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NEANDERTHALS, DNA AND HUMANS
A study in Science on DNA from both Neanderthal and Homo sapiens indicated that the genomes for both groups are greater than 99.5 percent identical. Other studies have shown non-Africans today carry 1 to 6 percent of Neanderthal DNA. As of July 2017, number of Neanderthals from whom we have genetic information was 18.
According to DNA taken from a 50,000-year-old a fossilized Neanderthal toe bone found in a Siberian Cave: 2 percent of the DNA of modern people not of African descent came from Neanderthals and 0.5 percent of Denisovan DNA came from Neanderthals, and that an estimated 0.2 percent of the DNA of mainland Asians and Native Americans comes from Denisovans. [Source: Monte Morin, Los Angeles Times, December 18, 2013 \=]
Chris Stringer wrote in The Guardian: “Recent massive improvements in recovery and analysis of ancient DNA have produced even more information, some of it very surprising. Fossil fragments from Croatia have yielded up a nearly entire Neanderthal genome, providing rich data that promise insights into their biology – from eye colour and hair type through to skull shape and brain functions. These latest results have largely confirmed a separation from our lineage” hundreds of thousands of “years ago. But when the new Neanderthal genome was compared in detail with modern humans from different continents, the results produced an intriguing twist to our evolutionary story: the genomes of people from Europe, China and New Guinea lay slightly closer to the Neanderthal sequence than did those of Africans. Thus if you are European, Asian or New Guinean, you could have 2.5 percent of Neanderthal DNA in your genetic make-up. [Source: Chris Stringer, The Guardian, June 19, 2011. Stringer is head of human origins at the Natural History Museum in London |=|]
“The most likely explanation for this discovery is that the ancestors of today's Europeans, Asians and New Guineans interbred with Neanderthals (or at least with a population that had a component of Neanderthal genes) in North Africa, Arabia or the Middle East, as they exited Africa about 60,000 years ago. That ancient human exodus may have involved only a few thousand people, so it would have taken the absorption of only a few Neanderthals into a group of H. sapiens for the genetic effect – greatly magnified as modern human numbers exploded – to be felt tens of thousands of years later.” |=|
Websites on Neanderthals: Neandertals on Trial, from PBS pbs.org/wgbh/nova; The Neanderthal Museum neanderthal.de/en/ ; Hominins and Human Origins: Smithsonian Human Origins Program humanorigins.si.edu ; Institute of Human Origins iho.asu.edu ; Becoming Human University of Arizona site becominghuman.org ; Hall of Human Origins American Museum of Natural History amnh.org/exhibitions ; The Bradshaw Foundation bradshawfoundation.com ; Britannica Human Evolution britannica.com ; Human Evolution handprint.com ; University of California Museum of Anthropology ucmp.berkeley.edu; John Hawks' Anthropology Weblog johnhawks.net/ ; New Scientist: Human Evolution newscientist.com/article-topic/human-evolution
DNA Studies, Neanderthals and Modern Men
Neanderthal DNA extraction
A study based on genetic material taken the skull of the original Neanderthal specimen found in the Neander Valley in Germany, indicate that Neanderthals were quite clearly a separate species from “Homo sapiens “ and that they probably added nothing to the gene pool of modern humans.
According to a 1997 study by Svante Paabo, then of the University Munich, published the journal Cell, the genetic material of Neanderthals differ about half as much from modern humans as modern humans do from chimpanzees. The study based on studies of Neanderthal mitochondrial DNA, suggests that Neanderthals and “Homo sapiens” had a common ancestor and diverged as separate paths from the “ Homo” family tree about 700,000 to 600,000 years ago. The common ancestor is believed by some to be “Homo heidelbergensis” although other believe that it was an ancestor to Neanderthals alone.
Modern humans differ from each other by an average of eight variations. The DNA taken from the right, upper arm bone of the Neanderthal specimen had 27 difference from modern humans, compared to 55 differences between modern humans and chimpanzees. The Neanderthal DNA differed just as much from modern humans from Africa and Asia as it did from modern humans from Europe. If Neanderthals were in fact ancestors of modern humans it would figure that they would share more genetic material with Europeans than groups from other parts of the world, but this is not case. The discovery of the 160,000-year-old modern human fossils in Ethiopia is further evidence that modern humans and Neanderthals evolved from separate lines.
Neanderthal DNA
In 2005, a team lead by Svante Paabo of the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany announced it was launching a project to reconstruct the Neanderthal genome. In 2006, it announced it had decoded fragments of Neanderthal DNA.
The first draft of the sequence of the Neanderthal genome was published in 2010. As of May 2010, the Neanderthal genome that had been reveled covered about 60 percent of the species full genetic code, with an international team of researchers revealing more ha 3 billion bits of DNA code. . The DNA had been extracted from six skeletons from four sites; the Vindija cave in Croatia, El Sidron in Spain, Mezmaiskaya in Russia and Feldhofer in the Neander Valley of Germany, with three small fragments of bone from Vindija providing most of the sequence.
Svante Paabo Paabo’s team initially examined about 60 Neanderthals of the 400 or so known Neanderthal specimens and found only two with viable genetic material. On top of that less than 5 percent of the material extracted from the bones turned out to be Neanderthal DNA. It took a lot laborious, time-consuming work to map out what they did.
Paabo’s team was able to construct the genome with DNA that has been degraded over time and applied the same technique to reconstructing the genome of mammoths and cave bears. Much of the DNA recovered from Neanderthals bones comes from microorganisms that colonized the tissues after death but enough Neanderthal DNA has been recovered, Paabo said to make it “technically feasible to achieve a reliable Neanderthal genome.” In addition to the colonizing microorganisms, scientists also had to make sure the Neanderthal DNA was not contaminated by human DNA from the scientists working with the samples.
Zach Zorich wrote in Archaeology magazine, “Although this sequence includes only 60 percent of the Neanderthal genome, it does provide some interesting insights into the biology of this distinctive human species. The sequence showed that variations in just one gene might account for the differences in the shape of the skull, rib cage, and shoulder joint between Neanderthals and modern humans. [Source: Zach Zorich, Archaeology magazine, January/February 2011]
A major insight came when researchers compared the Neanderthal DNA to the DNA of three modern people (one French, one Han Chinese, and one Polynesian). The team found that all three had inherited between 1 and 4 percent of their DNA from Neanderthals. They also compared the Neanderthal sequence to two African individuals (one Yoruba and one San) and found no indication that they had inherited genes from Neanderthals, who are known to have evolved outside Africa. The research supports the idea that Neanderthals interbred with Homo sapiens between 100,000 and 80,000 years ago as our anatomically modern ancestors left Africa and spread across the globe. [Ibid]
Sequencing Neanderthal DNA
Elizabeth Kolbert wrote in The New Yorker: The famed evolutionary geneticist Svante Pääbo was in Munich “when he got a call from the Rhenish State Museum, in Bonn. The museum houses the bones of the first Neanderthal to be identified as such, which was discovered in the summer of 1856. What did Pääbo think the odds were that he could extract usable DNA? He had no way of determining what kind of shape the bones were in until he dissolved them. “I didn’t know what to tell them, so I said, ‘There’s a five-per-cent chance that it works,’ ” he recalled. A few months later, he received a small chunk of the Neanderthal’s right humerus.[Source: Elizabeth Kolbert, The New Yorker, August 15, 2011 ]
“Pääbo announced his plan to sequence the entire Neanderthal genome in July, 2006, just in time for the hundred-and-fiftieth anniversary of the Neanderthal’s discovery. The announcement was made together with an American company, 454 Life Sciences, which had developed a so-called “high throughput” sequencing machine that, with the help of tiny resin spheres, could replicate tens of thousands of DNA snippets at a time. Both inside and outside the genetics profession, the plan was viewed as wildly ambitious, and the project made international news. “A STUDY WITH A LOT OF BALLS,” the headline in The Economist declared.
“By this point, a complete version of the human genome had been published. So, too, had versions of the chimpanzee, mouse, and rat genomes. But humans, chimps, mice, and rats are all living organisms, while Neanderthals have been extinct for thirty thousand years. The first hurdle was simply finding enough Neanderthal DNA to sequence. The chunk of the original Neanderthal that Pääbo had received had yielded shreds of genetic information, but nowhere near the quantities needed to assemble—or reassemble—an entire genome. So Pääbo was placing his hopes on another set of bones, from Croatia. (The Croatian bones turned out to have belonged to three individuals, all of them women; the original Neanderthal was probably a man.) “I wish I had that kind of energy.”
“Toward the end of 2006, Pääbo and his team reported that, using a piece of Croatian bone, they had succeeded in sequencing a million base pairs of the Neanderthal genome. (Just like the human genome, the full Neanderthal genome consists of roughly three billion base pairs.) Extrapolating from this, they estimated that to complete the project would take roughly two years and six thousand “runs” on a 454 Life Sciences machine. But later analysis revealed that the million base pairs had probably been contaminated by human DNA, a finding that led some geneticists to question whether Pääbo had rushed to publish results that he should have known were wrong. Meanwhile, subsequent bones yielded a much lower proportion of Neanderthal DNA and a much higher percentage of microbial DNA. (Something like eighty per cent of the DNA that has been sequenced for the Neanderthal Genome Project belongs to microorganisms and, as far as the project is concerned, is useless.) This meant the initial estimates of the labor involved in finishing the genome were probably far too low. “There were times when one despaired,” Pääbo told me. No sooner would one problem be resolved than another materialized. “It was an emotional roller coaster,” Ed Green, the biomolecular engineer from Santa Cruz, recalled.”
Human Neanderthal mtDNA
Neanderthal DNA and Out of Africa
Elizabeth Kolbert wrote in The New Yorker: “About two years into the project, a new puzzle arose. Pääbo had assembled an international team to help analyze the data the sequencing machines were generating—essentially, long lists of A’s, T’s, G’s, and C’s. Sifting through the data, one of the members of this team, David Reich, a geneticist at Harvard Medical School, noticed something odd. The Neanderthal sequences, as expected, were very similar to human sequences. But they were more similar to some humans than to others. Specifically, Europeans and Asians shared more DNA with Neanderthals than did Africans. “We tried to make this result go away,” Reich told me. “We thought, This must be wrong.” [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]
“For the past twenty-five years or so, the study of human evolution has been dominated by the theory known in the popular press as “Out of Africa” and in academic circles as the “recent single-origin” or “replacement” hypothesis. This theory holds that all modern humans are descended from a small population that lived in Africa roughly two hundred thousand years ago. (Not long before he died, Pääbo’s adviser Allan Wilson developed one of the key lines of evidence for the theory, based on a comparison of mitochondrial DNA from contemporary humans.)
“Around a hundred and twenty thousand years ago, a subset of the population migrated into the Middle East, and by fifty thousand years ago a further subset pushed into Eurasia. As they moved north and east, modern humans encountered Neanderthals and other so-called “archaic humans,” who already inhabited those regions. The modern humans “replaced” the archaic humans, which is a nice way of saying they drove them into extinction. This model of migration and “replacement” implies that the relationship between Neanderthals and humans should be the same for all people alive today, regardless of where they come from.”
“Leaky Replacement” Hypothesis
Elizabeth Kolbert wrote in The New Yorker: “Many members of Pääbo’s team suspected another case of contamination. At various points, the samples had been handled by Europeans; perhaps they had got their DNA mixed in with the Neanderthals’. Several tests were run to assess this possibility. The results were all negative. “We kept seeing this pattern, and the more data we got, the more statistically overwhelming it became,” Reich told me. [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]
Gradually, the other team members started to come around. In a paper published in Science, in May, 2010, they introduced what Pääbo has come to refer to as the “leaky replacement” hypothesis. (The paper was later voted the journal’s outstanding article of the year, and the team received a twenty-five-thousand-dollar prize.) Before modern humans “replaced” the Neanderthals, they had sex with them. The liaisons produced children, who helped to people Europe, Asia, and the New World.
“The leaky-replacement hypothesis—assuming for the moment that it is correct—provides further evidence of the closeness of Neanderthals to modern humans. Not only did the two interbreed; the resulting hybrid offspring were functional enough to be integrated into human society. Some of these hybrids survived to have kids of their own, who, in turn, had kids, and so on to the present day. Even now, at least thirty thousand years after the fact, the signal is discernible: all non-Africans, from the New Guineans to the French to the Han Chinese, carry somewhere between one and four per cent Neanderthal DNA.” When Pääbo “finally came around to the idea that Neanderthals bequeathed some of their genes to modern humans, he told me, “I thought it was very cool. It means that they are not totally extinct—that they live on a little bit in us.”“
Neanderthal mtDNA maps
Common Ancestors and DNA Characteristics
Elizabeth Kolbert wrote in The New Yorker: “According to the most recent estimates, Neanderthals and modern humans share a common ancestor...(It is unclear who that ancestor was, though one possibility is the somewhat shadowy hominin known, after a jawbone found near Heidelberg, as Homo heidelbergensis.) The common ancestor of chimps and humans, by contrast, lived some five million to seven million years ago. This means that Neanderthals and humans had less than one-tenth the time to accumulate genetic differences. [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]
“Mapping these differences is, in principle, pretty straightforward—no harder, say, than comparing rival editions of “Hamlet.” In practice, it’s quite a bit more complicated. To begin with, there’s really no such thing as the human genome; everyone has his or her own genome, and they vary substantially—between you and the person sitting next to you on the subway, the differences are likely to amount to some three million base pairs. Some of these variations correspond to observable physiological differences—the color of your eyes, say, or your likelihood of developing heart disease—and some have no known significance. To a first approximation, a human and a Neanderthal chosen at random would also vary by three million base pairs. The trick is ascertaining which of these millions of variations divide us from them. Pääbo estimates that when the Neanderthal Genome Project is completed, the list of base-pair changes that are at once unique to humans and shared by all humans will number around a hundred thousand. Somewhere in this long list will lie the change—or changes—that made us human to begin with. Identifying these key mutations is where the transgenic mice come in.
“From an experimental viewpoint, the best way to test whether any particular change is significant would be to produce a human with the Neanderthal version of the sequence. This would involve manipulating a human stem cell, implanting the genetically modified embryo into a surrogate mother, and then watching the resulting child grow up. For obvious reasons, such Island of Dr. Moreau-like research on humans is not permitted, nor is it necessarily even possible. For similar reasons, such experimentation isn’t allowed on chimpanzees. But it is allowed on mice. Dozens of strains of mice have been altered to carry humanized DNA sequences, and new ones are being created all the time, more or less to order.”
Neanderthal and Human Epigenetics
Epigenetics refers to features of the genome that determine which genes are active and which are inactive, factors that can in turn have a dramatic effect on one’s traits. Zach Zorich wrote in Archaeology magazine: Modern humans share some 99.7 percent of our DNA with Neanderthals. They are our closest evolutionary cousins, but the differences between us run deeper than that 0.3 percent. Much of what distinguishes the two groups is actually the result of how and when genes are expressed and regulated — essentially, turned on and off. Similar, or even identical, stretches of DNA can produce vastly different traits, such as longer limbs or smaller brains, depending on how and when certain genes are actively producing protein. The study of these processes is known as epigenetics. [Source:Zach Zorich, Archaeology magazine, July-August 2014]
Daniel Weiss wrote in Archaeology magazine: .Now, researchers from Hebrew University in Jerusalem and the Max Planck Institute for Evolutionary Anthropologyhave found an ingenious way to investigate Neanderthal epigenetics. Their findings have provided tantalizing clues to how the bodies and brains of modern humans have evolved since splitting from Neanderthals several hundred thousand years ago. The usual methods for determining whether genes are active or inactive are highly destructive and cannot be used on scarce Neanderthal genetic material. Instead, the researchers managed to detect telltale epigenetic signs in the Neanderthal genome based on the insight that certain portions of ancient DNA tend to be misread in a distinctive way by DNA sequencers. [Source:Daniel Weiss, Archaeology magazine, January-February 2015]
“This reading of Neanderthal epigenetics produced a number of novel results. Two genes involved in determining body shape turned out to be highly inactivated in Neanderthals and highly activated in humans. This could help explain why Neanderthals have thicker hands, wider knee and elbow joints, and shorter limbs. “These genes are identical between us and Neanderthals,” says Liran Carmel of Hebrew University. “So we are convinced we have found a region where only the epigenetics is different.”
Studying epigenetic differences between humans and Neanderthals is of equal importance to studying the genetic differences,” says Carmel. By looking at the way that Neanderthal DNA chemically degraded over millennia in the ground, the researchers were able to reconstruct how certain molecules, called methyl groups, were attached to the DNA. Methyl groups can help determine how much of a particular protein a gene creates. The research showed that certain Neanderthal genes had different patterns of attached methyl groups, compared with corresponding portions of the modern human genome. As a result, strikingly similar stretches of DNA could produce two very different hominins.
“For example, two genes involved in limb development have different patterns of methyl groups, which may be why we have longer arms and legs than Neanderthals did. Similar differences were observed in genes associated with brain development and susceptibility to certain diseases. Carmel believes that as more Neanderthal DNA is analyzed, we will begin to understand the evolutionary changes that created the modern human. “There is a huge potential,” he says. “Studying epigenetic characteristics could be of great importance for zooming in on the properties that have shaped what we are today.”
FOXP2 and RUNX2 — Genes Involved in Language and Bone Formation
Elizabeth Kolbert wrote in The New Yorker: “Several years ago, Pääbo and a colleague, Wolfgang Enard, became interested in a gene known as FOXP2, which in humans is associated with language. (People who have a faulty copy of the gene—an extremely rare occurrence—are capable of speech, but what they say is, to strangers, mostly incomprehensible.) Pääbo and Enard had some mice bred with a humanized version of the gene, and then studied them from just about every possible angle. The altered mice, it turned out, squeaked at a lower pitch than their un-humanized peers. They also exhibited measurable differences in neural development. (While I was in Leipzig, I watched a graduate student cut the heads off some of the altered mice and then slice up their brains, like radishes.) [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]
“The Neanderthals’ FOXP2 gene, it turns out, is in almost all ways identical to humans’, but there is one suggestive base-pair difference. When this difference was discovered, it prompted Pääbo to order up a new round of transgenic mice, which, at the time of my visit, had just been born and were being raised under sterile conditions in the basement.
“Genes that seem to play a role in speech are obvious places to look for human-specific changes. But one of the main points of sequencing the Neanderthal genome is that the most obvious places to look may not be the right ones. “The great advantage with genomics in this form is that it’s unbiased,” Pääbo told me. “If you go after candidate genes, you’re inherently saying what you think the most important thing is. Language, many people would say. But perhaps we will be surprised—perhaps it’s something else that was really crucial.”
“Recently, Pääbo has become interested in a gene known as RUNX2, which is involved in bone formation. When members of his team analyzed the human and Neanderthal genomes mathematically, RUNX2 emerged as a place where significant changes in the human lineage seem to have occurred. People who have faulty copies of the RUNX2 gene often develop a condition, known as cleidocranial dysplasia, whose symptoms include such Neanderthal-like features as a flared rib cage. Two genes that have been implicated in autism, CADPS2 and AUTS2, also appear to have changed substantially between Neanderthals and humans. This is interesting because one of the symptoms of autism is an inability to read social cues.”
Neanderthal DNA comparison
Fifth of Neanderthals' DNA Lives on in Modern Humans
About a fifth of the DNA carried today by the human population was also carried by Neanderthals, a result of sexual encounters scientists estimate took place Neanderthals and modern humans as they migrated out of Africa and into Eurasia about 65,000 years ago. Ian Sample wrote in The Guardian: “The populations of both groups were likely so small that interbreeding was a rare event, but the benefits of some Neanderthal genes were so great that they spread through the population and linger on in modern non-Africans today. The finding means that scientists can study about 20 percent of the Neanderthal genome without having to draw the genetic material from fragile and ancient fossils. [Source: Ian Sample, The Guardian, January 29, 2014]
“Benjamin Vernot and Joshua Akey at the University of Washington in Seattle sequenced the genomes of more than 600 people from Europe and eastern Asia. They then used a computer analysis to find gene variants that bore all the hallmarks of having come from Neanderthals. To see whether the technique worked, they checked the genes against the official Neanderthal genome, which was sequenced from fossil remnants in 2010 by researchers in Germany. |=|
“The researchers found that while most non-Africans carried 1 to 3 percent Neanderthal DNA, the total amount in modern humans reached about 20 percent. "Although Neanderthals are extinct, there's still a lot of genetic information about them floating around, in our own genomes. It's not necessarily useful in that it will cure cancer, but it helps us to learn about our history," Vernot told the Guardian. Details of the study are reported in Science. The researchers now believe that even deeper mining of modern genomes could help to find genetic traces of other archaic humans. |=|
“In a separate study published in Nature, David Reich at Harvard University looked for Neanderthal genes in the DNA of more than 1,000 living people. He found that the Neanderthals left a mark in distinct regions of the modern human genome, but in others left no trace at all. Many of the Neanderthal genes that live on in people today are involved in making keratin, a protein used in skin, hair and nails. Reich speculates that modern humans may have picked up Neanderthal genes that were better suited to the cold environment, perhaps because they produced more or thicker hair, or tougher skin. |=|
“More striking was that humans are missing Neanderthal DNA from many other regions of their genomes, which suggests that evolution steadily stripped the archaic DNA out until it vanished all together. Reich found that hardly any Neanderthal genes were expressed in modern men's testes, and that the X chromosome was almost completely devoid of Neanderthal DNA. That would happen if males with Neanderthal and modern human parents were infertile, because the males would never get to pass on their single Neanderthal X chromosome. "When Neanderthals and modern humans interbred they were actually at the edge of biological compatibility. They did interbreed, and Neanderthals left an important biological trace in modern humans, but nevertheless, the population had to sort out some problems afterwards, because certain Neanderthal variants led to reduced male fertility," said Reich. The finding suggests that most Neanderthal DNA found in humans today was passed down from females. |=|
"Anything related to maleness in the Neanderthal has been purged from our genomes," said Chris Stringer, head of human origins at the Natural History Museum in London. "Neanderthal DNA has come down to us today, but that transmission was mainly through the female line, because the males would have been significantly less fertile, and possibly even sterile." |=|
DNA IBD segment detected by HapFABIA in 1000 Genomes
Neanderthal DNA in Humans: Result of Common Ancestor Rather Than Sex
A study published in 2012 by researchers from the University of Cambridge in the journal Proceedings of the National Academy of Sciences. challenges the view humans and Neanderthals had inter-species sex, known as hybridisation, and said a better explantion for the presence of Neanderthal DNA in modern humans was the sharing a common ancestor. Mehreen Khan of Bloomberg wrote: “The Cambridge researchers examined demographic patterns suggesting humans were far from intimate with the species they displaced in Europe almost 40,000 years ago. ''The levels of hybridisation people have spoken about is too high,'' said Andrea Manica, a researcher from Cambridge University who wrote the study. ''If any hybridisation happened, then it would have been minimal.'' [Source: Mehreen Khan, Bloomberg, August 23, 2012 ||^||]
“A previous study in 2010 suggested that inter-species liaisons near the Middle East resulted in Neanderthal genes first entering humans 70,000 years ago. Modern non-Africans share more with Neanderthals than Africans, supporting the claim that the mixing occurred when the first early humans left Africa to populate Europe and Asia. ||^||
“The existence of a 500,000-year-old shared ancestor that predates the origin of Neanderthals provides a better explanation for the genetic mix, the Cambridge scientists said. Diversity within this ancestral species meant that northern Africans were more genetically similar to their European counterparts than southern Africans through geographic proximity, Manica said. This likeness persisted over time to account for the overlap with the Neanderthal genome we see in modern people today. ''Differences between populations can be explained by common ancestry,'' said Manica, whose research was funded by the Biotechnology and Biological Sciences Research Council and the Leverhulme Trust. ''Northern Africans would be more similar to Europeans and ancient similarity stayed because there wasn't enough mixing between northern and southern Africans.'' ||^||
“Population diversity, known as substructure, can't explain data on the shared genes, said David Reich, a professor of genetics at Harvard Medical School in Boston and author of the 2010 study. ''We have ruled out the possibility that ancient substructure can explain all the evidence of greater relatedness of Neanderthals to non-Africans than to Africans,'' Reich said. Hybridisation between Neanderthals and humans can never be disproved entirely, according to Manica, who questioned what inter-species breeding may mean for the human genome today. ''The further we bring down the level of hybridisation, the more unlikely it is it would have shaped the ways modern humans evolved,'' Manica said. ||^||
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Last updated April 2024