusion often leads to significant and permanent vision loss. A report on five-year outcomes of the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2), was published April 21 in American Journal of Ophthalmology. SCORE2 was funded in part by the National Eye Institute (NEI), a part of the National Institutes of Health.
Retinal vein occlusion is caused by a blockage of the veins carrying blood away from the retina, the light-sensitive tissue at the back of the eye. This blockage can lead to macular edema where fluid becomes trapped within and under the retina, leading to rapid and severe loss of visual acuity. Without treatment, this condition typically leads to permanent loss of vision. The most effective treatment, injections of anti-vascular endothelial growth factor (VEGF) drugs, helps control blood vessel leakage and swelling in the retina.
“While anti-VEGF therapy is associated with significant improvement in both retinal swelling and visual acuity in patients with central or hemi-retinal vein occlusion, our findings show that most of the patients followed still required treatment to control the macular edema for at least five years,” said Ingrid U. Scott, M.D., M.P.H., Penn State College of Medicine, Hershey, chair of the study. “This demonstrates the importance of continued monitoring of these patients.”
In 2017, SCORE2 clinical trial investigators reported that two types of anti-VEGF treatment were equally effective at improving visual acuity in people with macular edema due to CRVO or hemi-retinal vein occlusion (HRVO). CRVO affects the entire retina, while HRVO generally affects about half of the retina. Half of the study participants had been given Avastin (bevacizumab) while the other half received Eylea (aflibercept). Both drugs were administered by injection once per month for six months. At the six-month mark, the vision of participants in both groups had, on average, improved over three lines on an eye chart.
As detailed in this new report, the study investigators followed SCORE2 participants for five years, collecting information about their visual acuity, treatments, and whether their macular edema had resolved. After the initial 12-month study period, participants were treated at their physician’s discretion. Most physicians reduced the frequency of anti-VEGF injections and some switched their patients to the other anti-VEGF drug. At five years, many participants had lost some visual acuity when compared to their acuity at the 12-month mark; however, they retained on average three lines of improvement, compared to their acuity at the beginning of the study.
“It was surprising to us that despite many participants still needing treatment after five years, their visual acuity outcome remained very good,” said Michael Ip, M.D., co-chair of the study from Doheny Eye Institute, University of California Los Angeles. “In comparison to this treatment for wet age-related macular degeneration, where initial vision improvements fade over time, these results are quite favorable.”
“This five-year study tells us a lot about what’s happening with retinal vein occlusion patients in the real world,” said Scott. “Prior to this study, retinal vein occlusion was widely considered an acute illness. This study shows that RVO is a chronic disease. It also underscores the importance of disease monitoring and individualized treatment to achieve the best possible vision.”
“The SCORE2 study provides invaluable data to guide clinicians and their patients toward informed decisions regarding treatment for retinal vein occlusion,” said NEI Director Michael F. Chiang, M.D.
The SCORE2 study was funded by NEI and Research to Prevent Blindness. Study drugs were provided by Regeneron, Inc and Allergan, Inc. Clinical trial number: NCT01969708.
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Dentures may have a potentially negative impact on a person’s overall nutrition, according to new research from Regenstrief Institute and Indiana University School of Dentistry. The research team leveraged electronic dental and health records to gain a better understanding of how oral health treatments affect individuals’ overall health over time.
This is believed to be the first study to report the results of utilizing lab values of nutritional biomarkers and linking them with dental records.
“Dentures are a significant change for a person. They do not provide the same chewing efficiency, which may alter eating habits,” said senior author Thankam Thyvalikakath, DMD, MDS, PhD, director of the Regenstrief and IU School of Dentistry Dental Informatics program. “Dentists need to be aware of this and provide advice or a referral for nutrition counseling. These patients need support during the transition and possible continued monitoring.”
For the study, the research team matched the dental records of more than 10,000 patients in Indiana with medical laboratory data, specifically markers for malnutrition. The laboratory tests included complete blood count, basic metabolic profile and lipid and thyroid panel tests, among others. They compared the lab results from two years before a patient received dentures to the two years after.
Researchers found that people with dentures had a significant decline in certain nutrition markers over those two years. People who did not wear dentures did not experience this decline. The marker levels were still within normal range, but researchers say there is the potential that the levels will continue to fall as more time passes. They urge dentists to be aware of this possibility.
The next steps in this research area are to look at other factors that may influence nutrition, including insurance status and dental clinic characteristics.
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The process of “translation” in protein synthesis involves formation of a peptide bond between two amino acids that are attached to two distinct transfer RNAs (tRNAs). For long, scientists have been puzzled as to how these tRNAs evolutionarily lie so close to each other on the ribosome. In a new study, researchers explain how tRNA-like components act as scaffolds for peptide bond formation between amino acid-bound “RNA minihelices,” which are half tRNA-like molecules.
The genetic information stored in DNA is “decoded” to form proteins via the process of translation. This involves the formation of peptide bonds between amino acids bound to transfer RNA (tRNA) molecules that glide over the ribosome in very close proximity to each other, and elongate the peptide chain, which later undergoes conformational change, forming a protein. In contrast to the codon-dependent aminoacyl-tRNA recognition in the small ribosomal subunit, the peptide bond formation in question occurs at the peptidyl transferase center (PTC) of the large ribosomal subunit, in a non-amino acid specific manner. This non-specificity indicates that the large subunit evolved before the small subunit, which has more specific interactions with mRNA and tRNA.
Although the evolutionary process of PTC formation has been thoroughly documented, little is known about how ribosomes developed into functioning entities and became an essential component of protein synthesis. Scientists have long been perplexed by the fact that tRNAs require the help of a “scaffold” in order to create a peptide bond, which orients them for interaction via 3′-CCA sequences on their acceptor arms. What that scaffold is, and how it operates, would be intriguing to learn about.
A team of scientists at Tokyo University of Science, led by Prof. Koji Tamura, decided to solve this mystery using a perspective of continuity in biological evolution. Their study, which was published online on 12 April 2022 in Volume 12, Issue 4 of the journal Life, sheds light on the evolutionary aspect of protein translation. Their results represent important evidence to demonstrate the hypothesis about the origin and evolution of the PTC, which has changed the way we look at the modern-day ribosomes and tRNA.
The idea sprang to life after taking a close look at the crystal structure of the 70S ribosome-tRNA complex from Thermus thermophilus, a bacterium often used in the study of genetics. The peptidyl (P-) and aminoacyl (A-) sites of the tRNAs here aligned to bring the CCA termini in close proximity, like a rugby player’s index fingers in the “Goromaru pose.” “There was a certain entity that served as a scaffold for maintaining this proximity, and it most likely stemmed from the primordial PTC,” says Prof. Tamura. Since an evolutionary aspect was likely, the team chose to utilize primordial tRNA or “RNA minihelix” for their study.
They first attempted a peptide bond formation between two alanine-specific minihelices in the presence of a ribosomal RNA segment. The peptide bond was formed using the ribosomal segment, P1c2, as an RNA scaffold which was just 70 nucleotides long! Next, they added a terminal amino acid segment (with the sequence UGGU) to the P1c2 (P1c2UGGU). According to mass spectrometry results, this increased the peptide bond formation ability by 4.2 times that of the original! The peptide bond formation between two alanine residues was supported by a scaffold of dimerized P1c2UGGU. The UGGU sequence of the scaffold interacted with the corresponding 3′-terminal ACCA of the minihelix and brought the two amino acids near enough to create a peptide bond. Nobel laureate Dr. Ada Yonath and her group recently showed that similar, conserved PTC regions could catalyze peptide bond formation with artificial analog molecules, but Prof. Tamura’s group showed that an aminoacylated RNA could also be a substrate.
The findings definitely imply a possibility that minihelices bind to the primordial PTC. So, what do the results suggest about the evolution of ribosomes? “Functional interactions between the CCA of tRNA and PTC could have been ‘revised’ in the process of evolution. Although current ribosomes do not have a contiguous sequence like UGGU, their interactions are ‘conceptually’ similar to the effects seen in our study. It is plausible that minihelices eventually evolved into tRNA using, for example, kissing-loop interactions between two minihelix-like RNA molecules,” Prof. Tamura explains. “These minihelix-like molecules, which form a part of the scaffold for peptide bond formation, may have not only contributed to the evolution of what is currently the PTC, but also formed tRNA molecules,” he adds.
The future applications of this research — which has opened up exciting avenues in evolutionary RNA biology — are manifold. Faced with a metabolic paradox (that the components of DNA and RNA are generated from amino acids), it is conceivable to investigate the notion of “peptide nucleic acids” as genetic material precursors. The results are fascinating, and they will help scientists to decode molecular phenomena that have eluded them for years.
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