DNA Sequencing Megathread! Neanderthals, Denisovans and other ancient DNA!

[jimmy olsen]

Cool!

https://news.nationalgeographic.com/2018/04/bajau-sea-nomads-free-diving-spleen-science/

'Sea Nomads' Are First Known Humans Genetically Adapted to Diving

For hundreds of years, the Bajau have lived at sea, and natural selection may have made them genetically stronger divers.

By Sarah Gibbens

PUBLISHED April 19, 2018

If you hold your breath and plunge your face into a tub of water, your body automatically triggers what's called the diving response. Your heart rate slows, your blood vessels constrict, and your spleen contracts, all reactions that help you save energy when you're low on oxygen.

Most people can hold their breath underwater for a few seconds, some for a few minutes. But a group of people called the Bajau takes free diving to the extreme, staying underwater for as long as 13 minutes at depths of around 200 feet. These nomadic people live in waters winding through the Philippines, Malaysia, and Indonesia, where they dive to hunt for fish or search for natural elements that can be used in crafts.

Now, a study in the journal Cell offers the first clues that a DNA mutation for larger spleens gives the Bajau a genetic advantage for life in the deep.

Leaning on the Spleen

Of all the organs in your body, the spleen is perhaps not the most glamorous. You can technically live without it, but while you have it, the organ helps support your immune system and recycle red blood cells.

Previous work showed that in seals, marine mammals that spend much of their life underwater, spleens are disproportionately large. Study author Melissa Llardo from the Center for Geogenetics at the University of Copenhagen wanted to see if the same characteristic was true for diving humans. During a trip to Thailand, she heard about the sea nomads and was impressed by their legendary abilities.

"I wanted to first meet the community, and not just show up with scientific equipment and leave," she says of her initial travels to Indonesia. "On the second visit, I brought a portable ultrasound machine and spit collection kits. We went around to different homes, and we would take images of their spleens.

"I usually had an audience," she adds. "They were surprised I had heard of them."

She also took data from a related group of people called Saluan, who live on the Indonesian mainland. Comparing the two samples back in Copenhagen, her team found that the median size of a Bajau person's spleen was 50 percent bigger than the same organ in a Saluan individual.

"If there's something going on at the genetic level, you should have a certain sized spleen. There we saw this hugely significant difference," she says.

The researchers also stumbled across a gene called PDE10A, which is thought to control a certain thyroid hormone, in the Bajau but not the Saluan. In mice, the hormone has been linked to spleen size, and mice that are manipulated to have lower amounts of the hormone have smaller spleens.

Llardo theorizes that over time, natural selection would have helped the Bajau, who have lived in the region for a thousand years, develop the genetic advantage.

Under Pressure

While the spleen might partially explain how the Bajau dive so well, other adaptations may be at play, too, says Richard Moon from the Duke University School of Medicine. Moon studies how the human body responds to both high altitudes and extreme depths.

As a human dives deeper into the water, the increase in pressure causes the lung's blood vessels to fill with more blood. In extreme cases, the vessels can rupture, causing death. In addition to genetically inherited adaptations, regular training could help prevent that effect.

"The lung chest wall could become more compliant. There could be some looseness that develops over your training. The diaphram could become stretched. The abs could become more compliant. We don't really know if those things occur," he says. "The spleen is able to contract to some extent, but we don't know of any direct connection between thyroid and spleen. It may well be."

Cynthia Beall is an anthropologist from Case Western Reserve University who has studied people living in extremely high altitudes, including Tibetans said to live at the "roof of the world." She thinks Llardo's study opens up interesting research opportunities but needs to see more measurable biological evidence before she's convinced that a genetic trait is helping the Bajau become better divers.

"You could measure the spleen more, for example, strength of contractions of the spleen," she says.

What Can We See From the Sea?

In addition to understanding how the Bajau became such good free divers, Llardo says the findings have medical implications.

The dive response is similar to a medical condition called acute hypoxia, in which humans experience a rapid loss of oxygen. The condition is often a cause of death in emergency rooms. Studying the Bajau could effectively act as a new laboratory for understanding hypoxia.

However, the sea nomad lifestyle is increasingly under threat. They're considered marginalized groups that don't enjoy the same citizenship rights as their mainland counterparts. Increased industrial fishing is also making it harder for them to subsist on local stocks. As a result, many choose to leave the sea.

Without support for their way of life, Llardo worries that the Bajau and the lessons they can impart about human health may not be around for much longer.

[Josquius]

Tyr, much of my English ancestry comes from North Yorkshire  (a couple of origin towns that come to mind are Rillington and Scampston) and I've connected with enough distant relatives that share that ancestry, including folks that still live in Yorkshire, to conclude that Ancestry sees folks from that area as largely 'Scandinavian'.  Makes sense as the Norse are thought to have heavily settled it back in the day.

Yeah, it's why I was expecting a lot more than what I got.
I wonder whether it suggests that part of the family isn't actually from Yorkshire afterall.

[Caliga]

Yeah, it's why I was expecting a lot more than what I got.
I wonder whether it suggests that part of the family isn't actually from Yorkshire afterall.

Entirely possible.  Our ancestors were a lot more mobile than many people realize, though obviously not as mobile as we are.

[Josquius]

I'm trying to figure out what more I can do with this.

I note there's a friends bit. Any languishers want to see how related we are?

[Caliga]

I'm trying to figure out what more I can do with this.

I note there's a friends bit. Any languishers want to see how related we are?

Sure.  PM me your email and I'll add you.

[derspiess]

I guess that only works for 23 & me?

[Caliga]

I just checked Ancestry and I don't see anything similar.  You can share family trees with people on there though.

[The Brain]

I just checked Ancestry and I don't see anything similar.  You can share family trees with people on there though.

Not necessary in Kentucky.

[Caliga]

 

[jimmy olsen]

Creepy, but very interseting.

http://www.sciencemag.org/news/2018/06/exclusive-neanderthal-minibrains-grown-dish

Exclusive: Neanderthal 'minibrains' grown in dish

By Jon CohenJun. 20, 2018 , 12:35 PM

Until now, researchers wanting to understand the Neanderthal brain and how it differed from our own had to study a void. The best insights into the neurology of our mysterious, extinct relatives came from analyzing the shape and volume of the spaces inside their fossilized skulls.

But a recent marriage of three hot fields—ancient DNA, the genome editor CRISPR, and "organoids" built from stem cells—offers a provocative, if very preliminary, new option. At least two research teams are engineering stem cells to include Neanderthal genes and growing them into "minibrains" that reflect the influence of that ancient DNA.

None of this work has been published, but Alysson Muotri, a geneticist at the University of California, San Diego (UCSD) School of Medicine, described his group's Neanderthal organoids for the first time this month at a UCSD conference called Imagination and Human Evolution. His team has coaxed stem cells endowed with Neanderthal DNA into pea-size masses that mimic the cortex, the outer layer of real brains. Compared with cortical minibrains made with typical human cells, the Neanderthal organoids have a different shape and differences in their neuronal networks, including some that may have influenced the species's ability to socialize. "We're trying to recreate Neanderthal minds," Muotri says.

Muotri focused on one of approximately 200 protein-coding genes that differ between Neanderthals and modern humans. Known as NOVA1, it plays a role in early brain development in modern humans and also is linked to autism and schizophrenia. Because it controls splicing of RNA from other genes, it likely helped produce more than 100 novel brain proteins in Neanderthals. Conveniently, just one DNA base pair differs between the Neanderthal gene and the modern human one.

Muotri and his co-workers start with skin cells from a "neurotypical person"—someone without any known genetic defects linked to neurological disorders—and manipulate their genomes to turn them into pluripotent stem cells. Using CRISPR, the team then targets NOVA1 and swaps in the Neanderthal base pair to replace the modern human one. To avoid being misled by the "off-target" DNA changes made by CRISPR as well as genetic errors that can occur from producing the stem cells, they sequence the resulting cells and discard any that have unintended mutations.

It takes several months to grow the Neanderthal DNA–containing stem cells into organoids—"We call them Neanderoids," Muotri says. Comparing them with modern human brain organoids made under identical conditions, his team found that the neuronal cells with the Neanderthalized NOVA1 migrate more quickly within an organoid as they form structures. "We think it's related to the shape of the organoid, but we have no idea what it means," says Muotri, noting that the Neanderoids have a "popcorn" shape, whereas modern human cortical organoids are spherical. The Neanderoid neurons also make fewer synaptic connections, creating what resembles an abnormal neuronal network.

Several of these differences mirror what Muotri has found studying neuronal development in the brains of children with autism. "I don't want families to conclude that I'm comparing autistic kids to Neanderthals, but it's an important observation," says Muotri, who has a stepson with autism. "In modern humans, these types of changes are linked to defects in brain development that are needed for socialization. If we believe that's one of our advantages over Neanderthals, it's relevant."

Muotri has developed the modern human brain organoids to the stage where his team can detect oscillating electrical signals within the balls of tissue. They are now wiring the organoids to robots that resemble crabs, hoping the organoids will learn to control the robots' movements. Ultimately, Muotri wants to pit them against robots run by brain Neanderoids.

"It's kind of wild," says Simon Fisher, a geneticist who heads the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who famously engineered mice to have a mutated human gene linked to speech disorders. "It's creative science."

[The Brain]

Good. Now the POTUS can get an upgrade.

[garbon]

https://www.nbcnews.com/health/health-news/drug-giant-glaxo-teams-dna-testing-company-23andme-n894531

Drug giant Glaxo teams up with DNA testing company 23andMe

Home DNA test results from the 5 million customers of 23andMe will now be used by drug giant GlaxoSmithKline to design new drugs, the two companies announced Wednesday.

It's the biggest partnership yet aimed at leveraging the increasingly popular home genetic testing market, in which customers pay for mail-in saliva tests that are analyzed by various companies. 23andMe dominates the market.

"By working with GSK, we believe we will accelerate the development of breakthroughs," 23andMe CEO Anne Wojcicki wrote in a blog post.

23andMe patrons are asked if they want to participate in scientific research. The new agreement moves this consent firmly into the field of active drug discovery research.

"As always, if our customers do not want to participate in research, they can choose to opt out at any time," Wojcicki wrote.

She emailed 23andMe customers after the announcement, including a quick link to opt out of the research.

Glaxo has invested $300 million in 23andMe and the companies have a four-year deal that gives Glaxo exclusive rights to collaborate with the DNA testing company to develop drugs.

Peter Pitts, president of the Center for Medicine in the Public Interest, said the companies should pay the 23andMe customers whose DNA is used in any research.

"Are they going to offer rebates to people who opt in so their customers aren't paying for the privilege of 23andMe working with a for-profit company in a for-profit research project?" he asked.

"It's one thing for NIH (the National institutes of Health) to ask people to donate their genome sequences for the higher good," Pitts told NBC News.

"But when two for-profit companies enter into an agreement where the jewel in the crown is your gene sequence and you are actually paying for the privilege of participating, I think that's upside-down."

Pitts also questioned whether there were solid protocols for protecting the privacy of 23andMe customers.

The first project will look at possible new drugs for treating Parkinson's disease, based on a gene called LRRK2 that is mutated in some Parkinson's patients. A study released Wednesday found that the gene may play a significant role in Parkinson's even among patients who don't have mutations.

Glaxo is already working on drugs that might work based on LRRK2 activity.

The partnership was dreamed up by the companies' two chief scientific officers: Hal Barron of Glaxo and 23andMe's Richard Scheller. The two previously worked together at another drug company, Genentech, they told CNBC.

"When you get a genetically validated target and you pursue it, it's twice as likely to end up being a medicine," Barron said in an interview on CNBC.

"The over 5 million customers that 23andMe has gained access to is really many larger ... 10 times larger, than some of the other databases out there," he added.

One of the big obstacles to genetics research is getting enough people to donate their DNA and paying to sequence it. The 23andMe database delivers a huge number of customers who have already consented and whose DNA has already been partly sequenced.

The company can go back and do more sequencing on people who have genetic variations that are of interest.

"We are also excited to leverage the patients, to have them be part of this drug discovery process," Barron said.

23andMe has been doing some of its own drug development and will now share that information with Glaxo under the agreement.

[Jacob]

Neanderthal mother, Denisovan father...

A female who died around 90,000 years ago was half Neanderthal and half Denisovan, according to genome analysis of a bone discovered in a Siberian cave. This is the first time scientists have identified an ancient individual whose parents belonged to distinct human groups. The findings were published on 22 August in Nature1.

"To find a first-generation person of mixed ancestry from these groups is absolutely extraordinary," says population geneticist Pontus Skoglund at the Francis Crick Institute in London. "It's really great science coupled with a little bit of luck."

The team, led by palaeogeneticists Viviane Slon and Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, conducted the genome analysis on a single bone fragment recovered from Denisova Cave in the Altai Mountains of Russia. This cave lends its name to the 'Denisovans', a group of extinct humans first identified on the basis of DNA sequences from the tip of a finger bone discovered2 there in 2008. The Altai region, and the cave specifically, were also home to Neanderthals.

Given the patterns of genetic variation in ancient and modern humans, scientists already knew that Denisovans and Neanderthals must have bred with each other — and with Homo sapiens (See 'Tangled Tree'). But no one had previously found the first-generation offspring from such pairings, and Pääbo says that he questioned the data when his colleagues first shared them. "I thought they must have screwed up something." Before the discovery of the Neanderthal–Denisovan individual, whom the team has affectionately named Denny, the best evidence for so close an association was found in the DNA of a Homo sapiens specimen who had a Neanderthal ancestor within the previous 4–6 generations3.

Full article here: https://www.nature.com/articles/d41586-018-06004-0

[jimmy olsen]

Really fantastic find Jacob.

Here's more about it in the Times

https://www.nytimes.com/2018/08/22/science/neanderthals-denisovans-hybrid.html

[Valmy]

So Africans are the pure-breds and the rest of us are all mutts

Well I think the notion that Euros are all part Neanderthals has been around awhile at least. But it looks like a couple of our other hominid cousins got in on that action.