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Denisovans

Denisovans


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Denisovans are an extinct species of hominid and a close relative to modern humans. They’re a recent addition to the human family tree—scientists first identified Denisovan remains from a cave in Siberia in 2010. Denisovans may have ranged from Siberia to Southeast Asia during the last Ice Age. DNA evidence suggests Denisovans are related to both Neanderthals and modern humans, and may have interbred with both.

Denisovans share a common ancestor with both modern humans and Neanderthals. This common ancestor, called Homo heidelbergensis, most likely lived in Africa.

Between 300,000 and 400,000 years ago, one group of Homo heidelbergensis left Africa. They expanded into Eurasia and then split: Those that moved west into Europe evolved into Neanderthals. The ones that moved east into Asia became Denisovans.

The human ancestors that remained in Africa evolved into our own species—Homo sapiens. Modern humans and Denisovans likely met for the first time in Eurasia some 40,000 to 60,000 years ago, after Homo sapiens began their own migration out of Africa.

Denisovan Discovery

Denisovans are a relatively recent discovery: In 2008, Russian paleoanthropologists exploring Siberia’s Denisova Cave—located in the Altai Mountains along Russia’s southern border with China and Mongolia—found a tiny, pea-sized fragment of finger bone.

They determined the fossilized pinkie bone had belonged to a young girl between the ages of about five and seven when she died roughly 40,000 years ago. Cold weather in the Siberian cave helped to preserve ancient DNA.

In 2010, a group of scientists led by Svante Paabo of the Max Planck Society in Germany extracted DNA from the tiny bone fragment.

Scientists sequenced the girl’s genome and compared it to the genomes of modern humans and Neanderthals—two other hominin species known to be living in Eurasia at the time. Studies showed that the girl was genetically similar to both Neanderthals and Homo sapiens, but distinct enough to be considered a new species of human.

The researchers named the archaic humans Denisovans after the cave in Siberia where the fossil was discovered. Scientists have since discovered fossilized teeth from three other Denisovan individuals—all from inside Denisova Cave.

Denisovan DNA

Since very few Denisovan fossils have been found, most of what we know about the extinct humans comes from their DNA.

It’s not clear when exactly Denisovans evolved—or when they went extinct—but DNA evidence suggests they were living in Asia at least 80,000 years ago. They may have had dark skin, dark hair and dark eyes. The Denisovan genome appears to have low genetic diversity, which means their population may never have been very large.

Researchers believe that modern human ancestors may have interbred with Denisovans. Denisovan DNA can be found in the human genome.

Melanesians

Some present-day East Asian groups, in particular Melanesians, may have inherited up to five percent of their genetic material from Denisovans. Melanesians are Pacific Islanders native to a region spanning from Papua New Guinea to Fiji.

Scientists theorize that Denisovans living in East Asia may have interbred with the ancestors of present day Melanesians before those humans crossed the Pacific Ocean to reach Papua New Guinea approximately 45,000 years ago.

Tibetans and Han Chinese have traces of Denisovan DNA in their genomes too. In 2014, researchers discovered that ethnic Sherpas likely inherited from Denisovans a “super athlete” gene variant that helps them breathe easily at high altitudes.

Sources

Why Am I Denisovan?, National Geographic.
Genetic history of archaic hominin group from Denisova Cave in Siberia, Nature.
Tibetans inherited high-altitude gene from ancient human, Science Magazine.


In 2008, Russian scientists Michael Shunkov (paleontologist) and Anatoly Derevianko (archaeologist) discovered a terminal finger phalanx from a young girl, dubbed “X-woman,” in the Denisova Cave in the Altai Mountains of Russia (see Figures 34.1 and 34.2). The Denisovans, as they have come to be called, inhabited the cave by 50 kya.

The phalanx was sequenced by Svante Pääbo’s lab at the Max Planck Institute, where it was determined to be from a new form of extinct hominin. Its ancestor is thought to have split from our own lineage by >800 kya, subsequently splitting into the Denisovan and neandertal lineages

640 mya (Callaway 2013). The two resulting lineages remained as genomically alike as two geographically distant modern human populations. Pääbo (2014) uses the example of Finns and the San people of South Africa. It is estimated that gene flow from neandertals to Denisovans was fairly low (≥0.5%) and seemingly occurred only locally in the Altai region (Prüfer et al. 2013). What is even more interesting from our perspective is that Denisovans seem to have interbred with the first wave of AMH as they passed through southern Asia after leaving Africa. These humans already carried neandertal genes from having interbred with them. Thus modern human populations that have descended from those early humans (i.e. indigenous Melanesians, Polynesians, Australians, and some Filipinos) carry 4.8% Denisovan genes, along with the mean of 2.5% neandertal genes that all Eurasians possess, meaning that a total of

7% of their genes are derived from extinct hominins! Genes for dark skin, hair, and eyes were present in the Denisovan genome and are present in modern Melanesians (Marshall 2013). This is fascinating from two perspectives. First, it is interesting that those ancestral characteristics survived in a modern population. Second, we now know something about what the Denisovans likely looked like. Wow!

The Denisovan-like genes that the rest of Eurasians possess may have been inherited from neandertals, due to their close genetic relationship with the Denisovans. It is of great interest that the genetic variability in one of our important immunological systems, the human leucocyte antigen (HLA) system, is probably due to interbreeding with neandertals. Half of the HLA variant genes, termed alleles, seen in Eurasian populations are derived from those two extinct species (Abi-Rached et al. 2011). What is fascinating is that those alleles likely conferred a selective advantage on some of our ancestors, and they thus survived in their descendants. It is likely that neandertals and Denisovans inherited the allele(s) from H. heidelbergensis, lending further support for the latter species having diverged from our lineage prior to the mutation(s) that led to the forms present in the former two species.

Finally, a variant of the EPAS1 gene in Tibetans has also been traced to the Denisovans. The allele is an adaptation to the hypoxic (i.e. low oxygen) conditions of high altitude. The allele affords those individuals with better oxygen metabolism capabilities (Huerta-Sanchez et al. 2014).

Mitochondrial DNA (mtDNA) from a 400 kya femur from the Sima de los Huesos site in Spain has been found to most closely resemble Denisovans (Callaway 2013). The site contains Homo heidelbergensis material, and if the leg bone is from an individual of that species, it will further muddy the phylogenetic waters. However, it must be remembered that mtDNA gives only maternal lineage information, and it is thus possible that the individual was not more closely related to Denisovans but that the mtDNA alleles were conserved in his or her lineage.

Denisova Cave. “Turist den-peschera” by ЧуваевНиколай at ru.wikipedia is licensed under CC BY-SA 3.0.


Human health to heady history

Cox and his colleagues didn't initially set out to search for Denisovan diversity. Instead, the team was interested improving healthcare in Indonesia and neighboring regions in Island Southeast Asia. A better understanding of the gene variants related to disease in the region could lead to treatments targeted more specifically to those populations.

“It’s very important to us,” says study author Herawati Sudoyo, senior research fellow at Indonesia's Eijkman Institute, which partnered with an international team for this latest work. While Indonesia is a hugely diverse country that hosts many genetically distinct people, she notes that “there was no genetic study being done because…the technology was not [yet] here in Indonesia.”

Among the genetic differences distinguishing those diverse groups were ones with tell-tale signs that the splits between populations occurred deep in the past. Interbreeding between H. sapiens arriving from their African homeland and other ancient humans inserted tidbits of DNA from those archaic relatives that are passed from generation to generation to the present. Today, non-African populations have up to two percent Neanderthal DNA, some of which is beneficial and help human immune systems guard against infectious disease.

But Neanderthals weren't the only human relative with which H. sapiens interbred after they trekked out of Africa some 64,000 years ago. Most people of Asian descent carry some amount of Denisovan DNA, but it's particularly high in Melanesians, whose genomes are up to six percent Denisovan. It's thought that the ancestors of modern Melanesians met and mated with these ancients en route to their island home.

To dive deeper into this legacy, Cox and his team sequenced 161 genomes from 14 island groups across Indonesia and New Guinea. They combined this data with 317 genomes from around the world and compared all of the data to genomes from both Neanderthals and the Altai Denisovan. As they lined up the ancient Denisovan DNA with the Denisovan bits of modern Papuans, the team expected to see just a single spike, where modern Papuan DNA clustered. Instead, it split into two strikingly separate peaks.

“It was either the world’s most boring artifact or it was something that was going to be really, really cool,” Cox says.


The evolutionary history of Neanderthal and Denisovan Y chromosomes

Ancient DNA has provided new insights into many aspects of human history. However, we lack comprehensive studies of the Y chromosomes of Denisovans and Neanderthals because the majority of specimens that have been sequenced to sufficient coverage are female. Sequencing Y chromosomes from two Denisovans and three Neanderthals shows that the Y chromosomes of Denisovans split around 700 thousand years ago from a lineage shared by Neanderthals and modern human Y chromosomes, which diverged from each other around 370 thousand years ago. The phylogenetic relationships of archaic and modern human Y chromosomes differ from the population relationships inferred from the autosomal genomes and mirror mitochondrial DNA phylogenies, indicating replacement of both the mitochondrial and Y chromosomal gene pools in late Neanderthals. This replacement is plausible if the low effective population size of Neanderthals resulted in an increased genetic load in Neanderthals relative to modern humans.


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A human skull from 34,000 years ago found in Mongolia elucidates the genetics of early East Asians and Denisovan admixture.


Neanderthal and Denisovan Genes – and Covid-19

The media reported last week that genes from Neanderthals protect many of us against severe Covid-19. Those genes actually come from Denisovans too: another early human species. Unfortunately, a different set of Neanderthal genes increases our chances of serious Covid. This post goes behind the news and looks at our connection to these two prehistoric creatures, as well as their genes’ impact on Covid risk. It also looks at those genes’ frequency among modern ethnic groups.

Neanderthal woman (from the Neanderthal Museum)

Neanderthals and Denisovans

We’ve known about Neanderthals since the 1860s, and archeologists have found hundreds of their fossils and tools. Denisovans, however, were only identified in 2010. Much about them remains unclear, and we only have a handful of fossils. But we know they had bigger molars than Neanderthals or Homo sapiens — more like earlier members of the Homo genus. We also know Denisovans shared the Neanderthals’ massive build, flat noses, protruding jaws and brow-ridges, sloping foreheads, and flat and long heads. Those oddly shaped Neanderthal heads contained brains bigger than ours, so Denisovans may have had bigger brains too. We don’t know whether that means these other species were smarter.

Fortunately, we have both species’ DNA, extracted from the fossils.

Classification and Hybrids

The Neanderthals and Denisovans are classified Homo neanderthalensis and, tentatively, Homo denisova. They evolved in Eurasia from a shared ancestor called Homo heidelbergensis. We’re their smaller, weaker African cousins. Our species probably descends from Homo heidelbergensis too, but the Homo sapiens branch of the tree diverged earlier. Still, we were close enough to cross-breed and produce fertile offspring.

Members of different species usually can’t do that: they can’t produce fertile offspring. Horses and donkeys can’t, even though they’re closely related — members of the Equus genus. Cross-breeding them produces sterile mules (and hinnies). The same goes for lions and tigers, members of the Panthera genus, which produce sterile hybrids called ligers and tigons. So we must have been very closely related to Neanderthals and Denisovans — closer than horses and donkeys or lions and tigers. It’s not unprecedented. Wolves and coyotes can produce fertile offspring. So can cows and buffalo, as well as servals and housecats, which have been bred to produce a beautiful spotted pet called a Savannah cat. In each case, some of the hybrid offspring may be sterile, particularly among the males. But enough can reproduce to pass on hybrid genes.

The convoluted Homo genus family tree. The vertical axis measures time in millions of years past.

Prehistoric Encounters and Modern Ethnic Groups

We met Neanderthals and Denisovans when our species spread out from Africa into Eurasia, around 60,000 years ago. So their genes occur among Europeans and Asians. They’re also found among Native Americans, Australian Aboriginals, North Africans, and all other peoples who migrated through Eurasia before reaching their long-term homes. Europeans and mainland Asians average something like 2% Neanderthal, while Australian Aboriginals, Polynesians, and Indonesians range from 1% to 6% Denisovan. And many in those populations have some of both.

Only Sub-Saharan Africans lack significant Neanderthal or Denisovan genes. That’s because their ancestors did not migrate through Eurasia. Prehistoric Africans may have interbred with non-sapiens too, but those would’ve been African species, so far unidentified.

Of course, members of every ethnic group usually have some ancestors from another group. So as they say with medicines, individual results may vary.

The Hybrids’ Helpful Haplotypes

Last month, scientists announced a haplotype — a cluster of genes — that helps destroy RNA viruses, including Covid-19. Each copy of the haplotype reduces the odds of severe Covid by 22%. That haplotype occurs in Neanderthals and Denisovans but not in early Homo sapiens. Our species got it from the other two species — from cross-breeding.

DNA is rarely simple, however, and neither is immunity. Scientists have also identified a Neanderthal haplotype that increases the risk of severe Covid-19. Those genes double our chances of hospitalization. They don’t seem to come from Denisovans.

Today’s Ethnic Groups and Natural Selection

The currently helpful haplotype appears in about 50% of non-Africans. That’s a lot for genes from Neanderthals and Denisovans, since each represents such a small share of our genetic inheritance. So that haplotype probably protected us against Covid-like viruses in the past, leading to heavy selection for those genes. In fact, the haplotype’s frequency apparently surged during just the past thousand years (in addition to earlier increases). That suggests we faced a Covid-like disease recently: during the Middle Ages (the Postclassical period) or later.

The currently harmful Neanderthal haplotype appears in about 65% of Southeast Asians and 16% of Europeans. It’s mostly absent from East Asians and of course from Africans. That haplotype probably protected against diseases faced by Southeast Asians in the past and so grew more common there. But its vulnerability to Covid-like diseases led to selection against those genes in other regions.


Who were the Denisovans?

We currently know much more about the DNA of Denisovans than we do about their physical appearance, as hominin fossils are exceedingly rare at the site.

Besides the fingerbone, a total of three teeth have been genetically identified as Denisovan. The DNA from a tiny fragment of long bone from the daughter of Denisovan and Neanderthal parents provides direct evidence that the two groups met and interbred at least once.

We know frustratingly little about the geographic distribution and demography of the Denisovans, except for the head-scratching finding that Aboriginal Australians and New Guineans are the only people alive today with substantial amounts of Denisovan DNA in their genome.

But while hominin fossils are few and far between at Denisova Cave, the deposits contain thousands of artefacts made from stone. The upper layers also contain artefacts crafted from other materials, including ornaments made of marble, bone, animal teeth, mammoth ivory and ostrich eggshell. There are also animal and plant remains that bear witness to past environmental conditions.

Selection of artefacts from Denisova Cave. a, Upper Palaeolithic b, Initial Upper Palaeolithic c, middle Middle Palaeolithic and d, early Middle Palaeolithic. Institute of Archaeology and Ethnography of the Siberian Branch of the Russian Academy of Sciences , Author provided


Who were the Denisovans? The ancient human is still an enigma

Plus: The terrible science behind popular weight loss products.

Elena Zavala, a researcher at the Max Planck Institute for Evolutionary Anthropology, puts it plainly: very little is known about the Denisovans.

“This is a group we know very little about,” Zavala tells Inverse’s Tara Yarlagadda in our lead story. “By increasing our knowledge, we are provided with another perspective or reference for understanding what are the elements that make us modern humans ‘human.’”

In a remote cave nestled in the Altai Mountains of southern Russia, scientists have extracted DNA from ancient sediment that suggests the Denisovans lived there before, and then during the time of the Neanderthals. They lived there up until around 45,000 years ago. The research was published Wednesday in the journal Nature.

Our understanding of who exactly the Denisovans were is still murky, but it’s one that’s steadily becoming improved. Keep scrolling down to read more on this fascinating story of ancient history that’s being uncovered today.

Mailbag — What’s in your apocalypse bag? You know, the backpack you carry when the world ends. We’ve put together a reader poll just for the Inverse Daily community. Take the anonymous survey here.

This is an adapted version of theInverse Daily newsletter for June 24, 2021.Subscribe for free and earn rewards for reading every day in your inbox.

A cave in Russia could solve an ancient mystery Scientists discovered that a little-known group of ancient people, the Denisovans, may predate the Neanderthals at a site important to the story of humankind. Tara Yarlagadda has the story:

In a remote cave nestled in the Altai Mountains of southern Russia, scientists are uncovering the secrets of ancient human life. Here in this cave, ancient peoples like the Neanderthals found shelter from the bitter chill of the Ice Age.

According to new research, Neanderthals also shared this cave with another little-known group of ancient humans: the Denisovans. Furthermore, the Denisovans were likely there first.

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He cited a study he claimed proved it. People, he said, didn’t need to change what they ate or how they exercised. They could simply “do whatever they wanted to do” and in the process lose “a pound per week.”

Spoiler alert: the study was bad and the data flawed. Green coffee bean extract amounted to an expensive placebo and six years later Dr. Oz lost a $5.25 million lawsuit over the false advertising.

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DISCOVERY AND GEOGRAPHIC RANGE

In addition to Denisova Cave, Shunkov and Derevianko also found bone fragments in the nearby Okladnikov Cave. They have since recovered two teeth and a toe bone.

The caves were also occupied by neandertals and humans at various times over the millennia. Prior to the discovery of neandertals in the area, it was thought that they ranged no farther east than Uzbekistan. This new discovery extends their geographic range by 2,000 km. The Denisovans also must have had a large geographic range, since they are thought to have bred with AMH as they passed through southern Asia (see Figure 34.3). It is amazing that for over 100 years, the only extinct hominins that we knew of in the northern hemisphere were the erectus-forms and neandertals and now, in just the last couple of years, we have two more, the Denisovans and the Red Deer Cave hominins. (Pääbo 2014, unless otherwise indicated.)

Figure 34.3 Possible routes taken by Late Pleistocene hominins. “Spread and evolution of Denisovans” by John D. Croft at English Wikipedia is licensed under CC BY-SA 3.0.


Denisovan DNA may have aided Pacific migration

Genomic study traces the spread of humans across the Oceanic region.

An international team of scientists has delved into the genetics of the Pacific population to trace the history of human settlement across the vast region – with a few surprising results.

By examining the genomes of 317 present-day individuals from 20 populations, the team found that the ancestors of modern-day Pacific populations interbred with little-understood ancient hominins called Denisovans. This genetic mixture seems to have bolstered the immune system and helped these early explorers adapt to living on isolated islands. The results may have implications for the health of Pacific populations today.

What do we know about the peopling of the Pacific?

The population of the Pacific is one of the most impressive feats of exploration in human history. The Pacific Ocean is the single largest feature on the planet, sprinkled with islands that are fairly close together in the west but separated by larger and larger gaps towards the east, until there are thousands of kilometres between landmasses.

This enormous region is divided into Near Oceania (including Papua New Guinea, the Bismarck Archipelago and the Solomon Islands) and Remote Oceania (Micronesia, Santa Cruz, Vanuatu, New Caledonia, Fiji and Polynesia).

Our current understanding is that after humans migrated out of Africa, they flowed down through South East Asia, hopping across narrow straights and between islands. From Timor, they used rudimentary rafts or dugout canoes to cross to Papua New Guinea, then headed down the scythed curve of the Bismarck Archipelago, and reached the far edge of the Solomon Islands by around 40,000 years ago. There, nothing but the open ocean lay ahead of them, and so these people – the Near Oceanians – stopped, and Remote Oceania remained uninhabited.

Then some 5,000 years ago, a group of humans from what is now Taiwan left their home shores and journeyed south through the Philippines and Indonesia into Near Oceania. Called Austronesians, they brought with them sophisticated maritime technology and seafaring skills. They mixed with populations of the Near Oceanians, forging a new people – the Lapita – who then struck out to populate the rest of the Pacific.

What does this new study add?

The new genetic analysis suggests that the gene pool of the ancestors of Near Oceanians underwent a drastic reduction just before they settled in the region, with an effective population size of 214. The study also dated the settlement of Near Oceania to around 40,000 years ago, confirming archaeological records, and found evidence that after settling, the populations of different islands generally kept to themselves.

“Our results confirm that humans were able to cross the seas to reach new lands from an early stage,” explains co-author Etienne Patin, from the French National Centre for Scientific Research. “However, they also suggest that these voyages were relatively infrequent at this distant period in history.”

The study sheds light on the expansion of the Austronesian people out of Taiwan, suggesting that their dispersal wasn’t followed by a single event of mixing with Near Oceanian populations, but rather involved several recurring episodes.

“Our analyses suggest that humans left Taiwan more than 5,000 years ago, and that admixture between the Austronesian incomers and the populations of Near Oceania started only 2,000 years later,” Patin says. “The expansions from Taiwan therefore took some time, and may have involved a maturation phase in the Philippines or Indonesia.”

The study also revealed the percentage of ancient human DNA present in modern-day Pacific populations. While all humans outside of Africa have inherited Neanderthal DNA (2-3%), some Pacific populations also have inherited up to 3% of their genomes from Denisovans.

But surprisingly, as co-author Lluis Quintana-Murci from the Collège de France notes, “the Denisovan legacy varies considerably between populations, from virtually 0% in Taiwan and the Philippines to up to 3.2% in Papua New Guinea and Vanuatu”.

Previous work has shown that Neanderthal DNA has improved the adaptive capacity of modern humans, with beneficial mutations including those related to skin pigmentation, metabolism, and neural development. This new study now shows that admixture with Denisovans bolstered the immune system of Pacific populations, which may have helped humans adapt to and survive local pathogens when they spread into isolated island environments.

Plus, the mixing between humans and Denisovans didn’t occur just once – at least four independent mixing events occurred with at least two different lineages of Denisovans, as recently as 21,000 years ago. Two of these mixing events occurred after the emergence of the Lapita culture.

“Collectively, our analyses show that interbreeding between modern humans and highly structured groups of archaic hominins was a common phenomenon in the Asia-Pacific region,” the authors write in their paper.

Quintana-Murci notes that this also improves our understanding of the elusive Denisovans, a species for which we have very little fossil evidence.

“One of the strengths of these analyses is that, by studying the 3% of archaic heritage present in the genomes of modern humans, one can ‘resurrect’ Denisovans’ genomes, and thus show that they presented high levels of genetic diversity,” he says.

According to Murray Cox, a computational genomics researcher from Massey University in New Zealand, this is a “fascinating” result.

“The field has long held an implicit assumption that modern human admixture with Denisovans occurred in much the same way it did with Neanderthals,” explains Cox, who was not involved in the study but has worked on similar research. “This paper clearly shows that assumption is unfounded.

“Mixing between modern humans and archaic groups was much more structured, and occurred much later, in the Asia-Pacific region. It appears that Denisovans persisted in Oceania long after modern humans arrived, and sharing territory with archaic hominins was part of the modern human story for a long period of our history.”

The team also found that in the ancestors of modern-day Pacific populations, genes associated with lipid metabolism were selected for, which may further our understanding of why Pacific populations have been observed to suffer a high burden of metabolic disease, including obesity and type 2 diabetes.

“Large genomic studies in the Pacific region are required to understand the causal links between past genetic adaptation and present-day disease risk, and to promote the translation of medical genomic research in understudied populations,” the authors conclude.

Lauren Fuge

Lauren Fuge is a science journalist at The Royal Institution of Australia.

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