Which ancient humans can be seen in our DNA? Our ancestors had sex with ancient humans including Neanderthals; But researchers have found DNA traces of previously unknown species in our genome.

Which ancient humans can be seen in our DNA?

In 2010, when the Neanderthal genome was first sequenced and compared to that of modern humans, scientists discovered that Neanderthal genes are also present in our DNA. The conclusion was very simple: our ancestors had intercourse with other humans who are now extinct, and now the genes of these humans remain in us.

In 2012, when Denisova’s human genome was also sequenced, it revealed another example of interspecies mating. Now we know that small populations of all three human families have interbred at different times; Thus, the DNA of our modern humans (homosapiens) today has something in common with groups of ancient hominids that once lived next to us; But they could not survive until today. However, the genes of Neanderthals and Denisovans have not remained in the DNA of all humans. For example, Africans have none of these genes; While Europeans have the genes of Neanderthals. However, these genetic echoes are not clear enough for scientists.

A copy of a finger bone fragment from a Denisovan in the Museum of the History of Science in Brussels, Belgium. This bone was discovered in 2008 in Denisova Cave, Siberia.

Neanderthals and Denisovans were the closest extinct relatives of our modern humans, who diverged more than 390,000 years ago. The Denisovans left Africa before the ancestors of modern humans and spread across the planet, living in Asia around 30,000 to 50,000 years ago. Recent findings show that all human populations outside of Africa have 1-2% Neanderthal DNA, and the DNA of Australian and Melanesian aborigines has 5% Denisovan DNA.
The presence of DNA from other human groups in us modern humans is not so surprising; Because today’s Homo sapiens are the result of millions of years of evolution. We can name several species of ancient anthropoids as our ancestors, But the participation of Neanderthals and Denisovans in our genetic makeup has just happened; That is, after homosapiens separated from other human groups.

These interbreedings, which are called introgression, did not create a new human species; Rather, it has only led to the enrichment of some traits that already existed. We still feel the presence of some of the traits that we have acquired in this way in our lives today.

Adam Seipel, a computational biologist at Cold Spring Harbor Laboratory (CSHL), says:

There is a lot of evidence of interspecies interbreeding between ancient humans and modern humans, especially modern humans outside of Africa; Therefore, there is no doubt about this. Some evidence shows that there may be genes from more than two other anthropoids in our DNA, which some researchers sometimes refer to as ghost lineages. Modern humans living in Africa probably interbred with several ancient human species, adding more genes to our current DNA.
A recent study on the people of Indonesia showed that what we call the Denisovans were actually three separate groups of anthropoids, each of which could be called a separate species. It goes without saying that the ancestors of Asians and Melanesians interbred with at least one of these groups and probably more.

Dark Ghost Hunt

Scientists try to reveal the complex past of us humans in various ways. Such a task would have been easier for species such as Neanderthals and Denisovans, whose DNA is still preserved in fossils. After sequencing the genomes of these ancient humans, archaeologists compared their genomes with those of us today. The great similarity of our DNA to some ancient species is proof that our ancestors had intercourse with these hominids.

However, these genes can originate from a more distant past; For example, maybe from the last common ancestors we had with Neanderthals and Denisovans. However, this split happened a long time ago; So most of the DNA regions we share with other human groups have experienced mutations that have caused the separation of these traits from each other in each group of humans. However, each of these genes is a strong indicator of inter-racial admixture.

According to researchers’ modeling, about 2% of the African genomes that were sequenced originated from an unknown ancient human or the “dark ghost”.

With all this, we should know that scientists have bones or rather fossils for most of the ancient species that we know now, and it is rare that they can find evidence of the DNA of these ancient humans. The problem is that the molecules that make up the nucleic acid helices have been destroyed over time, especially in hot and humid environments; Environments where most of our ancestors lived. However, archaeologists have tried to fill this void of ancient human DNA through statistical modeling. Several studies have also shown that these mysterious ancestors were hidden in our genome; However, the error rate is also high in such simulated models.

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Several studies have shown that mysterious ancestors were hidden in our genome

The mathematical models used by scientists to find ghost families in genetic data are complex, But they are often enough to search for gene clusters in specific human groups today. Recently, a group of researchers did such work and examined a set of 161 genomes of the present-day residents of Indonesia. The researchers compared this genetic information with the genomes of Denisovans, Neanderthals, and other modern humans.

Neanderthal skull that was discovered in 1908 in the ancient cemetery of Lachapel-Assins in France.

Researchers found signs of Denisovan DNA in Indonesian residents, which was not surprising; But the researchers found that these ancient humans were actually three separate groups. These three groups had common ancestors; But when they were scattered in different parts of Asia and the Pacific Ocean, they started to separate from each other. The group whose evidence was found in Siberia was as different from another group as a Denisovan is from a Neanderthal. For this reason, even some researchers declared that this group can be considered a separate species; But fossils of this group have not yet been found to officially prove this assumption.

Murray Cox, a population geneticist from Massey University in New Zealand and lead author of the study, said:

All in all, this new genus of Denisovans is so different from the Denisovans found in Denisovan Cave that if we are going to give different names to Neanderthals and Denisovans, this new group probably needs a new name as well. Therefore, the new findings may give us concrete evidence of this Denisova cousin; But for now, the only clue is a fragment of DNA that remains within the genome of some of us modern humans.
However, these ghostly Denisovans are not alone. Other researchers are also studying the DNA of African hunter-gatherer tribes to find evidence of our ancestors mixing with these tribes tens of thousands of years ago. Perhaps the biggest study of this kind is the research whose results were announced in 2011, in which researchers examined the DNA of 61 Africans from the Mandanka, Biaka, and San tribes. They compared these genomes with two human population models, one of which showed that African ancestors had interbred with human groups; But other comparisons did not show this. This model, which consisted of gene migration (Gene Migration) of ancient humans, obtained results that were more consistent with the real population of the inhabitants of the region.
The researchers announced that based on this modeling, about 2% of the African genomes they sequenced originated from an unknown ancient human. These two groups intermarried about 35 thousand years ago. In another study, researchers evaluated a gene called MUCL7. This gene secretes a protein in our saliva that keeps the mouth moist during chewing, talking, and swallowing and kills some harmful bacteria.

Thus, the researchers were able to find more evidence of the ghost race in Africa. The MUCL7 gene exists in humans today in several variants, and researchers say that it can be attributed to one of the unknown ancient ancestors of humans. Also, in a study in which the genomes of 15 people from the Hadza, Sandui, Baka, Bakula, and Bizen tribes in Africa were examined, evidence of interspecies intercourse was discovered. However, the researchers could not identify the target species.

The Heritage of Modern Humans

The genes that many of us inherited from other human species are still active in our bodies today. The genes of Neanderthals and Denisovans already affect the functioning of our immune system. It is thought that Neanderthal genes affect the body’s keratin, which makes up our hair and nails, and the way the body reacts to UV rays. We modern humans probably got these genes after migrating from Africa to Europe; Where interbreeding with our cousins, the Neanderthals, may have helped us quickly adapt to colder climates.

The entrance to the Denisova Cave in the Altai Mountains of Russia. The first remains of Denisovans and the bones of Neanderthals and modern humans were also discovered in this cave.

This issue is even more surprising in the sense that other populations adapted to life at high altitudes, including the natives of the Andes Mountains in South America and the highlands of Ethiopia in Africa, have achieved such adaptations by increasing hemoglobin. In fact, this adaptation has been done in a different way in Tibetan people. Instead of increasing the number of hemoglobin, Tibetans’ bodies have acquired other adaptations that allow them to use oxygen effectively. This adaptation to a relatively low hemoglobin count at high altitude has prevented the occurrence of the negative aspects of a high hemoglobin count. A high concentration of hemoglobin and as a result thickening of the blood increases the possibility of blood clotting, which, as a result, increases the risk of heart disease and stroke in a person.

There was much more diversity among ancient humans than we previously thought

However, other genetic factors have caused problems. Some Neanderthal genes have been implicated in the occurrence of depression, heart attack, and allergies. While some genes left over from ancient species helped our immune systems, others may have predisposed us, modern humans, to diseases such as systemic lupus erythematosus (an autoimmune disease), Crohn’s disease (an inflammatory bowel disease), and type 2 diabetes.

As with most family inheritances, further understanding of the genetic inheritance of Homo sapiens is more complex. Scientists need to do more research before they can understand the true implications of our multispecies past. In fact, even finding evidence of these ghostly clans can be problematic.

Distinguishing a ghost from an illusion

The dark evidence of the ghost is gradually forming; But when scientists rely solely on genetic evidence, it is clear that they will not be able to prove the existence of a species. There are several factors that can make what we have learned from the remaining genes of ancient humans look completely wrong. For example, what kind of evolutionary pressure the population is under, and things like genetic bottlenecks (an event where only a fraction of the population survives to reproduce) add to the skepticism about purely genetic studies. Thus, what sometimes appears to be a ghost may be nothing more than a curtain flapping in the wind!

A recently published research has clarified some of the shortcomings of this method. In this study, three researchers from Spain and Estonia announced that based on complex statistical analyses and machine learning algorithms, they found evidence of the ghost race in the DNA of Asian and Pacific people.

These researchers first simulated the artificial genome using a computer program and then compared it with population models of ancient humans. Oscar Lau, one of the team’s researchers and a population geneticist at the Center for Genome Regulation in Barcelona, says he and his colleagues ran these simulations millions of times. The researchers then looked at the evolutionary history of the artificial genome to find out what in this genome led to the formation of the gene cluster. On average, the results of more than a million simulations provided scientists with a model they called the equivalent of “a real genome.”

A man loads ice cubes into a truck in Yakutsk, Russia. Interbreeding with Neanderthals may have helped us adapt quickly to cold climates.

This information finally provided researchers with several different modes of interaction between different races of ancient humans. One of the best simulations, they said, was a model of a previously unknown ancient race that had interbred with modern humans. The researchers said that these humans were probably a hybrid race of Neanderthals and Denisovans. Also, this modeling could explain why present-day Asians have inherited more Neanderthal DNA than Europeans. In fact, according to the researchers, the ancestors of Asians have had intercourse not only with Neanderthals but also with another hybrid race. Lao said in this regard that this research once again shows us that human beings are different species and families. He added:

Our findings show that there is a lot of complexity in the genetic diversity of ancient anthropoids. Not only did Neanderthals interbreed with early modern humans; Rather, but other ancient humans have also interacted with modern humans, of which no evidence remains.

While this narrative is interesting in many ways and clearly supports the findings of hybrid humans that were discovered last year in Denisova Cave in Siberia; other researchers are not so convinced. Last August, researchers published the results of their investigations on the bone fragment. Their findings showed that what they had examined was actually the remains of an ancient female hybrid of a Neanderthal mother and a Denisovan father. Earlier in 2012, Russian archaeologists discovered this bone. In their analysis, the researchers found that this bone belongs to a 13-year-old girl who died almost 90,000 years ago. The Denisovan species itself had been discovered two years earlier in 2011 from unusual hominin DNA found in bones found in the Denisovan Cave in the Altai Mountains of Russia in Siberia.

These findings of his are at least generally consistent with the assumption that the Denisovans were more than a species. If so, Cox and Browning may have found evidence of the same specter that was distantly related to the Denisovans, or they may have each found different groups, making it clear that there was far more diversity among ancient humans than previously thought. We used to do it, there has been.

Future research

While scientists claim to have discovered evidence of previously unknown species that had something in common with us in the past, it is reasonable to ask how much such evidence we might find in the future, and what evidence of ghost races we have so far that could support their existence. ? In fact, we may have already passed the range of observable DNA from our ancestors. The DNA of Neanderthals and Denisovans make up only a fraction of the genomes of today’s modern populations. Any extrapolation present could be a small part of our DNA, Browning says. He continues to add that most of the DNA parts that seem to have come to us from other species have probably been found; therefore, there is not much left to work on.

Future archaeological findings can surprise us by providing definitive and reliable evidence; Especially to be able to extract the DNA of the discovered remains. For example, the evidence of Denisovan DNA in our genomes is likely to be too minute to sequence, Seipel says.

He says:

I’m sure if we just try to prove the existence of this species by assuming the existence of minor outbreeding in modern humans, we will enter into a very controversial discussion.
Future findings may turn today’s ghost races into tangible species that were once living, breathing humans; Humans who have left their genetic history in us. Their bodies may be gone, But their DNA is alive.

In a new project, Harvard University researchers investigated an experimental method on mice that might be able to reverse the aging process.

Harvard Medical School (HMS) scientists have investigated the cause of aging and identified a possible way to reverse it. In experiments on mice, they showed that problems in epigenetics trigger the signs of aging and that a reboot can reverse them and perhaps extend life.

Our genome contains a complete map of the DNA found in every cell in our body. This is not the whole picture but an additional layer of information called the epigenome, which controls which genes are turned on and off in different cell types. It’s as if all the cells in our body work based on an operating manual, the genome, but the epigenome is like a list of contents that directs different cells to different chapters, which are genes. After all, lung cells need very further instructions from heart cells.

Reverse aging process

Environmental and lifestyle factors such as diet, exercise, and even childhood experiences can alter epigenetic expression. Epigenetic changes have been linked to the rate of biological aging, but whether they represent signs of aging or are themselves a symptom was not yet clear. Researchers in this project conducted experiments on mice to find out the answer. Using a system called ‘Induced Changes in the Epigenome’ (ICE), they sped up the natural process of DNA damage and repair in mice to see if this accelerated the signs of aging.

In mammalian cells, chromosomes undergo a million DNA breaks per minute, and epigenetic factors rapidly coordinate the repairs before returning to their original sites. The research group engineered mice that underwent DNA breakage at a rate three times faster than usual.

Over time, researchers discovered that epigenetic factors become increasingly disturbed and do not return home after repairing DNA breaks. This leads to epigenome scrambling. At six months, the mice showed physical signs of aging and appeared in significantly worse health than age-matched unedited mice.

Researchers say that this research has confirmed the role of the epigenome in aging. The next step was to test whether something could be done about the problem. Researchers tested a gene therapy combination of three genes named “Oct4”, “Sox2,” and “Klf4”. These genes are active in stem cells, and the researchers found in their previous study that they could be used to restore vision to mice with age-related glaucoma.

New experiments on reverse aging

In this case, the ICE mice experienced a dramatic reduction in biomarkers of aging. Their epigenome was ripped apart, restoring their tissues and organs to a youthful state. David Sinclair, the project’s lead researcher, said: “It’s like restarting a broken computer, and it sets off an epigenetic program that directs the cells to restore the epigenetic information they had when they were young.” This is a permanent reset.

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Researchers believe that this discovery is enormous. Many diseases caused by this natural process can be treated more effectively by tackling aging. Sinclair wrote in a tweet: “If the result is correct, it means that cancer, diabetes, and Alzheimer’s may have the same underlying cause.” In this way, the cause can be reversed to treat age-related diseases.

Although there is still much research to be done before such lofty goals can be realized, research is being done. A preprint paper, which has not yet been reviewed, applied the same gene therapy combination to aged mice, which are the equivalent of 77 years in humans. These mice lived 9% longer than untreated mice.

Via : New atlas

Scientists have discovered a way to create eye tissue using stem cells and 3D printing, which may lead to breakthroughs in the treatment of a wide range of degenerative eye diseases.

Scientists at the National Institute of Vision (NEI) have 3D printed a group of cells that can form the outer blood barrier of the retina. The outer retinal blood barrier is an eye tissue that supports the photoreceptor cells.

Creating eye tissue using stem cells

The method presented by this research group theoretically provides an unlimited source of patient-derived tissue to study retinal degenerative diseases such as macular degeneration (AMD) and use them to better understand how to treat these diseases.

Dr. Kapil Bharti, director of the stem cell and eye research at the National Institute of Vision, said: We know that macular degeneration begins in the outer blood barrier of the retina. Despite this, the mechanisms of initiation and progression of macular degeneration are still poorly understood due to the lack of physiologically relevant human models.

Nearly 20 million Americans suffer from some form of age-related macular degeneration. It is the leading cause of vision loss in Americans age 60 and older and the leading cause of irreversible blindness and vision loss worldwide.

Marc Ferrer, director of the 3D Tissue Bioprinting Laboratory at the National Institute of Vision, said: Our joint efforts have led to the presentation of retinal tissue models that are highly relevant to degenerative eye diseases. Such tissue models have many potential applications in therapeutic development.

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Bharti and colleagues combined three types of immature choroidal cells into a hydrogel. These three types of cells are pericytes and endothelial cells, which are the main components of capillaries, and fibroblasts, which form the structure of tissues. They then printed the gel onto a biodegradable framework, and within days, the cells began to mature and transform into a dense capillary network.

On day 9, the scientists’ cultured retinal pigment epithelial cells on the other side of the biodegradable framework. Just one month later, the tissue reached full maturity. During subsequent experiments, the scientists found that the printed tissue resembled the outer blood barrier and retina of the real eye.

“By printing the cells, we facilitate the exchange of cellular signals that are essential for the normal anatomy of the blood-outer retinal barrier,” Bharti explained.

Via : NIH