̽��ֱ�� of Cambridge - Genomics

Genetic study reveals hidden chapter in human evolution

sc604 — Tue, 18 Mar 2025 10:00:00 +0000

Using advanced analysis based on full genome sequences, researchers from the ̽��ֱ�� of Cambridge have found evidence that modern humans are the result of a genetic mixing event between two ancient populations that diverged around 1.5 million years ago. About 300,000 years ago, these groups came back together, with one group contributing 80% of the genetic makeup of modern humans and the other contributing 20%.

For the last two decades, the prevailing view in human evolutionary genetics has been that Homo sapiens first appeared in Africa around 200,000 to 300,000 years ago, and descended from a single lineage. However, these latest results, reported in the journal Nature Genetics, suggest a more complex story.

“ ̽��ֱ��question of where we come from is one that has fascinated humans for centuries,” said first author Dr Trevor Cousins from Cambridge’s Department of Genetics. “For a long time, it’s been assumed that we evolved from a single continuous ancestral lineage, but the exact details of our origins are uncertain.”

“Our research shows clear signs that our evolutionary origins are more complex, involving different groups that developed separately for more than a million years, then came back to form the modern human species,” said co-author Professor Richard Durbin, also from the Department of Genetics.

While earlier research has already shown that Neanderthals and Denisovans – two now-extinct human relatives – interbred with Homo sapiens around 50,000 years ago, this new research suggests that long before those interactions – around 300,000 years ago – a much more substantial genetic mixing took place. Unlike Neanderthal DNA, which makes up roughly 2% of the genome of non-African modern humans, this ancient mixing event contributed as much as 10 times that amount and is found in all modern humans.

̽��ֱ��team’s method relied on analysing modern human DNA, rather than extracting genetic material from ancient bones, and enabled them to infer the presence of ancestral populations that may have otherwise left no physical trace. ̽��ֱ��data used in the study is from the 1000 Genomes Project, a global initiative that sequenced DNA from populations across Africa, Asia, Europe, and the Americas.

̽��ֱ��team developed a computational algorithm called cobraa that models how ancient human populations split apart and later merged back together. They tested the algorithm using simulated data and applied it to real human genetic data from the 1000 Genomes Project.

While the researchers were able to identify these two ancestral populations, they also identified some striking changes that happened after the two populations initially broke apart.

“Immediately after the two ancestral populations split, we see a severe bottleneck in one of them—suggesting it shrank to a very small size before slowly growing over a period of one million years,” said co-author Professor Aylwyn Scally, also from the Department of Genetics. “This population would later contribute about 80% of the genetic material of modern humans, and also seems to have been the ancestral population from which Neanderthals and Denisovans diverged.”

̽��ֱ��study also found that genes inherited from the second population were often located away from regions of the genome linked to gene functions, suggesting that they may have been less compatible with the majority genetic background. This hints at a process known as purifying selection, where natural selection removes harmful mutations over time.

“However, some of the genes from the population which contributed a minority of our genetic material, particularly those related to brain function and neural processing, may have played a crucial role in human evolution,” said Cousins.

Beyond human ancestry, the researchers say their method could help to transform how scientists study the evolution of other species. In addition to their analysis of human evolutionary history, they applied the cobraa model to genetic data from bats, dolphins, chimpanzees, and gorillas, finding evidence of ancestral population structure in some but not all of these.

“What’s becoming clear is that the idea of species evolving in clean, distinct lineages is too simplistic,” said Cousins. “Interbreeding and genetic exchange have likely played a major role in the emergence of new species repeatedly across the animal kingdom.”

So who were our mysterious human ancestors? Fossil evidence suggests that species such as Homo erectus and Homo heidelbergensis lived both in Africa and other regions during this period, making them potential candidates for these ancestral populations, although more research (and perhaps more evidence) will be needed to identify which genetic ancestors corresponded to which fossil group.

Looking ahead, the team hopes to refine their model to account for more gradual genetic exchanges between populations, rather than sharp splits and reunions. They also plan to explore how their findings relate to other discoveries in anthropology, such as fossil evidence from Africa that suggests early humans may have been far more diverse than previously thought.

“ ̽��ֱ��fact that we can reconstruct events from hundreds of thousands or millions of years ago just by looking at DNA today is astonishing,” said Scally. “And it tells us that our history is far richer and more complex than we imagined.”

̽��ֱ��research was supported by Wellcome. Aylwyn Scally is a Fellow of Darwin College, Cambridge. Trevor Cousins is a member of Darwin College, Cambridge.

Reference:
Trevor Cousins, Aylwyn Scally & Richard Durbin. ‘A structured coalescent model reveals deep ancestral structure shared by all modern humans.’ Nature Genetics (2025). DOI: 10.1038/s41588-025-02117-1

Modern humans descended from not one, but at least 2 ancestral populations that drifted apart and later reconnected, long before modern humans spread across the globe.

Our history is far richer and more complex than we imagined

Aylwyn Scally

Jose A Bernat Bacete via Getty Images

Plaster reconstructions of the skulls of human ancestors

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Cutting-edge genomic test can improve care of children with cancer

Anonymous — Tue, 02 Jul 2024 09:00:37 +0000

̽��ֱ��study, published on 2 July in Nature Medicine, is the first time that the impact of using whole genome sequencing in current NHS practice has been assessed. It was led by researchers at the ̽��ֱ�� of Cambridge, Cambridge ̽��ֱ�� Hospitals NHS Trust, Wellcome Sanger Institute and Great Ormond Street Hospital.

̽��ֱ��team analysed the use of routine genome sequencing, through the NHS Genomic Medicine Service, at Cambridge ̽��ֱ�� Hospitals, where such tests are given to all children with solid tumours, and at Great Ormond Street Hospital, which provides the test for childhood leukaemia.

̽��ֱ��researchers found that cancer sequencing gave new insights that improved the immediate clinical care of seven per cent of children, while also providing all the benefits of current standard tests.

Furthermore, in 29 per cent of cases, genome sequencing provided additional information that helped clinicians better understand the tumours of individual children and informed future management. For example, uncovering unexpected mutations that increase future cancer risk leading to preventative measures being taken, such as regular screening.

Overall, whole genome sequencing provides additional, relevant data, about childhood cancer that is useful for informing practice. ̽��ֱ��results also show that it can reduce the number of tests required, and therefore, researchers suggest it should be provided to all children impacted by cancer.

Whole genome sequencing (WGS) is a single test that provides a complete readout of the entire genetic code of the tumour and identifies every single cancer-causing mutation. Comparatively, traditional standard-of-care tests only look at tiny regions of the cancer genome, and therefore many more tests are often required per child.

Professor Sam Behjati, senior author from the Wellcome Sanger Institute, Cambridge ̽��ֱ�� Hospitals, and the ̽��ֱ�� of Cambridge: “Whole genome sequencing provides the gold standard, most comprehensive and cutting edge view of cancer. What was once a research tool that the Sanger Institute started exploring over a decade ago, has now become a clinical test that I can offer to my patients. This is a powerful example of the genomic data revolution of healthcare that enables us to provide better, individualised care for children with cancer.”

NHS England is one of the few health services in the world that has a national initiative, through the Genomic Medicine Service, offering universal genome sequencing to every child with suspected cancer. However, due to multiple barriers and a lack of evidence from real-time practice supporting its use, whole cancer genome sequencing is not yet widespread practice.

̽��ֱ��latest study looked at 281 children with suspected cancer across the two units. ̽��ֱ��team analysed the clinical and diagnostic information across these units and assessed how genome sequencing affected the care of children with cancer.

They found that WGS changed the clinical management in seven per cent of cases, improving care for 20 children, by providing information that is not possible to acquire from standard of care tests.

Additionally, WGS faithfully reproduced every one of the 738 standard of care tests utilised in these 281 cases, suggesting that a single WGS test could replace the multiple tests that the NHS currently uses if this is shown to be economically viable.

WGS provides a detailed insight into rare cancers, for example, by revealing novel variants of cancer. ̽��ֱ��widespread use of genome sequencing will enable clinicians to access these insights for individual patients while simultaneously building a powerful shared genomic resource for research into new treatment targets, possible prevention strategies, and the origins of cancer.

Dr Jack Bartram, senior author from Great Ormond Street Hospital NHS Foundation Trust and the North Thames Genomic Medicine Service, said: “Childhood cancer treatment is mostly guided by genetic features of the tumour, and therefore an in-depth genetic understanding of cancer is crucial in guiding our practice. Our research shows that whole genome sequencing delivers tangible benefits above existing tests, providing better care for our patients. We hope this research really highlights why whole genome sequencing should be delivered as part of routine clinical care to all children with suspected cancer.”

Professor Behjati at the Department of Paediatrics, ̽��ֱ�� of Cambridge, and is a Fellow of Corpus Christi College, Cambridge.

This research was supported in part by Wellcome, the Pessoa de Araujo family and the National Institute for Health and Care Research.

Reference
A Hodder, S Leiter, J Kennedy, et al. Benefits for children with suspected cancer from routine whole genome sequencing. Nature Medicine; 2 July 2024; DOI: 10.1038/s41591-024-03056-w

Adapted from a press release from Wellcome Sanger Institute

Whole genome sequencing has improved clinical care of some children with cancer in England by informing individual patient care. Research published today supports the efforts to provide genome sequencing to all children with cancer and shows how it can improve the management of care in real-time, providing more benefits than all current tests combined.

This is a powerful example of the genomic data revolution of healthcare that enables us to provide better, individualised care for children with cancer

Sam Behjati

FatCamera (Getty Images)

Boy Battling With Cancer

Eddie’s story

When he was six-years old, Eddie began to have regular low-grade fevers that seemed to affect him a lot. Even though early tests came back normal, the fevers became more frequent and his Mum, Harri, noticed that on one or two occasions he seemed out of breath while doing small things like reading a book. A chest x-ray revealed a huge mass on Eddie’s chest, and he was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL). Eddie was immediately transferred to Great Ormond Street Hospital (GOSH) to begin treatment.

“I know it sounds like a cliché, but you really don’t think it will ever happen to your child. It felt like our world fell out from under us. During those first few weeks I remember wondering if this was it, I was taking so many photos of us together and wondering if it could be the last,” said Harri, Eddie's mum.

Eddie was put onto a treatment plan that included eight months of intense chemotherapy, followed by two and a half years of maintenance treatment. As part of his treatment at GOSH Eddie’s family were also offered WGS to identify any cancer-causing changes.

“When we were offered whole genome sequencing, we didn’t even hesitate. I wanted to have all the information, I wanted to have some peace of mind for the future and know that Eddie was having the right care throughout. I also wanted to make sure that Eddie’s brother, Leo, wasn’t any more likely to get T-ALL because Eddie had,” said Harri.

On his seventh birthday, Eddie’s family received the call to say he was in remission. Now, at nine years-old Eddie is nearing the end of his maintenance treatment and is doing well.

“We are trying to live each day, and this experience has really changed our outlook on life. We always try to take the positive from every situation. Words can’t explain what Eddie has been through this past three years but he has come out the other side as a sensitive, confident, and smart young man. He is mature beyond his years and he has been involved in everything, including decisions about his treatment. To say we are proud, doesn’t even come close to how we truly feel about him,” said Harri.

Their personal experience of WGS was so important on their journey that they provided support for this research.

Harri added: “I always say that having a child with a cancer diagnosis feels like you’ve been standing on a trap door all these years without knowing. Then after the diagnosis, you are in freefall. And even when things are stable again, you are constantly aware that the trap door is still there and there is a possibility it could open again at any time. Having access to whole genome sequencing gave us some sense of reassurance, it could have informed us about targeted treatments and gave us some insight into future risk. We wanted to support something that had the potential to have a real impact on treatment and outcomes so when we heard about this research project and its potential, it was very exciting that we could be a small part of it. It helped us turn something so devastating into something positive and we just hope that this research helps.”

Yes

Cambridge partners with AstraZeneca and Medical Research Council on new world-class functional genomics laboratory

skbf2 — Mon, 27 Nov 2023 10:30:22 +0000

̽��ֱ�� ̽��ֱ�� of Cambridge today announced a partnership with AstraZeneca and the Medical Research Council (MRC) to establish a new state-of-the-art functional genomics laboratory at the Milner Therapeutics Institute (MTI). ̽��ֱ��laboratory will become part of the UK’s Human Functional Genomics Initiative, contributing to the UK’s ambition of having the most advanced genomic healthcare system in the world.

Functional genomics investigates the effects and impacts of genetic changes in our DNA, and particularly how these contribute to disease. CRISPR makes it possible to test specific DNA alterations in a controlled way to investigate the effects and impacts of genetic changes in our DNA, revealing their effects on biological processes that cause disease. Finding these disease drivers is a key first step in the process of identifying potentially life-changing medicines for patients.

̽��ֱ��new facility, which will be located within the MTI on the Cambridge Biomedical Campus, will provide researchers from across the UK with access to large-scale biological and technological tools and house an advanced automated arrayed-CRISPR screening platform. It is hoped that through the use of tools, such as CRISPR gene editing to provide insights into the relationship between genes and disease, scientists will discover new opportunities to develop therapies for chronic diseases including cardiovascular, respiratory and metabolic disease.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute, said: “ ̽��ֱ��best science is founded on collaboration, and I am delighted that the Milner Therapeutics Institute is partnering with the MRC and AstraZeneca to launch this unique functional genomics laboratory. This will enable sharing of expertise and resources to deliver new diagnostics and treatments for people with chronic diseases.”

Professor Andy Neely, Pro-Vice-Chancellor for Enterprise and Business Relations at the ̽��ֱ�� of Cambridge, said: “This new collaboration with AstraZeneca and MRC is a fantastic example of industry and academia working together to drive forward science that will have a real impact on people’s health in the UK and around the world.”

Dr Jonathan Pearce, Director of Strategy and Planning, MRC, said: “We are working across UK Research and Innovation to improve health, ageing and wellbeing. Our investment in this new laboratory builds on the UK’s global leadership in genomics. Our support will enable the laboratory’s launch and provide access for researchers from across the UK. Through this investment, and the wider Human Functional Genomics Initiative, we will enhance the national ecosystem needed to improve our understanding of how genetic variance impacts health and disease.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Collaboration is crucial to achieving our ambition of transforming healthcare and delivering life-changing medicines for patients, and innovative partnership such as this one, allow us to share resources and expertise to advance science. This new laboratory created as part of the Human Functional Genomics Initiative, will be world-leading and will play a central role in shaping future functional genomics work across the UK and beyond.”

̽��ֱ��lab, which is expected to become operational in 2024, will provide a centre of excellence and national resource that combines the strengths and expertise of academia and industry. Its creation is part of a new partnership formed between MTI, AstraZeneca and MRC, and builds upon expertise gained through an existing collaboration between MTI, AstraZeneca and Cancer Research Horizons, known as the AstraZeneca-Cancer Research Horizons Functional Genomics Centre (FGC) that has been enabling advances in oncology research since 2018. ̽��ֱ��FGC is currently housed in the MTI and will be relocating next year.

MTI, AstraZeneca and the MRC’s Human Functional Genomics Initiative will share facilities, resources and knowledge working closely together to facilitate faster progress and innovations.

̽��ֱ��facility, based at the Milner Therapeutics Institute, will support the discovery of new medicines and diagnostics for chronic diseases by applying advanced biological and technological tools, including CRISPR gene editing.

A fantastic example of industry and academia working together to drive forward science that will have a real impact on people’s health in the UK and around the world.

Andy Neely

Milner Therapeutics Institute

Scientist looking down microscope

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

DNA discovery highlights how we maintain healthy blood sugar levels after meals

cjb250 — Thu, 08 Jun 2023 15:00:48 +0000

̽��ֱ��findings, published today in Nature Genetics, could help inform future treatments of type 2 diabetes, which affects around 4 million people in the UK and over 460 million people worldwide.

Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.

A key player in the development of the condition is insulin, a hormone that regulates blood sugar – glucose – levels. People who have type 2 diabetes are unable to correctly regulate their glucose levels, either because they don’t secrete enough insulin when glucose levels increase, for example after eating a meal, or because their cells are less sensitive to insulin, a phenomenon known as ‘insulin resistance’.

Most studies to date of insulin resistance have focused on the fasting state – that is, several hours after a meal – when insulin is largely acting on the liver. But we spend most of our time in the fed state, when insulin acts on our muscle and fat tissues.

It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ – a sugary drink, or a meal, for example – play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the ̽��ֱ�� of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.”

To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55,000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.

̽��ֱ��team identified new 10 loci – regions of the genome – associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.

One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.

To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.

Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. ̽��ֱ��less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.

Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”

Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.

Professor Claudia Langenberg, Director of the Precision Healthcare ̽��ֱ�� Research Institute (PHURI) at Queen Mary ̽��ֱ�� of London and Professor of Computational Medicine at the Berlin Institute of Health, Germany, said: “Our findings open up a potential new avenue for the development of treatments to stop the development of type 2 diabetes. It also shows how genetic studies of dynamic challenge tests can provide important insights that would otherwise remain hidden.”

̽��ֱ��research was supported by Wellcome, the Medical Research Council and the National Institute for Health and Care Research.

Reference
Williamson, A et al. Genome-wide association study and functional characterisation identifies candidate genes for insulin-stimulated glucose uptake. Nat Gen; 8 June 2023; DOI: 10.1038/s41588-023-01408-9

A study of the DNA of more than 55,000 people worldwide has shed light on how we maintain healthy blood sugar levels after we have eaten, with implications for our understanding of how the process goes wrong in type 2 diabetes.

What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work

Alice Williamson

eak_kkk (Pixabay)

Cola

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Licence type:

Public Domain

Evolution of two contagious cancers affecting Tasmanian devils underlines unpredictability of disease threat

cg605 — Thu, 20 Apr 2023 18:00:01 +0000

Transmissible cancers, which occur only rarely in the animal kingdom, are spread by the transfer of living cancer cells. In the case of Tasmanian devils, the cells are transferred through biting – a behaviour that is common in devils especially in fights over mates and food.

Tasmanian devils are susceptible to two fatal transmissible cancers called devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2) that have caused rapid population decline in recent decades. ̽��ֱ��two cancers both manifest with disfiguring facial tumours.

In a new study, ̽��ֱ�� of Cambridge researchers, together with a global team of scientists from Europe, Australia and the United States, mapped the emergence and mutations of DFT1 and DFT2 and characterised these cancers’ ongoing evolution. ̽��ֱ��findings underline the continued threat that transmissible cancers pose to Tasmanian devils.

̽��ֱ��results are published today in the journal Science.

“ ̽��ֱ��incredible fact that Tasmanian devils have not one, but two, transmissible cancers, makes it possible to compare their evolution, and this gives us new insights into the key mechanisms involved,” said lead author Elizabeth Murchison, Professor of Comparative Oncology and Genetics at the Department of Veterinary Medicine, ̽��ֱ�� of Cambridge.

“By looking at the mutations that have accumulated in these cancers’ DNA, we can trace the origins and evolution of these diseases. Our results show that the two cancers arose through similar processes and that both have striking signals of ongoing evolution. It is difficult to predict how this continued cancer evolution will impact devils.”

̽��ֱ��researchers created an improved ‘reference genome’ – essentially a map of the entire DNA sequence – of the Tasmanian devil and compared this to DNA taken from 119 DFT1 and DFT2 tumours. DFT1 was first observed in 1996 in Tasmania’s northeast and is now widespread throughout Tasmania. DFT2, on the other hand, was first observed in 2014 and remains confined to a small area in Tasmania’s southeast. ̽��ֱ��scientists identified mutations in the tumours and used these to build ‘family trees’ of how the two cancers had each independently arisen and evolved over time.

By tracking mutations the researchers discovered that DFT2 acquired mutations about three times faster than DFT1. As mutations usually occur during cell division, the most likely explanation is that DFT2 is a faster growing cancer than DFT1, say the researchers, underlining the importance of DFT2 as a threat.

“DFT2 is still not widespread in the devil population, and very little is known about it. We were really startled to see just how quickly it was mutating, alerting us to what could be a very unpredictable threat to the devils in the long term,” said Maximilian Stammnitz, first author of the study.

̽��ֱ��team found that DFT1 arose in the 1980s, up to 14 years before it was first observed, whereas DFT2 emerged between 2009 and 2012, only shortly before it was detected.

Mapping the mutations revealed that DFT1 underwent an explosive transmission event shortly after it emerged. This involved a single infected devil transmitting its tumour to at least six recipient devils.

DFT1 has now spread throughout almost the entire devil population and has recently been reported in the far northwest of Tasmania, one of the few remaining disease-free regions of the state.

Researchers also identified for the first time an instance of DFT1 transmission between a mother and the young in her pouch. Additionally, they found that the incubation period – the time between infection and the emergence of symptoms – can in some cases be a year or more. These findings have important implications for conservation scientists working to protect the species.

“I come from Tasmania and love Tasmanian devils – they have a special place in my heart,” said Murchison. “Transmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils. This research highlights the continuing importance of monitoring and conservation programmes. It also gives us new insights into the evolutionary mechanisms operating in cancer more broadly, including in human cancers.”

̽��ֱ��research was funded by Wellcome, the Gates Cambridge Trust and Eric Guiler Tasmanian Devil Research Grants from the ̽��ֱ�� of Tasmania Foundation.

Reference: M. R. Stammnitz et al. ̽��ֱ��evolution of two transmissible cancers in Tasmanian devils, Science, DOI: 10.1126/science.abq6453

Scientists have traced the family trees of two transmissible cancers that affect Tasmanian devils and have pinpointed mutations which may drive growth of deadly diseases.

Transmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils.

Professor Elizabeth Murchison

Max Stammnitz

Tasmanian Devil

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Should we allow genome editing of human embryos?

cjb250 — Tue, 28 Feb 2023 13:39:24 +0000

A citizens’ jury of individuals whose lives have been affected by hereditary disease has voted in favour of asking the UK government to consider changing the law to allow genome editing of human embryos to treat serious genetic conditions.

New route to evolution: how DNA from our mitochondria gets into our genomes

cjb250 — Wed, 05 Oct 2022 15:00:50 +0000

In a study published today in Nature, researchers at the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London show that mitochondrial DNA also appears in some cancer DNA, suggesting that it acts as a sticking plaster to try and repair damage to our genetic code.

Mitochondria are tiny ‘organelles’ that sit within our cells, where they act like batteries, providing energy in the form of the molecule ATP to power the cells. Each mitochondrion has its own DNA – mitochondrial DNA – that is distinct to the rest of the human genome, which is comprised of nuclear DNA.

Mitochondrial DNA is passed down the maternal line – that is, we inherit it from our mothers, not our fathers. However, a study published in PNAS in 2018 from researchers at the Cincinnati Children’s Hospital Medical Center in the USA reported evidence that suggested some mitochondrial DNA had been passed down the paternal line.

To investigate these claims, the Cambridge team looked at the DNA from over 11,000 families recruited to Genomics England’s 100,000 Genomes Project, searching for patterns that looked like paternal inheritance. ̽��ֱ��Cambridge team found mitochondrial DNA ‘inserts’ in the nuclear DNA of some children that were not present in that of their parents. This meant that the US team had probably reached the wrong conclusions: what they had observed were not paternally-inherited mitochondrial DNA, but rather these inserts.

Now, extending this work to over 66,000 people, the team showed that the new inserts are actually happening all the time, showing a new way our genome evolves.

Professor Patrick Chinnery, from the Medical Research Council Mitochondrial Biology Unit and Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge, explained: “Billions of years ago, a primitive animal cell took in a bacterium that became what we now call mitochondria. These supply energy to the cell to allow it to function normally, while removing oxygen, which is toxic at high levels. Over time, bits of these primitive mitochondria have passed into the cell nucleus, allowing their genomes to talk to each other.

“This was all thought to have happened a very long time ago, mostly before we had even formed as a species, but what we've discovered is that that’s not true. We can see this happening right now, with bits of our mitochondrial genetic code transferring into the nuclear genome in a measurable way.”

̽��ֱ��team estimate that mitochondrial DNA transfers to nuclear DNA in around one in every 4,000 births. If that individual has children of their own, they will pass these inserts on – the team found that most of us carry five of the new inserts, and one in seven of us (14%) carry very recent ones. Once in place, the inserts can occasionally lead to very rare diseases, including a rare genetic form of cancer.

It isn’t clear exactly how the mitochondrial DNA inserts itself – whether it does so directly or via an intermediary, such as RNA – but Professor Chinnery says it is likely to occur within the mother’s egg cells.

When the team looked at sequences taken from 12,500 tumour samples, they found that mitochondrial DNA was even more common in tumour DNA, arising in around one in 1,000 cancers, and in some cases, the mitochondrial DNA inserts actually causes the cancer.

“Our nuclear genetic code is breaking and being repaired all the time,” said Professor Chinnery. “Mitochondrial DNA appears to act almost like a Band-Aid, a sticking plaster to help the nuclear genetic code repair itself. And sometimes this works, but on rare occasions if might make things worse or even trigger the development of tumours.”

More than half (58%) of the insertions were in regions of the genome that code for proteins. In the majority of cases, the body recognises the invading mitochondrial DNA and silences it in a process known as methylation, whereby a molecule attaches itself to the insert and switches it off. A similar process occurs when viruses manage to insert themselves into our DNA. However, this method of silencing is not perfect, as some of the mitochondrial DNA inserts go on to be copied and move around the nucleus itself.

̽��ֱ��team looked for evidence that the reverse might happen – that mitochondrial DNA absorbs parts of our nuclear DNA – but found none. There are likely to be several reasons why this should be the case.

Firstly, cells only have two copies of nuclear DNA, but thousands of copies of mitochondrial DNA, so the chances of mitochondrial DNA being broken and passing into the nucleus are much greater than the other way around.

Secondly, the DNA in mitochondria is packaged inside two membranes and there are no holes in the membrane, so it would be difficult for nuclear DNA to get in. By contrast, if mitochondrial DNA manages to get out, holes in the membrane surrounding nuclear DNA would allow it pass through with relative ease.

Professor Sir Mark Caulfield, Vice Principal for Health at Queen Mary ̽��ֱ�� of London, said: “I am so delighted that the 100,000 Genomes Project has unlocked the dynamic interplay between mitochondrial DNA and our genome in the cell’s nucleus. This defines a new role in DNA repair, but also one that could occasionally trigger rare disease, or even malignancy.”

̽��ֱ��research was mainly funded by the Medical Research Council, Wellcome, and the National Institute for Health Research.

Reference
Wei, E et al. Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes. Nature; 5 Oct 2022; DOI: 10.1038/s41586-022-05288-7

Scientists have shown that in one in every 4,000 births, some of the genetic code from our mitochondria – the ‘batteries’ that power our cells – inserts itself into our DNA, revealing a surprising new insight into how humans evolve.

Mitochondrial DNA appears to act almost like a Band-Aid, a sticking plaster to help the nuclear genetic code repair itself. And sometimes this works, but on rare occasions if might make things worse or even trigger the development of tumours

Patrick Chinnery

Dr David Furness

Mitochondria surrounded by cytoplasm

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̽��ֱ��doctor turned detective investigating the imprints of cancer

cg605 — Mon, 15 Aug 2022 12:56:04 +0000

Self-confessed ‘nerd’ Serena Nik-Zainal went from hospital wards to the laboratory on a mission to provide patients with the best possible treatment for their illnesses. Ten years later she is at the forefront of genomic research, creating tools for clinicians which are transforming patient care.