̽��ֱ�� of Cambridge - Department of Genetics

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.

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System to auto-detect new variants will inform better response to future infectious disease outbreaks

jg533 — Wed, 01 Jan 2025 16:00:35 +0000

̽��ֱ��new approach uses samples from infected humans to allow real-time monitoring of pathogens circulating in human populations, and enable vaccine-evading bugs to be quickly and automatically identified. This could inform the development of vaccines that are more effective in preventing disease.

̽��ֱ��approach can also quickly detect emerging variants with resistance to antibiotics. This could inform the choice of treatment for people who become infected – and try to limit the spread of the disease.

It uses genetic sequencing data to provide information on the genetic changes underlying the emergence of new variants. This is important to help understand why different variants spread differently in human populations.

There are very few systems in place to keep watch for emerging variants of infectious diseases, apart from the established COVID and influenza surveillance programmes. ̽��ֱ��technique is a major advance on the existing approach to these diseases, which has relied on groups of experts to decide when a circulating bacteria or virus has changed enough to be designated a new variant.

By creating ‘family trees’, the new approach identifies new variants automatically based on how much a pathogen has changed genetically, and how easily it spreads in the human population – removing the need to convene experts to do this.

It can be used for a broad range of viruses and bacteria and only a small number of samples, taken from infected people, are needed to reveal the variants circulating in a population. This makes it particularly valuable for resource-poor settings.

̽��ֱ��report was published in the journal Nature.

“Our new method provides a way to show, surprisingly quickly, whether there are new transmissible variants of pathogens circulating in populations – and it can be used for a huge range of bacteria and viruses,” said Dr Noémie Lefrancq, first author of the report, who carried out the work at the ̽��ֱ�� of Cambridge’s Department of Genetics.

Lefrancq, who is now based at ETH Zurich, added: “We can even use it to start predicting how new variants are going to take over, which means decisions can quickly be made about how to respond.”

“Our method provides a completely objective way of spotting new strains of disease-causing bugs, by analysing their genetics and how they’re spreading in the population. This means we can rapidly and effectively spot the emergence of new highly transmissible strains,” said Professor Julian Parkhill, a researcher in the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine who was involved in the study.

Testing the technique

̽��ֱ��researchers used their new technique to analyse samples of Bordetella pertussis, the bacteria that causes whooping cough. Many countries are currently experiencing their worst whooping cough outbreaks of the last 25 years. It immediately identified 3 new variants circulating in the population that had been previously undetected.

“ ̽��ֱ��novel method proves very timely for the agent of whooping cough, which warrants reinforced surveillance given its current comeback in many countries and the worrying emergence of antimicrobial resistant lineages,” said Professor Sylvain Brisse, Head of the National Reference Center for whooping cough at Institut Pasteur, who provided bioresources and expertise on Bordetella pertussis genomic analyses and epidemiology.

In a second test, they analysed samples of Mycobacterium tuberculosis, the bacteria that causes Tuberculosis. It showed that 2 variants with resistance to antibiotics are spreading.

“ ̽��ֱ��approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible,” said Professor Henrik Salje in the ̽��ֱ�� of Cambridge’s Department of Genetics, senior author of the report.

He added: “If we see a rapid expansion of an antibiotic-resistant variant, then we could change the antibiotic that’s being prescribed to people infected by it, to try and limit the spread of that variant.”

̽��ֱ��researchers say this work is an important piece in the larger jigsaw of any public health response to infectious disease.

A constant threat

Bacteria and viruses that cause disease are constantly evolving to be better and faster at spreading between us. During the COVID pandemic, this led to the emergence of new strains: the original Wuhan strain spread rapidly but was later overtaken by other variants, including Omicron, which evolved from the original and were better at spreading. Underlying this evolution are changes in the genetic make-up of the pathogens.

Pathogens evolve through genetic changes that make them better at spreading. Scientists are particularly worried about genetic changes that allow pathogens to evade our immune system and cause disease despite us being vaccinated against them.

“This work has the potential to become an integral part of infectious disease surveillance systems around the world, and the insights it provides could completely change the way governments respond,” said Salje.

̽��ֱ��research was primarily funded by the European Research Council.

Reference: Lefrancq, N et al: ‘Learning the fitness dynamics of pathogens from phylogenies.’ January 2025, DOI: 10.1038/s41586-024-08309-9

Researchers have come up with a new way to identify more infectious variants of viruses or bacteria that start spreading in humans – including those causing flu, COVID, whooping cough and tuberculosis.

̽��ֱ��approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible.

Henrik Salje

Milan Krasula on Getty

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̽��ֱ��master of mutations

lkm37 — Mon, 29 Jul 2024 13:39:02 +0000

Dr Alex Cagan – illustrator, geneticist and explorer of animal DNA – is offering a new perspective on the tapestry of life. His work has profound implications for the pursuit of healthy ageing and the possibilities of cancer resistance.

Birth by C-section more than doubles odds of measles vaccine failure

jg533 — Mon, 13 May 2024 09:01:04 +0000

A study by the ̽��ֱ�� of Cambridge, UK, and Fudan ̽��ֱ��, China, has found that a single dose of the measles jab is up to 2.6 times more likely to be completely ineffective in children born by C-section, compared to those born naturally.

Failure of the vaccine means that the child’s immune system does not produce antibodies to fight against measles infection, so they remain susceptible to the disease.

A second measles jab was found to induce a robust immunity against measles in C-section children.

Measles is a highly infectious disease, and even low vaccine failure rates can significantly increase the risk of an outbreak.

A potential reason for this effect is linked to the development of the infant’s gut microbiome – the vast collection of microbes that naturally live inside the gut. Other studies have shown that vaginal birth transfers a greater variety of microbes from mother to baby, which can boost the immune system.

“We’ve discovered that the way we’re born - either by C-section or natural birth - has long-term consequences on our immunity to diseases as we grow up,” said Professor Henrik Salje in the ̽��ֱ�� of Cambridge’s Department of Genetics, joint senior author of the report.

He added: “We know that a lot of children don't end up having their second measles jab, which is dangerous for them as individuals and for the wider population.

“Infants born by C-section are the ones we really want to be following up to make sure they get their second measles jab, because their first jab is much more likely to fail.”

̽��ֱ��results are published today in the journal Nature Microbiology.

At least 95% of the population needs to be fully vaccinated to keep measles under control but the UK is well below this, despite the Measles, Mumps and Rubella (MMR) vaccine being available through the NHS Routine Childhood Immunisation Programme.

An increasing number of women around the world are choosing to give birth by caesarean section: in the UK a third of all births are by C-section, in Brazil and Turkey over half of all children are born this way.

“With a C-section birth, children aren’t exposed to the mother’s microbiome in the same way as with a vaginal birth. We think this means they take longer to catch up in developing their gut microbiome, and with it, the ability of the immune system to be primed by vaccines against diseases including measles,” said Salje.

To get their results, the researchers used data from previous studies of over 1,500 children in Hunan, China, which included blood samples taken every few weeks from birth to the age of 12. This allowed them to see how levels of measles antibodies in the blood change over the first few years of life, including following vaccination.

They found that 12% of children born via caesarean section had no immune response to their first measles vaccination, as compared to 5% of children born by vaginal delivery. This means that many of the children born by C-section did still mount an immune response following their first vaccination.

Two doses of the measles jab are needed for the body to mount a long-lasting immune response and protect against measles. According to the World Health Organisation, in 2022 only 83% of the world's children had received one dose of measles vaccine by their first birthday – the lowest since 2008.

Salje said: “Vaccine hesitancy is really problematic, and measles is top of the list of diseases we’re worried about because it’s so infectious.”

Measles is one of the world’s most contagious diseases, spread by coughs and sneezes. It starts with cold-like symptoms and a rash, and can lead to serious complications including blindness, seizures, and death.

Before the measles vaccine was introduced in 1963, there were major measles epidemics every few years causing an estimated 2.6 million deaths each year.

̽��ֱ��research was funded by the National Natural Science Foundation of China.

Reference

Wang, W et al: ‘Dynamics of measles immunity from birth and following vaccination.’ Nature Microbiology, 13 May 2024. DOI: 10.1038/s41564-024-01694-x

Researchers say it is vital that children born by caesarean section receive two doses of the measles vaccine for robust protection against the disease.

CHBD / E+ / Getty Images

Very sick 5 year old little boy fighting measles infection, boy is laying in bed under the blanket with an agonizing expression, boy is covered with rash caused by virus.

Yes

Ageing: can we add more life to our years?

jg533 — Wed, 20 Dec 2023 08:59:28 +0000

Research advances at the ̽��ֱ�� of Cambridge mean that the eternal quest to reverse the march of time may soon become a reality.

Four Cambridge researchers awarded consolidator grants from the European Research Council

cg605 — Wed, 22 Nov 2023 12:54:39 +0000

̽��ֱ��grants are part of the European Union’s Horizon Europe programme. They are given to excellent scientists and scholars at the career stage to support them to pursue their most promising scientific ideas.

Cambridge scientists, Professor Chiara Ciccarelli, Professor Rosana Collepardo-Guevara, Professor Jason Miller, and Dr Jenny Zhang have been named as awardees of ERC consolidator grants.

Professor Chiara Ciccarelli

Chiara Ciccarelli is Professor of Physics at the Cavendish Laboratory at the Department of Physics. She is a Royal Society ̽��ֱ�� Research Fellow and a Fellow and Director of Studies at St Catharine's College. She said: “Our group studies magnets and seeks ways to write and read their magnetic state as fast and as energy-efficiently as possible. This is because magnets remain the best way, that we know of, to store digital data for a long time.

“Our ERC project, PICaSSO, explores new ways to ‘write’ magnets at low temperature by interfacing them with superconductors. Although this research is still at an early stage, it would allow the development of ultra-energy-efficient cryogenic memories, a necessary requirement for the realistic scaling of quantum computers.

“I am absolutely delighted to have been awarded a consolidator grant. It is an incredible opportunity to do great science and an important recognition of the work of my amazing team.”

Professor Rosana Collepardo-Guevara

Rosana Collepardo-Guevara is Professor of Computational and Molecular Biophysics at the Yusuf Hamied Department of Chemistry and the Department of Genetics. She is a Winton Advanced Research Fellow in physics, a director of postgraduate education for chemistry and a Fellow of Clare College. She said: “My group investigates the connection between genome structure and function by developing computer models and algorithms that can bridge scales, from atoms to genes, while considering the extensive chemical diversity of the genome.

“We will investigate the transformative hypothesis of phase transitions in genome organisation, which suggests that our genes are organised inside functionally diverse liquid drops. We will develop new computer models to probe how the physical properties of these droplets are regulated, and how this may contribute to the tight regulation of our genes.

“I am truly delighted and proud of my team. This success is owed to the exceptional students and postdocs that I’ve had the privilege to supervise over the years, and also to the support of my mentors, collaborators, and family. This grant will give us the opportunity to keep exploring radical ideas.”

Professor Jason Miller

Jason Miller is a professor in the Statistics Laboratory and a Fellow of Trinity College. He said: “My research is at the interface of probability theory with complex analysis, combinatorics, and geometry. ̽��ֱ��questions I study arise from models in statistical physics which are exactly at a critical point between a phase transition.

“My ERC project will be investigating critical random media in two dimensions, including models of how fluid flows through a porous medium and how the spins organise themselves in a magnet. ̽��ֱ��focus will be the study of their fractal structure and diffusion properties.

“I am very pleased to have received the grant. With the support that it provides, I will be able to form a research group to tackle longstanding questions in the area.”

Dr Jenny Zhang

Dr Jenny Zhang is a BBSRC David Phillips Research Fellow at the Yusuf Hamied Department of Chemistry. She is a Fellow of Corpus Christi College. She said: “My team focuses on creating toolsets for rewiring the electrochemical pathways associated with living systems, particularly photosynthetic organisms. We do this to better understand fundamental bioenergetics and to manipulate them for various applications, such as in renewable energy generation.

“This ERC project develops an exciting new approach for accelerating the creation of synergistic interactions between biological and non-biological materials for highly efficient and robust energy exchange. ̽��ֱ��ultimate aim is to generate high performing biohybrid materials for clean energy generation.

“I am absolutely thrilled to be awarded this unique grant, which recognises all the key ingredients needed for innovation. This wonderful result was a cumulation of a lot of hard work, but also the generous support of my wonderful team and colleagues. I could not be more grateful for both the grant and the people I get to work with.”

Scientists at UK institutions have won the second greatest number of grants in Europe. Across Europe, the number of women receiving grants has increased for the third year running.

“I extend my heartfelt congratulations to all the brilliant researchers who have been selected for ERC Consolidator Grants,” said Iliana Ivanova, European Commissioner for Innovation, Research, Culture, Education and Youth. “I'm especially thrilled to note the significant increase in the representation of women among the winners for the third consecutive year in this prestigious grant competition. This positive trend not only reflects the outstanding contributions of women researchers but also highlights the strides we are making towards a more inclusive and diverse scientific community.”

̽��ֱ��ERC, set up by the European Union in 2007, is the premier European funding organisation for excellent frontier research. It funds creative researchers of any nationality and age, to run projects based across Europe.

̽��ֱ��European Research Council (ERC) has awarded grants worth a total of €627 million to 308 researchers across Europe, of whom four are at the ̽��ֱ�� of Cambridge.

This grant will give us the opportunity to keep exploring radical ideas.

Professor Rosana Collepardo-Guevara

Jenny Zhang - Nathan Pitt, ̽��ֱ�� of Cambridge

Left to right: Professor Chiara Ciccarelli, Professor Jason Miller, Professor Rosana Collepardo-Guevara, and Dr Jenny Zhang

̽��ֱ��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.

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Scientists discover secret of virgin birth, and switch on the ability in female flies

jg533 — Fri, 28 Jul 2023 15:04:16 +0000

For the first time, scientists have managed to induce virgin birth in an animal that usually reproduces sexually: the fruit fly Drosophila melanogaster.

Once induced in this fruit fly, this ability is passed on through the generations: the offspring can reproduce either sexually if there are males around, or by virgin birth if there aren’t.

For most animals, reproduction is sexual - it involves a female’s egg being fertilised by a male’s sperm. Virgin birth, or ‘parthenogenesis’, is the process by which an egg develops into an embryo without fertilisation by sperm – a male is not needed.

̽��ֱ��offspring of a virgin birth are not exact clones of their mother but are genetically very similar, and are always female.

“We’re the first to show that you can engineer virgin births to happen in an animal – it was very exciting to see a virgin fly produce an embryo able to develop to adulthood, and then repeat the process,” said Dr Alexis Sperling, a researcher at the ̽��ֱ�� of Cambridge and first author of the paper.

She added: “In our genetically manipulated flies, the females waited to find a male for half their lives - about 40 days - but then gave up and proceeded to have a virgin birth.”

In the experiments, only 1-2% of the second generation of female flies with the ability for virgin birth produced offspring, and this occurred only when there were no male flies around. When males were available, the females mated and reproduced in the normal way.

Switching to a virgin birth can be a survival strategy: a one-off generation of virgin births can help to keep the species going.

̽��ֱ��study is published in the journal Current Biology.

To achieve their results, researchers first sequenced the genomes of two strains of another species of fruit fly, called Drosophila mercatorum. One strain needs males to reproduce, the other reproduces only through virgin birth. They identified the genes that were switched on, or switched off, when the flies were reproducing without fathers.

With the candidate genes for virgin birth ability identified in Drosophila mercatorum, the researchers altered what they thought were the corresponding genes in the model fruit fly, Drosophila melanogaster. It worked: Drosophila melanogaster suddenly acquired the ability for virgin birth.

̽��ֱ��research involved over 220,000 virgin fruit flies and took six years to complete.

Key to the discovery was the fact that this work was done in Drosophila melanogaster – the researchers say it would have been incredibly difficult in any other animal. This fly has been the ‘model organism’ for research in genetics for over 100 years and its genes are very well understood.

Sperling, who carried out this work in the Department of Genetics, has recently moved to Cambridge Crop Science Centre to work on crop pests and hopes to eventually investigate why virgin birth in insects may be becoming more common, particularly in pest species.

“If there’s continued selection pressure for virgin births in insect pests, which there seems to be, it will eventually lead to them reproducing only in this way. It could become a real problem for agriculture because females produce only females, so their ability to spread doubles,” said Sperling.

̽��ֱ��females of some egg-laying animals – including birds, lizards and snakes, can switch naturally to give birth without males. But virgin birth in animals that normally sexually reproduce is rare, often only observed in zoo animals, and usually happens when the female has been isolated for a long time and has little hope of finding a mate.

̽��ֱ��research was funded by the Leverhulme Trust.

Reference

Sperling, A L et al.: ‘A genetic basis for facultative parthenogenesis in Drosophila.’ Current Biology, July 2023. DOI: 10.1016/j.cub.2023.07.006

Scientists have pinpointed a genetic cause for virgin birth for the first time, and once switched on the ability is passed down through generations of females.

It was very exciting to see a virgin fly produce an embryo able to develop to adulthood

Alexis Sperling

Jose Casal and Peter Lawrence

Fruit fly, Drosophila mercatorum

̽��ֱ��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.

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King's Birthday Honours 2023

sc604 — Sat, 17 Jun 2023 08:44:22 +0000

Leaders in fields from economics to history are among the Cambridge academics recognised in the King's first birthday honours list.