Ancient DNA analysis uncovers Ukraine’s intricate genetic history

Posted on January 15, 2025 by Igor Mitreski

To study the history of migration and movement in the Ukrainian region, with a particular focus on Iron Age and Medieval migrant populations, the scientists generated genomic data on 91 individuals from around 7000 BC to around 1800 AD. Their results show that ancient peoples had diverse ancestry as a result of frequent migration, assimilation, and contact.

A map showing the geographical location of the ancient figures included in the study and a chronology showing the dates of the figures in the archaeological group. Image credit: Saag others., doi: 10.1126/sciadv.adr0695.

Over the centuries, migration has taken place in the steppe and forest-steppe regions of Ukraine in several directions.

These migrations were driven by a variety of processes, including cultural contacts and conflicts between tribes, trade, demographic pressures, and the expansion of nomadic areas of influence.

The main migration flows were from the Carpathian-Donabian region, the Southern Ural-Volga region, Central Asia and the North Caucasus, and intensive population movements also occurred within the territory of Ukraine.

At the end of the Bronze Age and the beginning of the Early Iron Age, the most notable archaeological activity in the northern Pontic Steppe was Cimmerian and military operations in Asia Minor.

The Cimmerians were followed by Scythians and SarmatiansEarly Iron Age political and military tribal confederations with various combinations of local and East Asian ancestry, as shown by previous ancient DNA (aDNA) studies. At this time, the northern Black Sea coast was covered with a network of urbanized Greek colonies.

In the forest-steppe region, the modern sedentary population is influenced by the former Tsinets culture (including the Lusatian and Vysotska cultures) and the central European influences of the Hallstatt and La Tène periods (Illyrians, Thracians, Celts). It was related.

According to written and archaeological sources, the peoples considered to be the predecessors of the Slavs were Zarbinetska culture — Already existed in the Ukrainian region from the 3rd century BC onwards, during the La Tène and Roman times.

The beginning of the era of migration in the Ukrainian region is associated with the arrival of Germanic tribes such as the Goths and the formation of a multiethnic state. Culture of Cherniahivwhich also included other ethnic groups that already lived in the area.

Between the 2nd and 4th centuries AD, the nomadic Huns of Central Asia emerged on the northern Pontic Steppe, and their westward migration brought about significant economic, cultural, and social changes in Europe.

This period is associated with the emergence of a new ethnolinguistic group, the Slavs, who spread across much of Eastern Europe between the 5th and 7th centuries AD.

From the 8th to the 10th century AD, large parts of Ukraine were under its control. Khazar Khaganate.

In Ukrainian archeology, this is expressed as follows: saltive cultureit is believed that it was shared among multiple ethnic groups (Alans, Bulgars, Turks, Slavs, Magyars, etc.).

At the same time, there was a process of unification of the Slavic tribes, and in the 9th century AD, Kiev Rus was formed.

The development of Slavic states took place against the background of constant nomadic invasions from the east.

Between the 11th and 13th centuries AD, waves of Pechenegs, Turks, and Cumans invaded the northern Pontic region from Central Asia. The most substantial invasion in terms of military power and results was that of the Mongols of the Golden Horde. 13th century AD.

By the 15th century AD, remnants of the Golden Horde, such as the Nogai, still lived in the steppes of northern Pontus.

Since the 16th century. In the Western era, Slavs were the majority ethnolinguistic group in the Ukrainian region.

“We decided to investigate the genetic ancestry of people who lived in the northern Pontic region during these times and were associated with different cultural groups,” said lead author of the study and co-author of the University of Tartu and University of Tartu. said Dr. Letty Saag, a researcher at College London. And my colleagues.

For the study, the authors extracted and sequenced DNA from tooth roots and bone fragments from 91 people at 33 archaeological sites in present-day Ukraine.

The sample included one Neolithic individual (7000–6000 BC), nine individuals from the Bronze Age and the beginning of the Final Bronze Age to the beginning of the Iron Age (3000–700 BC), and six individuals from the beginning of the Early Iron Age. contained the name (900-700 BC), 29 people of the Early Iron Age Scythian period (700-300 BC), 6 people of the Early Iron Age (700-300 BC), the end of the Iron Age (400-1 BC). , 12 from the Late Iron Age (1-400 AD), 9 from the Early Middle Ages (800-900 AD), and from the Middle Ages to B.C. 19 Early modern period (900 to 1800 AD).

Their DNA analysis shows that ancient peoples had diverse ancestry as a result of frequent migration, assimilation, and contact.

“From the Mesolithic to the time of the Vysotska and Vylozerska cultures at the end of the Bronze Age, the proportion of large-scale ancestry was similar to modern populations in other parts of Europe, first as hunter-gatherers and then as early farmers. and finally a mixture of the two: early farmers and steppe pastoralists,” the researchers said.

“From the Cimmerian period to the Middle Ages, the appearance of eastern nomads in the Pontic region became a common occurrence.”

“Their genetic make-up ranges from Yamuna-like superimposition on indigenous peoples, such as the Scythians and Cumans, to highly East Asian ancestry and minimal indigenous ancestry, such as the Alan Bulgars and Nogais. They ranged from mixed race to mixed race.”

“At that time, nomadic groups were recorded in the steppe regions, but the people of other parts of the Ukrainian region had mainly European ancestry, with connections to local ancestors and Thracians, Greeks, Goths, etc. there were.”

“The palincest of migration and population mixing in the Ukrainian region contributes to high genetic heterogeneity in geographically, culturally and socially homogeneous populations, and between individuals from the same place, at the same time, and with the same characteristics. “Different genetic profiles will exist,” they added.

“Our study focuses specifically on historically attested migrant populations rather than local populations, and the sampling is geographically biased primarily towards eastern Ukraine and temporally towards the Iron Age and Middle Ages. It is important to note that

“Nevertheless, a large local genetic profile similar to modern Ukrainians persists in the region through time and within this sample set.”

“This ancestral structure can be traced back at least to the Zurbunas, and is also found in the Vysotskas and Lusatians, the Scythians of the west, the modern agricultural peoples of the east, the Chernyahivs, and even the medieval and early modern Slavs.”

“We infer that there has been a major indigenous component in the ancestry of Ukrainians since at least the Bronze Age, although there are clear traces of high migration activity, including immigration from East Asia and extensive admixture. ”

of findings Featured in this week's diary scientific progress.

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Letty Thurg others. 2025. Crossroads of the Northern Pontus: Migration of Ukraine from the Bronze Age to the Early Modern Period. scientific progress 11(2);doi: 10.1126/sciadv.adr0695

Source: www.sci.news

Shared DNA Mutations Impacting the Genome in Cancer Cells

Posted on December 2, 2024 by Igor Mitreski

The human genome consists of approximately 3 billion DNA base pairs. If these base pairs were letters grouped together on a single line, they would fill more than 6,000 novels, too large to fit in a cell. Instead, some proteins organize and reform DNA into a more functional 3D structure called DNA. chromatin. These proteins regulate how different parts of the genome interact, controlling which genes are activated and which remain silent within each cell. One such protein is CCCTC binding factor or CTCF.

For CTCF to work, it must first bind to a specific spot on the DNA called CTCF. binding site. Scientists report that these CTCF binding sites behave differently in each scenario. Some lose their binding ability due to chemical interactions within the DNA, while others remain stable. Scientists call something stable Persistent CTCF binding site.

Scientists have previously reported that mutations in CTCF binding sites are common in cancer cells and disrupt the normal 3D structure of the genome. However, it was unclear whether these mutations were concentrated at persistence sites or what role they played. Australian researchers sought to understand mutations in persistent CTCF binding sites and how they affect different cancers.

To address these questions, the research team developed a computational tool based on machine learning models. CTCF-INSITE. Their tool uses genetic data and the interactions of organic compounds such as methyl in the genome to predict which CTCF binding sites are likely to persist even as CTCF protein levels decline. Researchers will use this tool to determine which persistent CTCF binding sites across the genome may be particularly vulnerable to mutations and whether these mutations are associated with cancer growth. I mapped it.

Using data from several human cell culture samples, including prostate cancer cells, breast cancer cells, and lung cancer cells, researchers developed a tool that allows them to distinguish between stable and unstable CTCF binding sites. trained. They exploited characteristics such as protein binding strength, the relative location of binding sites within the genome, and how distant regions of DNA interact to produce proteins.

The researchers then looked at mutation data from 12 types of cancer. International Cancer Genome Consortium. To avoid imbalance, we filtered out data entries with too few or too many mutations. Next, we applied CTCF-INSITE. A tool to test whether persistent CTCF binding sites are more likely to mutate in cancer cells than other CTCF binding sites.

They found significantly more mutations in persistent CTCF binding sites in all cancer types examined. This means that there were more mutations at these sites than would be expected by random chance. The researchers noted that the mutations were specific to the CTCF binding site, rather than in parts of the DNA close to it. They also reported that these mutations were more prominent in breast and prostate cancer cells than in other types of cancer.

The researchers also sought to understand whether these mutations alter the 3D structure of the genome. Using experimental techniques such as fluorescence imaging, they examined some of these cancer-specific mutations and found that many of them alter the genome structure and reduce the strength and effectiveness of CTCF binding. It turned out that. They explained that this reduction could affect gene expression in a way that promotes cancer growth.

The researchers emphasized that their findings were not limited to one or two types of cancer, as similar results were found for stomach, lung, prostate, breast and skin cancers. Although the exact mutation patterns vary between cancers, persistent CTCF binding sites were reported to have consistently higher mutations overall.

The researchers concluded that their findings may help other cancer researchers understand similarities in the onset and progression of multiple cancer types. They also proposed that their machine learning tools could provide future researchers with CTCF binding site candidates relevant to experiments investigating undocumented causes of cancer.

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Source: sciworthy.com

The Regretful Decision: Surrendering My DNA to 23andMe Only to Discover My British Heritage

Posted on November 30, 2024 by Igor Mitreski

23andMe is currently in crisis. The once-promising genetic testing company has experienced a significant downfall, with a 98% loss in its $6 billion value, the departure of all independent directors, a reduction in nearly half of its employees, and a decline in its customer base from 15 million. is urgently working to delete DNA data from its records. I am one of the affected individuals.

My journey with 23andMe began hesitantly in 2016 when I ordered their kit by mail. After some delay, I finally submitted my genetic sample for analysis. As a tech journalist, I am cautious about sharing data with companies, especially genetic information, which is immutable unlike passwords or credit card details.

The results revealed that I am 63% British and Irish, and 17% Danish, confirming my extensive northwestern European heritage. However, the absence of my supposed Czech lineage was surprising. With 23andMe’s uncertain future and concerns about the fate of user data, I reflect on the exchange of genetic privacy for such information.

Timothy Caulfield, a University of Alberta professor, notes that many individuals, like myself, experience ambivalence upon receiving genetic test results.

The concept of genetic testing to uncover ancestral roots and its implications on personal identity has always troubled me. Caulfield, who faced similar concerns with his own ancestry, argues that the notion of genetic influence on individual identity perpetuates racism.

Marketing strategies played a significant role in the success of companies like 23andMe. However, the impact of genetic testing results on one’s sense of identity can vary drastically, from affirming to challenging deeply held beliefs.

As 23andMe’s future remains uncertain, questions arise regarding the handling of existing user data. The ethical implications of genetic information extend beyond personal privacy to potentially compromising the privacy of relatives.

To safeguard my data, I opted to delete my account and requested a copy of my genetic information. However, concerns persist about the retention of such data by the company, especially in case of bankruptcy or ownership changes.

23andMe’s commitment to customer data protection is emphasized, with assurances of maintaining privacy standards even amidst financial instability.

Receiving my genetic data opened up new insights into my heritage, but the challenge lies in interpreting the vast amount of genomic information provided. Despite this, I have not taken any actions based on this data, as the complexity of genetic identity remains a source of ambivalence and uncertainty.

Source: www.theguardian.com

New DNA evidence from Pompeii challenges prior beliefs about ash-covered victims

Posted on November 8, 2024 by Igor Mitreski

After centuries, it has been discovered that long-standing beliefs about some of the inhabitants of Pompeii were not as accurate as previously thought.

Recent DNA analysis of human remains from the ancient Roman town destroyed by the eruption of Mount Vesuvius in 79 AD has shown that some victims were misidentified, challenging modern assumptions. This has shed light on how historical data is viewed in the past.

The authors of the study published in the journal Science on Thursday wrote, “We have found that traditional interpretations regarding an individual’s gender and familial connections do not align with the new evidence.” They also added, “It is not always reliable to apply modern gender norms when interpreting historical information.”

Archaeologists in Pompeii famously immortalized the victims by using plaster to recreate their bodies, leading to various stories being told about them. For example, it was believed for a long time that two women died embracing each other and a mother was found holding her child.

However, the new DNA analysis revealed that the individual thought to be the child’s mother was actually an unrelated man. Additionally, at least one of the individuals believed to be sisters or mother and daughter were actually both men.

Professor David Reich, one of the authors of the study, warned about the dangers of inventing stories about gender and family relationships in ancient societies based on present-day expectations.

The study involved researchers from the University of Florence in Italy and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. They used preserved genetic material to determine the gender, ancestry, and genetic relationships of the victims by examining 14 casts that had been preserved for about 2000 years.

Their findings also showed that the residents of Pompeii were diverse, with ancestral roots primarily traced back to immigrants from the Eastern Mediterranean. This underscores the multicultural nature of the city and its inhabitants.

Mount Vesuvius had been mostly inactive before the catastrophic eruption that lasted over 24 hours with devastating power. The eruption buried Pompeii, home to an estimated 20,000 people, under layers of ash, pumice, and mud, preserving the city for centuries.

Pompeii remained buried and forgotten until its rediscovery in 1748. In the 19th century, archaeologists used a technique to create casts of the victims by pouring plaster into the voids left by decomposed bodies, resulting in lifelike molds that captured the victims’ final moments.

Ongoing research on Pompeii continues to unveil new insights into the ancient city and its inhabitants. Recent discoveries, such as using artificial intelligence to decipher a charred scroll and the unveiling of a luxurious home, highlight the constant exploration of Pompeii’s history.

Source: www.nbcnews.com

Pompeii Burials Reveal New Insights Through DNA Analysis

Posted on November 8, 2024 by Igor Mitreski

Plaster statues of those who died at Pompeii. DNA testing revealed that the adult on the right was a man unrelated to the young child in his lap.

Pompeii Archaeological Park

Genetic testing has revealed that a plaster cast in Pompeii was not the person it was assumed to be, highlighting how idealized narratives can be projected onto archaeological evidence.

The analysis also revealed that Pompeii's demographics were also much more complex and diverse than previously thought.

When Mount Vesuvius erupted in 79 AD, several Roman towns were buried, including Pompeii. Many of Pompeii's inhabitants were completely suffocated by the compressed ash during the eruption, and as their bodies decomposed, cavities formed, perfectly preserving their positions in their final moments.

in 19 years^th In the century, archaeologists developed a method of pouring plaster into cavities to create lifelike castings. Since then, more than 100 of these castings have been made, preserving the victims' shapes and bones that have remained undecomposed for centuries.

But it says it has long been known that many of the plaster statues were worked into different poses, sometimes placed together, to add drama to the story of Pompeii. Valeria Amoretti At the Archaeological Park of Pompeii in Naples, Italy.

To learn more about who these people were, Amoretti and colleagues examined 14 plaster casts and extracted DNA from the bones of five of them.

What they discovered completely changed the established interpretation of who they were. It was long believed that an adult wearing a gold bracelet and carrying a child on her lap was the child's mother. DNA analysis revealed that they were actually adult males and were not biologically related to the child. A nearby person previously interpreted to be the father was also unrelated to the child, who was assumed to be the mother.

Another pair, believed to be sisters or mother and daughter who died in an embrace, also included at least one genetic male, making them unlikely to be related.

Genetic analysis further revealed that the people of Pompeii had a diverse ancestry, including elements related to modern-day Jewish populations in the eastern Mediterranean, the Levant, and North Africa.

Amoretti says it's no surprise that the Roman world was multicultural and that the Mediterranean Sea and its ports brought people together.

“But discovering the extent of this melting pot, even in an average provincial city like Pompeii, and getting scientific evidence of it from ancient DNA is very interesting,” she says.

Alyssa Mitnik Researchers at Harvard University say the study highlights the importance of applying science before interpreting archeology at face value.

“Ultimately, it reminds us that the most intuitive, dramatic, sensational explanations aren't always the truth, and encourages us to recognize and question our preconceptions,” she says. .

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Source: www.newscientist.com

Scientists explore the mechanisms of DNA methylation in plants

Posted on November 6, 2024 by Igor Mitreski

DNA methylation is one of several epigenetic mechanisms important for controlling gene expression in eukaryotes.

Arabidopsis. Image credit: Carl Davies, CSIRO/CC BY 3.0.

DNA methylation is a normal biological process in living cells in which small chemical groups called methyl groups are added to DNA.

This activity controls which genes are turned on or off, which affects a variety of characteristics, including how the organism responds to its environment.

Part of this job involves silencing, or turning off, certain pieces of DNA moving around in an organism’s genome.

These so-called jumping genes, or transposons, can cause damage if left unregulated.

This entire process is controlled by enzymes, but mammals and plants have developed different enzymes to add methyl groups.

“Mammals only have two major enzymes that add methyl groups in one DNA context, whereas plants actually have multiple enzymes that do it in three DNA contexts.” said researcher Professor Xuehua Zhong. Washington University in St. Louis.

“This is the focus of our research. The question is: why do plants need extra methyltransferases?”

“A particular gene or combination of genes contributes to a particular characteristic or trait.”

“If we know exactly how they are regulated, we can find ways to innovate techniques for crop improvement.”

Professor Zhong and his colleagues focused on two enzymes specifically found in plants: CMT3 and CMT2.

Both enzymes are responsible for adding methyl groups to DNA, but CMT3 specializes in one part of DNA called CHG sequences, and CMT2 specializes in another part called CHH sequences.

Despite their functional differences, both enzymes are part of the same chromomethylase (CMT) family and have evolved through duplication events that provide plants with additional copies of genetic information.

We use a common model plant called Thale cress (Arabidopsis), the study authors investigated how these duplicated enzymes evolved different functions over time.

They found that somewhere along the evolutionary timeline, CMT2 lost the ability to methylate CHG sequences. This is because it lacks an important amino acid called arginine.

“Arginine is special because it has an electric charge,” says Jia Gwee, a graduate student at Washington University in St. Louis.

“Because it is positively charged inside cells, it can form hydrogen bonds and other chemical interactions with negatively charged DNA, for example.”

“However, CMT2 contains a different amino acid, valine. Valine is uncharged and therefore cannot recognize CHG contexts like CMT3. We think that is the reason for the difference between the two enzymes. Masu.”

To confirm this evolutionary change, the researchers used a mutation to move arginine back into CMT2.

As expected, CMT2 was able to methylate both CHG and CHH. This suggests that CMT2 is originally a duplicate of CMT3, a backup system to offload as DNA becomes more complex.

“But instead of just copying the original functionality, we developed something new,” Professor Zhong said.

This study also provided insight into the unique structure of CMT2.

This enzyme has a long, flexible N-terminus that controls the stability of its protein.

“This is one of the ways plants have evolved to increase genome stability and combat environmental stress,” Professor Zhong said.

“This feature may explain why CMT2 has evolved in plants growing in very diverse conditions around the world.”

of result Published in today’s diary scientific progress.

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Gwee Others. 2024. scientific progressin press. doi: 10.1126/sciadv.adr2222

Source: www.sci.news

DNA analysis confirms the identity of ‘Wellman’ skeleton with an 800-year-old Norwegian tale

Posted on October 26, 2024 by Igor Mitreski

Complete skeletal remains of “Wellman”

Eiji Hojem, NTNU University Museum

Researchers now believe they have identified the remains of a Norwegian story written more than 800 years ago that depicts a dead man being thrown into a castle well.

The Sverris Saga is a 182-section Old Norse document that records the exploits of King Sverre Sigurdsson, who came to power in the late 12th century. In one section, it is said that rival clans who attacked Sveresborg Castle near Trondheim, Norway, “took the dead, threw them into a well, and buried them with stones.”

The well was located within the castle walls and was the only permanent source of water for the area. It has been speculated that the man thrown into the well in this story may have been suffering from a disease, and that throwing him into the well may have been an early act of biological warfare.

In 1938, part of a medieval well in the ruins of Sveresborg Castle was drained, and a skeleton was discovered beneath the rubble and rocks at the bottom. The skeleton, known as “Wellman,” was widely believed to be the remains of the person mentioned in the story, but it was impossible to confirm that at the time.

now, Anna Petersen Researchers at the Norwegian Institute for Cultural Heritage in Oslo used radiocarbon dating and DNA analysis of the remains' teeth to show that the range of dates in which the man was alive is consistent with the castle raid. . Although it's not conclusive proof that the man is the person mentioned in the story, “circumstantial evidence is consistent with this conclusion,” Pellersen said.

The Well Man's skeleton was discovered in 1938

Riksantikvaren (Norwegian Directorate General for Cultural Heritage)

Additionally, the team was able to further enrich the story. “The investigation we conducted uncovered many details about both the incident and the person that were not mentioned in the story episode,” Petersen said.

For example, DNA suggests he likely had blue eyes and blonde or light brown hair. Researchers also believe, based on comparisons with modern and ancient Norwegian DNA,
that his ancestors came from Vest Agder County, in what is now the southernmost tip of Norway.

What they couldn't find was any evidence that the men were thrown into the well because they were sick or to make drinking water unavailable, but no evidence to the contrary. can't be found, and the question remains unanswered.

michael martin The researchers at the Norwegian University of Science and Technology in Trondheim say their approach of matching historical documents with DNA evidence will help them build family trees of long-deceased royal families and “physically reveal life stories such as movements.” He states that it may also be applicable to “describing and drawing schematically.” Anonymous people whose remains were recovered from archaeological excavations across geographic regions. ”

Researchers collected DNA from one of the skeleton's teeth

Norwegian Institute of Cultural Heritage (NIKU)

“To my knowledge, this is the earliest instance in which genomic information has been recovered from a specific person, or even a specific person, described in an ancient text,” Martin said.

He says generating genomic information from ancient skeletons can provide new details about a person. “These details are not included in the original text, so genetic data enriches the story and provides a way to separate fact from fiction,” Martin says.

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Source: www.newscientist.com

New study uncovers common, mysterious I motif structure in human genome DNA

Posted on September 3, 2024 by Igor Mitreski

The so-called i-motif is a knot-like DNA structure that forms in the nuclei of human cells and is thought to provide important genome control. Garvan Institute of Medical Research Other studies have used immunoprecipitation and next-generation sequencing to identify i-motif structures in human DNA.

Peña Martinez othersIn total, we observed 53,000 i-motifs across three human cell lines (MCF7, U2OS, and HEK293T). Image courtesy of Peña Martínez. others., doi: 10.1038/s44318-024-00210-5.

The I motif is a DNA structure that differs from the iconic double helix shape.

These form when runs of cytosine letters on the same DNA strand pair up with each other to form a four-stranded twisted structure that juts out from the double helix.

In 2018, scientists at the Garvan Institute of Medical Research were the first to successfully directly visualize i-motifs inside living human cells, using new antibody tools they developed to recognise and bind to the i-motifs.

The new study expands on these findings by using the antibody to identify the location of i-motifs throughout the genome.

“In this study, we have mapped more than 50,000 i-motif sites in the human genome that are found in all three cell types we looked at,” said Professor Daniel Crist from the Garvan Institute of Medical Research, lead author of the study.

“This is a surprisingly high number for a DNA structure whose presence in cells was once a matter of debate.”

“Our findings confirm that the i-motif is not just an object of laboratory study, but is widespread and likely plays an important role in genome function.”

The researchers found that i-motifs are not scattered randomly, but are concentrated in important functional regions of the genome, including those that control gene activity.

“We found that the i-motif is associated with genes that are highly active at specific times in the cell cycle,” said lead author Cristian David Peña Martinez, PhD, also of the Garvan Medical Institute.

“This suggests that it plays a dynamic role in regulating gene activity.”

“We also discovered that i-motifs are formed in the promoter regions of cancer genes. For example, MYC Oncogenes encode one of cancer’s most notoriously ‘untreatable’ targets.”

“This opens up exciting opportunities to target disease-related genes through i-motif structures.”

“The widespread presence of the i-motif near these 'holy grail' sequences implicated in hard-to-treat cancers opens up new possibilities for novel diagnostic and therapeutic approaches,” said study co-author Sarah Kummerfeld, PhD, a researcher at the Garvan Medical Institute.

“It may be possible to design drugs that target the i-motif to affect gene expression, potentially expanding current treatment options.”

Team result Published in EMBO Journal.

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Christian David Peña Martinez othersi-motif structures are widely distributed in human genomic DNA. Embo JPublished online August 29, 2024, doi: 10.1038/s44318-024-00210-5

Source: www.sci.news

Newly Discovered DNA Methylation Sensor Uncovered by Scientists

Posted on August 29, 2024 by Igor Mitreski

DNA methylation is a widely observed epigenetic modification in biological systems that serves diverse functions in transcriptional regulation, transposable element silencing, and innate immunity.

A nucleosome composed of DNA (grey) and histones (blue) with a single hemimethylated cytosine bound by CDCA7 (purple). Image courtesy of Kyohei Arita and Kazuaki Ushi.

DNA methylation is the process by which methyl groups are added to cytosine bases in DNA molecules and is the primary way in which DNA is epigenetically marked.

Epigenetic modifications act as on-off switches that regulate gene expression, helping to generate diverse cell types without altering the underlying DNA sequence – a way for the body to ensure that brain-related genes aren’t turned on in heart cells, for example.

Therefore, maintenance of DNA methylation patterns is crucial to ensure correct and consistent function of each cell type.

However, this is not easy: DNA methylation patterns can change over time, and this has been linked to a range of diseases.

One is a rare genetic disorder called immunodeficiency, centromere instability and facial anomalies (ICF) syndrome, whose symptoms include recurrent respiratory infections, facial abnormalities, and poor growth and cognitive function.

Although it was known that mutations in the CDCA7 gene cause ICF syndrome, little was known about the molecular function of this gene.

In a new study, Professor Hironori Funabiki of Rockefeller University and his colleagues have identified unique functional features of CDCA7 that ensure the correct inheritance of DNA methylation.

The researchers discovered that CDCA7 senses hemimethylation in eukaryotes, an important finding because hemimethylation sensing was long thought to be carried out exclusively by a protein called UHRF1.

“This is a really surprising discovery,” said Isabel Wassing, a scientist at Rockefeller University.

“The discovery that CDCA7 also acts as a sensor explains why mutations in it lead to diseases like ICF syndrome and fills a major gap in the field of epigenetics.”

“But it also raised new questions, such as why do cells need two different hemimethylation sensors?”

“We discovered that the CDCA7 gene, known to be the causative gene for ICF syndrome, specifically binds to hemimethylated DNA on nucleosomes and promotes DNA methylation by controlling the ubiquitination of histone H3,” said Atsuya Nishiyama, a research scientist at the University of Tokyo.

Scientists know that chromatin limits access for many enzymes and DNA-binding proteins, including those needed to introduce methylation into DNA.

Previous research by Professor Funabiki’s team has shown that CDCA7 forms a complex with a protein encoded by the HELLS gene, mutations of which also cause ICF syndrome.

HELLS is a so-called nucleosome remodeller that can temporarily release DNA molecules from nucleosomes.

“We reasoned that the CDCA7-HELLS complex is important in helping cells overcome the barrier of condensed heterochromatin and make DNA molecules available for methylation deposition,” Professor Funabiki said.

“But there are many nucleosome remodelers that can expose DNA molecules in this way.”

“It remained a mystery to us why CDCA7-HELLS is the only nucleosome-remodeling complex directly linked to DNA methylation maintenance.”

“By showing that CDCA7 specifically recruits HELLS to hemimethylated DNA, we finally have an explanation.”

In this model, CDCA7 recognizes hemimethylated DNA in chromatin and recruits HELLS to the site, which acts as a nucleosome remodeler to slide nucleosomes and reveal the hemimethylated site to UHRF1.

The takeover of hemimethylation sensing indicates that CDCA7 is better at detecting hemimethylation in dense heterochromatin than UHRF1 and also explains why cells require two distinct sensors.

“For these sensors to detect hemimethylation, they need to bind directly and selectively to hemimethylated DNA substrates,” Dr. Wassing said.

“CDCA7 appears to perform its function independently while DNA is wrapped around the nucleosome. Without CDCA7, UHRF1 cannot recognize the hemimethylation signals within the nucleosome particle.”

“Our findings suggest that CDCA7 and HELLS promote DNA methylation through a mechanism distinct from de novo DNA methylation, and this is strengthened by our demonstration that the CDCA7 HMZF domain specifically recognizes hemimethylated CpGs, which are substrates for the maintenance DNA methyltransferase DNMT1,” said Dr. Nishiyama.

“ICF disease-associated mutations in the CDCA7 gene abolish hemimethylated DNA binding, supporting the functional importance of hemimethylation detection by CDCA7.”

This new understanding may help elucidate the underlying mechanisms of diseases resulting from methylation dysfunction.

In the future, the functions of hemimethylation sensors beyond maintaining DNA methylation will be explored.

“Because some chromosomal regions are known to maintain a hemimethylated state, their recognition by CDCA7 may play a broader role in gene regulation and chromosomal organization, which is a very intriguing possibility,” says Professor Funabiki.

“Our research lays the foundation for the development of new DNA methylation inhibitors and therapeutic drugs for ICF syndrome,” said Dr. Nishiyama.

“Therapies that artificially control CDCA7-dependent DNA methylation may be useful for preventing cancer and aging and extending healthy lifespan.”

of Survey results Featured in this month’s journal Scientific advances.

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Isabel E. Wassing others2024. CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes. Scientific advances 10 (34); doi: 10.1126/sciadv.adp5753

This article is based on a press release from Rockefeller University.

Source: www.sci.news

Evidence of Indigenous Canines in Jamestown Colony during the 17th Century Unearthed through Ancient DNA Analysis

Posted on August 21, 2024 by Igor Mitreski

Multiple studies have demonstrated that European colonization of the Americas caused the extinction of most mitochondrial lineages of North American dogs between 1492 and present, and that they were replaced by European lineages. Historical records indicate that colonists imported dogs from Europe to North America, and that they became objects of interest and exchange as early as the 17th century. However, it is unclear whether the oldest archaeological dogs found from the colonial period were of European, Native American, or mixed ancestry. To determine the ancestry of dogs from the Jamestown Colony in Virginia, scientists sequenced ancient mitochondrial DNA (mtDNA) from six archaeological dogs dating from 1609 to 1617.

Lithograph “Indian Dog with Rabbit” by John Woodhouse Audubon.

Europeans and Native Americans treasured dogs as pets, used them for similar tasks, and as symbols of identity.

As a result, the dogs reflected the tensions between European and Native American cultures: settlers described Native American dogs as mongrels to emphasize their perception that Native Americans would not breed or own dogs.

Indigenous peoples perceived European dogs as a direct threat to their existence and took steps to restrict their use.

“Previous research had suggested that there were many indigenous dog species in the continental United States, but that they had gone extinct,” said Ariane Thomas, an anthropologist at the University of Iowa.

“We wanted to understand what it meant: when did it happen, were the dogs culled, were they in competition with European dogs or were they sick?”

Dr. Thomas and his colleagues focused on the Jamestown Colony in Virginia because of the number of dog remains found at the site and evidence of Native American influence.

They were able to identify and analyze 181 bones representing at least 16 different dogs.

Of these, the researchers selected 22 sites that span multiple points in Jamestown's early settlement, from 1607 to 1619.

To better understand the ancestry of these dogs, they extracted and sequenced ancient mtDNA.

Based on body size estimates alone, the researchers found that most of the Jamestown dogs weighed between 10 and 18 kg (22 and 39 pounds), comparable to modern beagles and schnauzers.

Additionally, many of the dog bones bore signs of human damage, including burn marks and cuts.

“Cut marks and other signs of butchery found on the dogs indicate that some of these dogs were eaten,” Dr Thomas said.

“This suggests that when settlers arrived, they did not have enough food and had to rely on the native dogs of the area.”

“Furthermore, DNA sequencing demonstrated that at least six of the dogs showed evidence of Native American ancestry.”

“Our findings indicate that there were indigenous dogs in the region and that they did not quickly become extinct when Europeans arrived.”

“While it is not surprising that dogs could be identified with Native American ancestry, our results suggest that settlers and Native American tribes may have been exchanging dogs and had little concern about potential interbreeding.”

of Survey results Published in the journal American Antiquity.

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Ariane E. Thomas othersTsenacomoco Dogs: Ancient DNA reveals presence of local dogs in Jamestown Colony in the early 17th century. American AntiquityPublished online May 22, 2024, doi: 10.1017/aaq.2024.25

Source: www.sci.news

Freeze-dried jerky with remarkably well-preserved mammoth DNA.

Posted on July 12, 2024 by Igor Mitreski

39,000-year-old mammoth leg

Love Darren/Stockholm University

The woolly mammoth, which died 52,000 years ago, has been so well preserved that it’s now possible to sequence its entire genome and reconstruct the three-dimensional structure of its chromosomes. This information provides unprecedented details about how the animal’s genes moved throughout its life. This incredible feat was made possible because the animal’s remains were naturally freeze-dried, preserving its DNA in a glass-like state.

Scientists discovered the remains of a mammoth preserved in permafrost in a Siberian cave in 2018. The mammoth’s tissue was dry, but “not as dry as commercial beef jerky,” the researchers said. Olga Dudchenko “It was, in fact, hairy,” says a researcher at Baylor College of Medicine in Texas. Wanting to find out what genetic information they could find, Dudchenko and his colleagues took a sample of flesh from behind the mammoth’s ear and sequenced its DNA.

“Until now, scientists have only been able to find small parts of the mammoth’s genome because DNA molecules begin to degrade when an animal dies, but to the researchers’ surprise, the animal’s chromosomes were completely preserved. “This was quite a surprise, as it doesn’t match anything we’ve analyzed so far from 52,000 years ago,” the researchers say. Juan Antonio Rodriguez Members of a research team from the University of Copenhagen in Denmark.

They also found that mammoths had 28 pairs of chromosomes, the same number as their closest living relative, the Asian elephant. The three-dimensional structure of the chromosomes was also preserved, which helps distinguish active from inactive genes. For example, the genes responsible for hair growth in mammoths were more active than in elephants, allowing the researchers to determine why they have such thick fur.

Identifying whether mammoth or elephant genes are more active could aid in so-called de-extinction efforts, he said. Hendrik Poyner “To get as close as possible to a real mammoth, [genetic] “The skeleton of a mammoth is different from that of an Asian elephant,” he says. Understanding which genes to tweak, such as the one that produces lots of hair, could help create a more realistic-looking and sounding animal that, while not a bona fide mammoth, more closely resembles the ancient pachyderm.

But how did this DNA remain intact for more than 50,000 years? The researchers attribute it to the cave’s ideal conditions, which cooled and dried the animal. “The sample lost much of its moisture during the cold, dry Siberian winter,” says Dudchenko. She adds that a similar drying process occurs during the production of foods such as prosciutto.

To test their theory, the researchers put fresh and freeze-dried beef liver through a series of rigorous tests. After three days at room temperature, the fresh beef’s DNA had fragmented; but the freeze-dried version still retained its nanometer-scale chromosome structure after a year. “At that point, we wondered, rather than time killing it, what is killing it?” Dudchenko says.

So the team tried to destroy the DNA of the mammoth jerky replica by shooting it with a shotgun, running it over with a car, and having a former professional baseball player throw a fastball at it. Each time, the dried beef liver crumbled into pieces, but its microscopic structure remained intact, preserving the DNA inside. “We found that this method worked, and that it survived,” Rodriguez says.

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Source: www.newscientist.com

New DNA research reveals insights into the ancient ancestry of Australia’s dingoes

Posted on July 10, 2024 by Igor Mitreski

Dingo (Dingo) are an iconic element of Australia’s biodiversity, but evidence-based management and conservation of dingoes depends on understanding their origins and population history. New ResearchIssued this week Proceedings of the National Academy of SciencesResearchers have sequenced the genome of an ancient dingo individual, providing clues about the early history of dingoes in Australia, prior to the introduction of modern domestic dogs and the persecution of dingoes by European settlers. The results provide insight into the ancestry and origins of modern dingoes, including their relationship to the singing dogs of New Guinea, and will be a valuable resource for future developments in dingo management and conservation.

Dingoes are culturally and ecologically important free-living canines whose ancestors arrived in Australia more than 3,000 years ago, likely carried by sea voyagers. Image courtesy of Karlel.

Modern dingoes are free-ranging and naturalized Canine They live on most of mainland Australia and some of the nearby islands, including K'gari (known as Fraser Island from the 1840s until 2023).

Between the arrival of their ancestors in Australia at least 3,000 years ago and the introduction of domestic dog breeds as part of European colonisation beginning in the 18th century, dingoes were isolated from domestic dogs for thousands of years and represent an early 'primitive dog' lineage distinct from other free-ranging representatives of modern domestic dogs.

The early branching and free-living nature of dingoes means they were not subjected to the same intensive selective breeding as the ancestors of modern domestic dogs.

As a result, dingoes are behaviorally, genetically and anatomically distinct from domestic dogs and, as the continent's largest and most widespread terrestrial predator, they affect the distribution and populations of many other animal species.

“Dingoes have cultural significance to Aboriginal and Torres Strait Islander people and play a vital role in Australia's ecosystems,” said University of Adelaide researcher Dr Yasin Suirmi.

“Understanding the historical population structure of dingoes will help us to protect their role in Australia's ecosystems and culture.”

“Dingoes are currently under threat from lethal culling programs and our research highlights the importance of protecting populations both inside and outside national parks.”

For the study, Dr Suirmi and his colleagues sequenced genetic data from 42 dingo specimens taken from coastal Western Australia, the Nullarbor Plain and coastal eastern Australia, stretching more than 3,000 kilometres from east to west.

The majority of the dingo specimens the researchers analysed predate the arrival of Europeans in Australia, with some dating back more than 2,000 years, and therefore represent the true genetic diversity of dingoes before they interbred with modern domestic dog breeds.

“This dataset provides a rare glimpse into the genetic landscape of pre-colonial dingoes, without any interbreeding with modern dog breeds,” said Dr Sally Wasef, a palaeogeneticist at Queensland University of Technology.

“As a result, they are behaviorally, genetically and anatomically different from domestic dogs.”

“The ancestors of modern dingoes arrived in Australia more than 3,000 years ago, probably carried there by seafarers.”

“The samples we analysed represent the oldest ancient DNA ever found in Australia and point to broad potential for future DNA and conservation action for dingoes and other animals.”

“Dingo populations have been divided into eastern and western groups and were previously thought to have formed during post-colonial human activity.”

“However, our results show that dingo population structure was already present thousands of years ago, shedding light on the dingo's genetic heritage and highlighting the importance of using ancient DNA for wildlife conservation.”

“For example, all of the K'gari dingoes we analysed are free of domestic dog blood, proving they have retained their ancestral heritage intact.”

“Although we only studied a small number of K'gari dingoes, our results highlight the importance and usefulness of ancient pre-colonial genomic data in conserving our unique native fauna.”

“Bad human behaviour has led some dingoes to take food from tourists so although a few problem dingoes have been culled, this is concerning given the small population.”

“Our unique dataset of ancient dingo DNA has helped us to reveal important details about the ancestry and migration patterns of modern dingoes,” Dr Suirmi said.

“Dingoes existed in Australia long before Europeans arrived, with distinct regional populations roughly separated along the Great Dividing Range, and certainly before the construction of the dingo-proof fence.”

“DNA analysis also shows that there has been less interbreeding between dingoes and modern dogs than previously thought, and our study confirms that today's dingoes retain a significant amount of their ancestral genetic diversity.”

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Yasin Suirmi others2024. Ancient genomes reveal dingo population structure over 2,000 years. PNAS 121(30):e2407584121; doi:10.1073/pnas.240758412

Source: www.sci.news

Ancient DNA unravels the evolutionary history of Australian dingoes

Posted on July 9, 2024 by Igor Mitreski

Dingoes are found across most of the Australian continent.

Dominique Jeanmaire/Getty Images/iStockphoto

Analysis of ancient dingo DNA suggests that Australia's native wild dogs arrived in two migration waves between 3,000 and 8,000 years ago, and show little evidence of interbreeding with domestic dogs.

Sally Wasef Researchers from the Queensland University of Technology in Australia looked at 42 ancient dingo specimens, ultimately obtaining nine complete genomes, including the oldest genome of any Australian species sequenced to date, as well as mitochondrial DNA from 16 animals.

The DNA recovered dates from 400 to 2,700 years ago and was collected from across the continent. The researchers compared this ancient data with DNA from 11 modern dingoes, six New Guinea singing dogs, and 372 domestic dogs, wolves, and other canines collected in previous studies.

The analysis confirmed that Australia's two main dingo populations – those concentrated on the east and west coasts – diverged at least 3,000 years ago, and because the east coast dingoes are more closely related to the singing dogs of New Guinea than are the west coast dingoes, it is possible that dingoes migrated to Australia in two waves.

Because no DNA from ancient New Guinea singing dogs was found, the researchers could not rule out the possibility that the singing dogs were descended from dingoes that migrated to New Guinea from Australia.

People have long known that dingoes descended from wolves, but “without ancient DNA we couldn't figure that out,” Wassef said.

Since Europeans arrived in Australia, dingoes have been hunted and killed as a threat to the livestock industry.

In recent years, there have been a number of dingo attacks on humans on K'gari Island, also known as Fraser Island, off the coast of Queensland, leading to the animals being euthanized.

Analysis of ancient DNA found no evidence that the K'gari dingoes interbred with domestic dogs. “It's been suggested that dingoes interbred with domestic dogs to provide an excuse to kill them,” Wassef said. “Our results don't show evidence of widespread interbreeding.”

To protect K'gari dingoes' gene pool, Wassef said the practice of euthanizing dingoes may need to be reconsidered: “K'gari dingoes already suffer from inbreeding and killing individuals would significantly reduce their DNA.”

“This study is exciting because it provides some of the data we need to investigate the evolutionary relationships between dingoes, New Guinea singing dogs, dog populations around the world and wolves,” Kylie Cairns At the University of New South Wales, Sydney.

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Source: www.newscientist.com

Unraveling the Secrets of Dark DNA: Scientists on the Verge of Decoding Your Genome

Posted on June 30, 2024 by Igor Mitreski

Back in the spring of 2003, the Human Genome Project completed the monumental task of sequencing the human genome.

Even now, The Book of Life remains a captivating and complex subject for the world’s top geneticists, as they work to unravel its mysteries.

This achievement was not only a major milestone for science but for life on our planet, marking the first time any organism had documented its fundamental genetic makeup. This event sparked the ongoing genetic revolution but also presented profound questions.

Questions like, “Why is there so much genetic material?”

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One intriguing aspect of the human genome is that the majority of it seems to serve no apparent function. With around 3 billion nucleotide pairs (A, C, G, T), fewer than 2% (approximately 20,000) of these are genes responsible for coding proteins that direct cellular activity in the body. So, what purpose do the remaining genes serve?

Some have referred to these as junk DNA: seemingly meaningless genetic remnants accumulated over the course of evolution or like a convoluted word puzzle with little coherence.

However, ongoing research indicates that at least some of these regions are not simply genetic debris but have crucial regulatory and corrective roles in the human genome’s protein-coding genes. These DNA sequences are likened to the controls for gene expression.

For instance, enhancer sequences boost gene transcription from DNA to RNA, while silencers have the opposite effect.

The dark genome largely consists of lengthy repeat DNA sequences called Transposons, which play vital roles in gene expression, evolutionary processes, and environmental adaptation.

These “jumping genes” can relocate within the genome, potentially causing significant genetic mutations or inversions. Scientists posit that transposons are linked to evolutionary developments such as opposable thumbs in humans and the loss of tails in humans and apes.

In certain scenarios, transposons may contribute to the onset of tumors and genetic disorders like hemophilia and Duchenne muscular dystrophy, stemming from repetitive DNA sequences associated with transposons.

As a result, the dark genome has become a focal point of medical research, with hopes that increased understanding over the next two decades will lead to revolutionary therapies for genetic diseases.

This content addresses the query of “What makes up the other 98% of DNA?” posed by Asa Mcintyre via email.

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Source: www.sciencefocus.com

‘Refining Bridge Editing: A Potential Improvement Over CRISPR for DNA Modification’

Posted on June 26, 2024 by Igor Mitreski

Bridge editing physically links two DNA strands

Visual Science

A powerful DNA-editing mechanism discovered in bacteria has the potential to enable much larger genome modifications than are currently possible with CRISPR-based techniques, but it is not yet clear whether it would work in human cells.

Patrick Shue Researchers at the Ark Institute in California call their new genome editing system the “bridge editing” system because it physically links, or bridges, two strands of DNA. “Using this system, we can modify large parts of the genome,” says Su. Su's team has figured out how bacterial “parasitic” DNA sequences naturally replicate using this system and how it can be applied to genome editing.

“We're excited about the possibility of making much broader genome modifications that go far beyond what we can do today with CRISPR,” he says, “and we see this as an important step toward a broader vision for genome design.”

CRISPR gene editing has revolutionized biology since it was introduced in 2012. It is used for a variety of purposes, and the first CRISPR-based therapeutic was approved last year. However, the basic form of CRISPR, which uses the Cas9 protein, is gene disruption rather than gene editing.

A standard CRISPR Cas9 protein has two parts: one part binds to a guide RNA molecule and looks for DNA that matches a specific section of the guide RNA. Custom guide RNAs are easy to create, so CRISPR Cas9 can be “programmed” to look for any part of the genome.

The second part of CRISPR Cas9 is a cutter that cuts the DNA when Cas9 binds to the target site. Once the cell has repaired the damage, Cas9 cuts it again. This action continues until an error is made during repair, resulting in the intended mutation of the target site.

While being able to mutate specific sites is useful, biologists want to make more precise changes, so they are modifying CRISPR proteins to edit DNA directly rather than relying on cellular repair mechanisms. For example, base editors can change one DNA letter to another without cutting the DNA, while prime editors can convert an extra section of guide RNA into DNA and add it to the target site.

These improved versions of CRISPR have the potential to treat a wide range of diseases, with several clinical trials already underway, but to address some diseases, more sophisticated genome modifications are needed. Many teams around the world are working on ways to achieve this. Some have realized that the mechanism by which genetic parasites cut and paste from one part of the genome to another, called IS110 elements, has potential because, like CRISPR, it is RNA-guided, but Hsu's team is the first to fully understand how it works.

The bridge-editing system consists of a so-called recombinase protein that binds to a guide RNA, such as the CRISPR Cas9 protein. What's unique about this system is that the guide RNA specifies two DNA sequences to seek out, not just one, Hsu's team found.

One sequence specifies the target site in the genome to modify, similar to CRISPR, and the other specifies the DNA to change. Using this system, DNA sequences of virtually any length can be added, deleted, or inverted.

There are already ways to do this, but they typically require multiple steps and leave behind a piece of extra DNA called a scar. “Bridge editing leaves virtually no scar,” Hsu says. “It offers an unprecedented level of control in engineering the genome.”

This means that it could be used for more than just replacing faulty genes, he says: It could also be useful for completely remaking the genomes of plants and animals. “What we want to do is go from inserting individual genes to doing chromosome-scale genome engineering,” Su says.

“The findings reported are certainly exciting and the underlying biology is truly surprising.” Steven Tang Bridge editing is being done at Columbia University in New York, but so far it has only been demonstrated to work in bacterial cells or in test tubes. Tang says it remains to be seen whether and to what extent bridge editing will work in complex cells like humans. But even if bridge editing doesn't work in initial tests in human cells, it may be possible to modify the system to work over time.

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Source: www.newscientist.com

Cracking the Code: Scientists on the Brink of Revealing the Secrets of Dark DNA

Posted on June 9, 2024 by Igor Mitreski

In the spring of 2003, the Human Genome Project completed the task of sequencing the human genome, marking a significant moment for science and life on Earth. The genetic revolution that followed raised questions about the meaning of the genome, particularly the fact that most of it seems to be non-coding. Less than 2% of the genome consists of genes that code for proteins, while the rest was once considered junk DNA.

However, recent research has shown that this “dark genome” plays a crucial role in regulating gene expression and has evolutionary significance. Long repeat sequences like transposons can impact genetic mutations and adaptation, leading to the development of features like opposable thumbs and the loss of tails in humans and apes. Understanding these once-neglected parts of the genome is now a focus of medical research for potential therapies for genetic diseases.

This article addresses the question of what makes up the other 98% of DNA, shedding light on the hidden functions of the dark genome. If you have further questions or want more information, you can reach out on our Facebook and Instagram pages.

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New DNA studies indicate that modern horses were not domesticated until at least 2700 B.C.

Posted on June 8, 2024 by Igor Mitreski

Horses revolutionized human history by increasing mobility, but the timeline between their domestication and widespread integration as a form of transportation remains debated.

Genetic evidence suggests that modern domestic horses emerged around 3000 BC in the steppes of western Eurasia, including an area inhabited by nomadic peoples known as the Yamnaya.

According to some accounts, the Yamnaya people migrated to Europe on horseback.

The earlier appearance of a different lineage of domesticated horses (probably used for milk) in association with the Botai culture of Central Asia (context: c. 3500 BC) also adds confusion.

To explore the possible timing of domestication, Dr. Ludovic Orlando of the Toulouse Centre for Anthropology and Genomics, Dr. Pablo Librado of the Barcelona Institute of Evolutionary Biology and their colleagues analysed the genomes of 475 ancient horses and 77 modern horses.

“I started working with horses about 10 years ago, and at the time there were only a few ancient genomes,” Dr. Librado said.

“With this new study, we now have hundreds of specimens. The increased resolution over Central Europe, the Carpathians and the Transylvanian Basin was particularly important, as this region was at the heart of the ongoing debate about a large-scale horse-driven migration out of the steppes around 5,000 years ago, or maybe even earlier.”

The researchers found that around 2200 BC there was a clear change in horse breeding practices (including the introduction of inbreeding), which resulted in the replacement of almost all horse bloodlines with modern livestock bloodlines.

This expansion was preceded by a domestication bottleneck (starting around 2,700 BC) that shortened generation times (related to the age at which horses breed) and made it easier to breed new domestic horses.

Previous studies have suggested that the Yamnaya migration occurred between 3,300 and 2,600 BCE.

The timing suggested by this study is therefore inconsistent with the hypothesis that the Yamnaya-related steppe peoples were accompanied by large herds of modern domesticated horses.

The authors also found evidence of domestication of the Botai horse, including shortened generation times, which means that horse domestication may have occurred in some areas before 2700 BC, but did not lead to widespread migration of horses.

“One question I've long wondered about is the scale of production: how was it possible to suddenly keep such large numbers of horses from a relatively small livestock area to meet growing global demand by the turn of the second millennium BC?” Dr Orlando said.

“Now we have the answer: breeders have controlled the reproduction of the animals so well that the time interval between two generations has been almost halved.”

“Simply put, they were able to speed up the breeding process and essentially double their production rate.”

“Our methodology for measuring temporal changes in generation time has great potential,” Dr. Librado explained.

“This adds a new method to the archaeozoological toolkit for monitoring the development of managed breeding in a range of livestock species beyond horses.”

“But it could also help shed light on generation intervals in our hunter-gatherer ancestors and how these intervals evolved alongside changing lifestyles and significant climatic changes.”

“Our evidence supports two stages of domestication of the horse,” Dr Orlando said.

“The first attempts, which occurred around 5,500 years ago, were aimed at addressing the decline of horse populations and providing food for people living on the steppes of Central Asia.”

“The domestic horse as we know it emerged from a second period of domestication about 4,200 years ago.”

“This allowed high-speed travel for the first time and truly changed human history.”

of study Published in this week's journal Nature.

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P. Librado otherHorse travel became widespread in Eurasia around 2200 BC. NaturePublished online June 6, 2024; doi: 10.1038/s41586-024-07597-5

Source: www.sci.news

Is 23andMe’s DNA Trustworthy Without Significant Safeguards? | Data Protection

Posted on February 17, 2024 by Igor Mitreski

WIs hats next for 23andMe? Most people know this biotech company as a genetic testing service. The story of a woman who sends a cheek swab through the mail and discovers that the parents who raised her were not her biological parents has become something of a millennial horror genre. Of course, most 23andMe experiences aren’t that dramatic. The company says more than 14 million people have used the service to learn more about their ancestry.

But this month, 23andMe revealed it was facing major financial troubles, and more information emerged about the company’s devastating security breach last year. Now, customers may be wondering, “Can I trust his DNA on 23andMe?”

DNA “bait and switch”

Last week, 23andMe reported dismal third-quarter results, and the company’s stock price slumped.
CNBC reported. The company’s financial difficulties come down to longevity issues. The company’s most famous service, DNA ancestry testing, is a one-time transaction. After being tested, there is no reason for consumers to continue paying for his 23andMe, and it has reached a kind of plateau.

Nevertheless, the company’s CEO, Ann Wojcicki, said:
wired She remains “optimistic” about 23andMe’s future.

At-home DNA testing is so popular that you can even order one for your dog. 23andMe was the first company to offer this (human) service in 2007, and it now serves an estimated one in five American girlfriends.
I’ve tried Genetic testing that can be done at home. Some customers handed over personal data that Wojcicki and others used for purposes other than family reunions.

From 2018 to 2023, 23andMe partnered with pharmaceutical giant GlaxoSmithKline to use customers’ genetic information to help develop drug targets. (Drug targets are molecules involved in a disease. Researchers use them to develop treatments for specific diseases.) This year, the partnership became non-exclusive. This means 23andMe can sign deals with more drug companies and squeeze more money out of them. From the treasure trove of DNA.

“This is a real resource that different organizations can apply to their own drug discovery,” Wojcicki said, adding that 23andMe is interested in researching inflammatory immunology, particularly asthma.

23andMe already has two cancer drugs in clinical trials. These drugs are created from the user’s genetic data. But 23andMe users may not realize that the spit they gave the company months or years ago is being used to make more money.

As Health Reporter Kristen V. Brown
I have written For Bloomberg in 2021: “It’s strange that the 8.8 million 23andMe customers who once said, sure, use my data for whatever they want and didn’t check the box, now feel like they’ve been baited. Now they’re making the switch because their genes lay the foundation for potential cancer treatments. ” (Since 2021, the number of customers who have checked that box has grown to 10 million, according to Wired.)

Americans tend to believe that their health data is protected by Hipaa, the medical privacy law, and 23andMe, with its official-looking cheek swabs and far-flung labs, sure is too. However, 23andMe is not a healthcare provider.same rules
do not apply.

“There are no significant safeguards or regulations around the collection and sale of truly sensitive personal data,” said Suzanne Bernstein, a legal researcher at the Electronic Privacy Information Center. “A nefarious presence for 23andMe.” [data] A breach constitutes a security issue, but so does a company sharing your information with a third party you don’t know. Customers can technically consent to data sharing by agreeing to terms and conditions, but they are very long and many people don’t read them. ”

Ann Wojcicki, CEO of the company, 2015. Photo: Brad Barket/Getty Images for Fast Company

Some people may feel honored to have their genes used in cancer research. Some people may feel cheated because they paid about $229 for a DNA test kit and 23andMe is using their health data for free. Torin Klosowski, a security and privacy activist at the Electronic Frontier Foundation, said 23andMe could do more to help customers better understand the move before opting in.

“The fact that so many people are surprised by the amount of data being leaked elsewhere is a sign that 23andMe is not explaining things very clearly,” he said.

Klosowski added that users can opt out of 23andMe’s use of their data long after they have shipped their DNA swab, but that information may already have been used for research purposes. “You can ask 23andMe to stop using your information, but you cannot ask 23andMe to remove your sold data from its lists,” he said.

On the other hand, 23andMe
maintain Users are asked to select a survey at the time of purchase and all personal data is de-identified before being shipped for analysis. Your data will not be used without this consent, which you can withdraw. The company’s research department is also overseen by an “independent and impartial” review board. (23andMe did not respond to a request for comment.)

Data breaches lead to class action lawsuits

The 23andMe security breach is still on the minds of many customers. Approximately 7 million customer profiles were hacked last year. Over a five-month period, hackers compromised the personal information of up to 5.5 million people who opted in to one of 23andMe’s best-known features, including their career status reports. I was able to access my health records. Find relatives.

Customers of Chinese and Ashkenazi Jewish descent appear to have been targeted in the breach, and their information was sold on the dark web, the New York Times reported.
report. Some of these users recently filed a class action lawsuit against 23andMe, alleging the company failed to notify them of the exposure.

As The Guardian reported on Thursday, 23andMe in a letter to customers downplayed its responsibility for the hack and made claims about the health information that was accessed. “It cannot be used for the purpose of causing harm. The company also criticized customers for “carelessly recycling their passwords and not updating them,” a response one former customer called “morally and politically foolish.”

Wojcicki did not directly discuss the breach due to pending litigation, but told Wired that 23andMe introduced two-factor authentication and forced customers to reset their passwords. “Data privacy and security has always been a very high priority and continues to be a high priority for the company, and we intend to further invest in it,” she said.

Will 23andMe’s security problems spell the end for a company once hailed as a “corporate” by Time?
inventions of the year? Regardless of whether customer privacy concerns are well-founded, the company’s financial position is rapidly deteriorating, and CNN
report If the stock price does not rise, the company could be delisted from the Nasdaq.

Dominic Sellitto, a clinical assistant professor at the University at Buffalo who specializes in digital privacy, believes that if 23andMe survives this year, it will be thanks to data mining. “There is a lot of demand and funding for data, especially high-quality health data,” he said. “If 23andMe continues to monetize, it will be the golden ticket in 2024.”

Source: www.theguardian.com

The Genetic Origins of Multiple Sclerosis in Northern Europeans Revealed by Ancient DNA

Posted on January 12, 2024 by Igor Mitreski

Northern Europeans have a higher risk of multiple sclerosis due to ancient DNA, a study reveals. About 5,000 years ago, people flocked to this area.

This discovery emerged from a large-scale study comparing modern DNA with DNA obtained from ancient human teeth and bones. This allowed scientists to explore prehistoric migration and associated disease-related genes.

Results show that when the Yamnaya people migrated from present-day Ukraine and Russia to northwestern Europe during the Bronze Age, they carried a genetic mutation. This mutation is now known to increase the risk of multiple sclerosis.

The study, published in the journal Nature, suggests that these genes not only allowed the Yamnaya to flourish and spread but also protected them from infectious diseases carried by cattle and sheep.

The project, led by Eske Willerslev and the University of Copenhagen, is pioneering ancient DNA research and comparing it to similar research, including tracking down early cousins such as Neanderthals.

The process of ancient DNA extraction at the Lundbeck Foundation Geogenetics Center in Copenhagen.Michal Schlosser / University of Copenhagen (via AP)

This gene bank’s first exploration of multiple sclerosis is especially relevant since the disease is most common among people of white Scandinavian descent, yet the reason remains unknown.

Scientists believe certain infections can cause MS in genetically susceptible individuals. Over 230 genetic mutations have been identified that may increase the risk of this disease.

The study uncovered major changes in the population of northern Europe, tracing the migration of the Yamnaya people around 5,000 years ago. The gene bank was used to compare ancient DNA with around 400,000 modern humans

Comparisons revealed that MS-related genetic variants remained in the north, the direction the Yamnaya migrated, rather than in southern Europe. This supports the idea that the Yamnaya people are the closest ancestors of modern Danes, and the incidence of MS is particularly high in Scandinavian countries.

Dr. Astrid Iversen from the University of Oxford explains how exposure to animal-based bacteria may lead to imbalances in the immune system, possibly playing a role in the early development of autoimmune diseases.

While the study provides a potential explanation for the North-South MS disparity in Europe, further research is required to confirm the link. This statement comes from New York’s M.D., Samira Asghari, a genetics expert at Sinai School of Medicine, who was not involved in the study.

Source: www.nbcnews.com

The influence of ancient Neanderthal DNA on modern daily routines

Posted on December 26, 2023 by Igor Mitreski

Recent research has revealed a link between Neanderthal genetics and the tendency of some modern humans to wake up early. The study traces back to the interbreeding of modern humans and Neanderthals in Eurasia and suggests that genetic variation in Neanderthals influences the circadian rhythms of modern human descendants. Credit: SciTechDaily.com

A new paper has been published in a magazine Genome biology and evolutionAccording to a paper published by Oxford University Press, genetic material from Neanderthal ancestors may have contributed to the tendency of some people today to be “early risers” – the type of people who find it easier to get up early and go to bed. I discovered that there is a possibility that

Human evolution and genetic adaptation

All anatomically modern humans trace their origins to Africa about 300,000 years ago, where environmental factors shaped many of their biological characteristics. About 70,000 years ago, the ancestors of modern Eurasian humans began migrating into Eurasia, where they encountered a variety of new environments, including high latitude regions with large seasonal fluctuations in sunlight and temperature.

But other hominins, such as Neanderthals and Denisovans, lived in Eurasia for more than 400,000 years. These archaic humans diverged from modern humans about 700,000 years ago, and as a result, our ancestors and archaic humans evolved under different environmental conditions. This led to the accumulation of strain-specific genetic variation and phenotypes. When humans came to Eurasia, they interbred with archaic humans from the continent. This created the possibility for humans to acquire genetic variations already adapted to these new environments.

Genes of ancient humans and characteristics of modern humans

Although previous studies have shown that many of the archaic ancestors of modern humans are not beneficial and have been removed by natural selection, some archaic hominin variants that remain in human populations has shown evidence of adaptation. For example, archaic genetic variation is thought to be associated with differences in hemoglobin levels, immune resistance to new pathogens, levels of skin pigmentation, and fat composition among Tibetans at high altitudes.

Changes in patterns and levels of light exposure have biological and behavioral effects that lead to evolutionary adaptations. Scientists have extensively studied the evolution of circadian adaptations in insects, plants, and fish, but humans have been less well studied. The Eurasian environment where Neanderthals and Denisovans lived for hundreds of thousands of years is located at higher latitudes and has more variable daylight hours than where modern humans evolved before leaving Africa. So the researchers investigated whether there was genetic evidence for differences in circadian clocks between Neanderthals and modern humans.

Research methods and findings

The researchers defined a set of 246 circadian genes using a combination of literature searches and expert knowledge. They found hundreds of genetic variations unique to each strain that can affect genes involved in the circadian clock. Using artificial intelligence techniques, they identified 28 circadian genes that contain mutations that could alter splicing in archaic humans and that may be differentially regulated between modern and archaic humans. identified 16 circadian genes.

This indicates that there may be functional differences between the circadian clocks of ancient and modern humans. Eurasian modern humans and Neanderthal ancestors interbred, so some humans may have acquired circadian variation from Neanderthals.

To test this, the researchers studied a large population of hundreds of thousands of people in the UK Biobank and found that introgressed genetic mutations (mutations that passed from Neanderthals to modern humans) could affect wakefulness and sleep. We investigated whether there is a relationship with physical preference for. They discovered a number of introgressed mutants that affected sleep preferences, and most surprisingly, they found that these mutants consistently increased morningness, or the tendency to rise early. This suggests a directional influence on this trait and is consistent with adaptations to high latitudes observed in other animals.

Increased morning time in humans is associated with a shortened circadian clock period. This may be beneficial at high latitudes, as it has been shown that sleep and wakefulness can be coordinated more quickly with external timing cues. Shortening of the circadian period is required to synchronize with the long summer light period at high latitudes in Drosophila, and selection for a shorter circadian period results in the latitudinal period decreasing with increasing latitude in natural Drosophila populations. There is a latitudinal gradient in which the

Therefore, the bias toward morningness in introgressed mutants may indicate selection for shortened circadian periods in populations living at high latitudes. The tendency to be a morning person may have been evolutionarily beneficial to our ancestors who lived in the high latitudes of Europe, and would have been a Neanderthal genetic trait worth preserving.

“By combining ancient times, DNA“After extensive genetic and artificial intelligence research in modern humans, we discovered substantial genetic differences in the circadian systems of Neanderthals and modern humans,” said John, lead author of the paper.・A. Capra said.

“And by analyzing Neanderthal DNA fragments that remain in the genomes of modern humans, we discovered surprising trends, many of which affect the regulation of circadian genes in modern humans. These effects are primarily in the consistent direction of increasing Neanderthal tendencies.” Morning people. This change is consistent with the effects of living at high latitudes on animals’ circadian clocks, which may allow them to adjust more quickly to changing seasonal light patterns.

“Our next steps include applying these analyzes to more diverse modern human populations and investigating the effects of the Neanderthal variants we identified on circadian clocks in model systems. and applying similar analyzes to other potentially adaptive traits.”

Reference: “Archaic Introgression Shaped Human Circadian Traits” by Keila Velazquez-Arcelay, Laura L Colbran, Evonne McArthur, Colin M Brand, David C Rinker, Justin K Siemann, Douglas G McMahon, John A Capra, December 14, 2023 , Genome biology and evolution.
DOI: 10.1093/gbe/evad203

Source: scitechdaily.com

Utilizing DNA from Polar Bear Snow Tracks to Support Conservation efforts

Posted on December 16, 2023 by Igor Mitreski

Researchers have developed a breakthrough method to protect polar bears by analyzing DNA from footprints in the snow. This non-invasive technique can also be applied to other snow-dwelling animals such as lynx and snow leopards, providing a safer and more efficient way to collect data essential to wildlife conservation.

Scientists have discovered a way to capture DNA Observations from snow tracks – a promising non-invasive way to monitor elusive animals like polar bears.

The polar bear is a symbol of the Arctic, an elusive and vulnerable animal. Close monitoring of polar bear populations is critical to polar bear conservation, but polar bears are so difficult to find that critical data about population size and connectivity between those populations is lacking. I am. Scientists have now developed a helpful new tool: DNA analysis using skin cells shed from bear tracks in the snow.

Dr Melanie Lancaster of the World Wildlife Fund’s Global Arctic Program said: ‘Finding polar bears in the Arctic, let alone counting them and understanding how they are coping with climate change, is particularly difficult. “And it’s expensive and time-consuming.” , senior author of the study Frontiers of conservation science.

Innovative forensic techniques in preservation

The scientists were inspired by forensic techniques that can be applied to trace amounts of degraded DNA samples. These techniques eliminate the need to physically capture bears, which can be stressful and dangerous for both bears and humans, and is a concern for some local indigenous communities. Instead, scientists can look at the source of accidentally released DNA: environmental DNA.

A polar bear in Utchagvik, Alaska.Credit: Elizabeth Kruger, World Wildlife Fund

“Many Inuit have expressed concerns about invasive research methods,” said the article’s author, Elizabeth Krueger of the World Wildlife Fund. “People are concerned about the welfare of individual polar bears and the health and safety of those who may later harvest the bears. This is one reason we are so excited about new methods like this. The person collecting the samples does not need to see or even be seen by the polar bear.”

Environmental DNA: a non-invasive tool

A common form of environmental DNA is deposited when animals defecate. However, the quality of DNA is not always sufficient for the individual-level analysis required for preservation. Furthermore, in the case of territorial animals like her other two, seed Scientists tested lynx and snow leopards, and the collection of faeces can affect the animals’ behavior. So the researchers focused on the skin cells in snowy footprints.

“Trucks typically contain fresh cells and the DNA is intact due to the cold ‘storage’ temperatures. “The DNA that passes through the intestine is further degraded, making it more difficult to study,” said lead author Dr Michaela Helström from MIX Research Sweden AB.

Real-world tracking and sampling

The researchers collected snow from individual footprints made by polar bears in Alaska and Eurasian lynx in Sweden in the wild and in captivity. They also collected snow from footprints made by captive snow leopards. Additional substances such as hair, saliva, and mucus were also sampled to ensure that the traces yielded accurate genotypes.

Twenty-four wild polar bear tracks and 44 wild lynx tracks were sampled. The researchers melted and filtered the snow to collect environmental DNA and analyzed the microsatellites. Although the concentration of DNA recovered from footprints collected in the wild was very low, we were able to recover nuclear DNA from 87.5% of wild polar bear footprints and 59.1% of wild lynx footprints. We were able to genotype 13 of the wild polar bear samples and identify 12 different individuals.

They were able to genotype 11% of the lynx footprints, but this percentage increased significantly when scientists examined only footprints sampled by trained personnel. They were able to recover nuclear DNA from 76% of the samples collected by trained personnel and genotype 24% of the samples.

A step-by-step approach

This technology has great potential to inform conservation of these animals, better understand animal populations and behavior, and manage conflicts with humans through accurate animal identification. Although non-invasive sampling has a low success rate, it is easy to collect and can greatly expand sample size.

“We hope this method will be adopted by the polar bear research community as a new way to collect information about polar bears, with the participation of hunters, volunteers, and indigenous communities,” Lancaster said. “We also hope that this method can be extended to other animals that live in snowy environments. We have started by showing that this method works for lynx and snow leopards as well. I did.”

Reference: “Capturing environmental DNA from snow tracks of polar bears, lynx, and snow leopards for individual identification” Michaela Hellström, Elisabeth Kruger, Johan Neslund, Mia Bister, Anna Edlund, Patrick Hernvall, Viktor・Birgerson, Rafael Augusto, Melanie L. Lancaster, October 11, 2023. Frontiers of conservation science.
DOI: 10.3389/fcosc.2023.1250996

Source: scitechdaily.com

“Study suggests Neanderthal DNA might be linked to being a morning person” – UK Researchers

Posted on December 16, 2023 by Igor Mitreski

Have you ever wondered why your partner stays awake with a lark while you doze happily until noon?

According to new research, it could be thanks to Neanderthal genes.

The origins of modern humans can be traced back to Africa 300,000 years ago, but as these ancestors migrated north, they interbred with Neanderthals, and traces of their DNA can still be seen in people today. .

The study’s lead author, John Capra, an epidemiologist at the University of California, San Francisco, said scientists who compared ancient DNA to modern human genetics found “remarkable trends.”

They found that many of the remaining Neanderthal genes influence our body clocks and “increase our tendency to be morning people.”

Neanderthals lived at higher latitudes and farther from the equator than our African ancestors, experiencing longer days in the summer and shorter days in the winter.

Genes that make people wake up earlier “are likely able to adjust their circadian clocks more quickly to changing seasonal light patterns,” Dr. Capra said, which is why Neanderthals maximized daylight hours for hunting. He was able to utilize it to a limited extent.

Scientists have previously investigated how the circadian rhythms of insects, plants and fish have evolved with latitude. However, it has not been well studied in humans.

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Researchers wanted to see if there was a genetic reason for the differences in circadian rhythms between Neanderthals and modern humans, and found 16 mutations associated with greater “morningness”, or the tendency to rise early. .

They reasoned that because Neanderthals interbred with the ancestors of modern humans, modern humans may have inherited Neanderthal “circadian mutations.”

To test this, scientists analyzed the genes of hundreds of thousands of people in the UK Biobank and discovered a number of mutations that affect sleep preferences.

“Most surprisingly, we found that these mutants consistently increased morningness,” the researchers said.

This is consistent with what has been found in other animals that adapted to life at high latitudes, such as Neanderthals.

The study was published in Genome Biology and Evolution.

Source: news.sky.com

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