Category Archives: Transhuman News

Scientists have found that a "ghost" lineage of archaic human may have interbred with the ancestors of modern humans in what is now sub-Saharan Africa around 200,000 years ago.

A protein that helps make human spit slimy reveals signs that the ancestors of modern humans interbred with an extinct human lineage that was an even more distant relation than Neanderthals, a new study finds.

The ancestors of modern humans once shared the world with ancient human lineages such as the Neanderthals, the closest extinct relatives of modern humans, as well as the Denisovans, which might have once roamed a vast range stretching from Siberia to Southeast Asia. In previous research, DNA extracted from fossilized bones and teeth of Neanderthalsand Denisovanshas revealed that the ancestors of modern humans interbred with both of these groups.

Previous research also suggested that the ancestors of modern humans may have interbred with other human lineages not known from the fossil record. For example, a 2011 studyanalyzing modern human DNA found that the species may have bred with a now-extinct lineage of humanity before leaving Africa. [Denisovan Gallery: Tracing the Genetics of Human Ancestors]

Now, researchers suggest that a "ghost" lineage of ancient humans may have contributed the DNA for a protein called mucin-7 found in the saliva of modern humansliving in sub-Saharan Africa today.

"About 5 to 7 percent of every population in sub-Saharan Africa has this divergent protein," said Omer Gokcumen, study co-senior author of the new study and an evolutionary genomicist at the University at Buffalo in New York.

The scientists were investigating mucin-7 in order to learn more about its role in human health. This molecule helps give saliva its slimy consistency and binds onto microbes, potentially helping rid the body of dangerous germs.

The researchers examined copies of the gene for mucin-7 the gene is called MUC7 in more than 2,500 modern human genomes. The scientists found that a number of genomes from sub-Saharan Africa possessed a version of the MUC7 gene that was wildly different from versions found in other modern humans. In fact, the Neanderthal and Denisovan versions of this gene more closely resembled those of other modern humans than this outlier did.

The researchers suggested the most plausible explanation for this mysterious version of the MUC7 gene is that it came from what they called a "ghost" lineage that is, one that scientists have not found the fossils of yet.

"We were not looking for this discovery we essentially stumbled onto it," Gokcumen told Live Science.

That this variant is so widespread across Africa suggests that it may have entered the modern human gene pool before the ancestors of modern humans separatedinto different regions across that continent, Gokcumen said. Given the usual rate at which genes mutate during the course of time, the researchers estimated the interbreeding event with this mystery lineage "may have happened about 200,000 years ago, but this lineage separated from the ancestors of modern humans maybe 500,000 years or 1 million years ago," Gokcumen added.

The scientists said they aren't sure how the variants of this protein might differ in function. "We do know that MUC7 has two major functions," said study co-senior author Stefan Ruhl, an oral biologist also at the University at Buffalo. "One is helping to lubricate the oral cavity for eating and swallowing, and the other, and this may be more important, is to let good microbes stay in the body and sort out the undesirable ones."

An analysis of mouth, skin, stool and other biological samples from 130 people revealed that different versions of MUC7 were strongly associated with different oral microbiomes the collections of microbes within the mouth. "This suggests that MUC7 is interacting with the oral microbiome and plays a role in terms of viruses, bacteria, parasites or fungi," Ruhl told Live Science. "On the other hand, we haven't ruled out that it may play a role in lubrication say, when it comes to environmental conditions such as dryness of the air."

Future research can explore when and where this interbreeding happened, "and if it happened just once or multiple times," Gokcumen said.

The scientists detailed their findingsonline July 21 in the journal Molecular Biology and Evolution.

Original article on Live Science.

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Human Ancestor Mated with 'Ghost Lineage' And the Proof Is in Your Spit - Live Science

Terence Capellini, an associate professor of human evolutionary biology, is co-author of new research revealing a genetic switch that changes the activity of a key skeletal gene related to height, and pinpoints a variant in the switch that favors shortness and is far more prevalent among Eurasian populations than expected.

The study, described in a July 3 paper in Nature Genetics, also points to a surprising link between the sequence that favors shortness and an increased risk of osteoarthritis.

There are a couple [of] aspects of this study that are interesting, Capellini said. One is that these genetic variants are occurring in noncoding sequences, so while genes are important, this shows that the genetic machinery around a gene can have a dramatic impact on how it works. But another interesting finding is that while evolution has increased the frequency of a variant that leads to decreased height, because of linked mutations, there is also an increased risk of osteoarthritis.

From the outset, the goal of Capellini and his colleagues wasnt to understand that link, but simply to better understand the genetics behind height variation.

To do so, the team from Harvard, Stanford, and the University of Waterloo in Ontario, Canada, combined the power of developmental biology, evolutionary genomics, and bioinformatics. The gene they chose to focus on, GDF5, has been linked repeatedly to height variation in genome-wide association studies.

This type of study has been done on upwards of 250,000 people, Capellini said. When you look at the results of these studies, this gene comes up again and again, and when you zoom in on the GDF5 region there are a lot of genetic variants that are also associated with height variation.

Essentially, Capellini said, those variations found in the noncoding regions around the gene can alter the activity of the gene in various areas in the body if they occur in specific genetic switches.

If you want to influence height, one place you want to turn on the gene is in the growth plates of bones, Capellini said. But the reality is that, for all the height studies that have been done, no one really knows the switches, let alone which one in the GDF5 region contains the actual DNA variant that causes the change in height.

To find it, the researchers attached a blue-producing reporter gene to each potential switch, and then tracked where the color was expressed in mouse embryos. What they found, he said, was a sequence that controls the activity of the gene in the growth plates, and, more importantly, a single DNA base change in the switch that influences its activity and height variation.

When Capellini and colleagues deleted the GDF5 growth plate switch from mice, their bones became shorter. This was in line with what the researchers saw when testing the human short height variant. Interestingly, they also saw that the femoral neck the connection between the femur and the femoral head grew shorter as well.

Other tests showed that the variant in favor of shorter height is prevalent among European and Asian populations, but rarely seen among African populations. Capellini and his colleagues suggest that this may be due to several factors:

We argue that shorter height may have been advantageous in the past because if you were living in a colder climate, having a short, stocky body may actually help you survive, he said. When you look at animals that reside in the Arctic, they tend to have shorter appendages to reduce the risk of frostbite and to maintain body heat.

However, given the effect of the switch on femoral neck length, Capellini and Stanfords David Kingsley also suggest, If youre tall and you have a long femoral neck, youre at higher risk for hip fracture So the thinking is that a shorter femoral neck might also have been a protective mechanism thats brought this sequence to very high frequency in some populations.

Its a very interesting situation, because favorable selection during human history means the variant we are studying is now present in literally billions of people, said Kingsley, a professor of developmental biology and co-leader of the study.

The growth switch wasnt the only one Capellini, Kingsley, and colleagues found.

The variant that decreases height is lowering the activity of GDF5 in the growth plates, but there are lots of other mutations that are physically linked to it, Capellini said. A few others occur in different switches we found, each of which turn GDF5 on in the joints, and these mutations are associated with hip and knee osteoarthritis risk, and likely lower GDF5 activity in the joints.

While the study offers new insight into the roles of noncoding DNA and the complex relationship between height and arthritis, Capellini stressed that GDF5 is only one gene of many that play a role in height, and that more work needs to be done to get a fuller picture.

We know the genetics of height and arthritis are complex, with potentially thousands of genes involved, he said. This makes us appreciate that biology is highly complex and we need to tease out more of these relationships to really get a sense of how one feature may be associated with another.

The research was supported with funding from the Natural Sciences and Engineering Research Councilof Canada, the Arthritis Foundation, the National Institutes of Health, the William F. Milton Fund of Harvard, the China Scholarship Council, and the Jason S. Bailey Fund of Harvard.

See the original post:
New insight on height, arthritis - Harvard Gazette

Dive Brief:

Just two quarters after taking over as CEO at Biogen, Michel Vounatsos says he intends to make the company the "fastest-growing large-cap biotech."The new exec hopes to diversify Biogen's pipeline beyond the current MS franchise and the Alzheimers disease candidate aducanumab, which currently represents its largest pipeline opportunity or risk, if it should fail.

During an earnings call on July 25, Biogen laid out a plan to shift resources back to its base neuroscience franchise; something it moved away from for several years under previous CEO George Scangos.

Biogen intends to redirect about $400 million annually by 2019 toward R&D and "commercial value creation opportunities,"by "unlocking resources"within the portfolio.

"We believe our strategy will help support a healthy, resilient MS business for Biogen,"said Vounatsos, who also touted the overall performance of its new SMA drug Spinraza and highlighting its value to the company.

"Overall, we believe Spinraza will become one of our largest commercial assets, shifting the center of gravity for Biogen beyond MS to generate new growth,"he added.

On the call, Biogen execs said Spinraza will be a model for the types of drugs and deals the company wants to pursue. (Spinraza was developed through a deal with Ionis.)

Vounatsos also cited a recent deal with Bristol-Myers Squibb as the type of "growth-driving"deal that the company wants to replicate.In April, Biogen picked up a Phase 2-ready drug for Alzheimers disease and progressive supranuclear palsy from Bristol-Myers for $300 million upfront and the promise of $410 million in milestones.

While the company intends to retain its leadership position in MS, it hopes to move into other areas of neuroscience through both R&D and business development.

"We plan to maximize our performance in the near-term, while focusing on growth in the future,"said Vounatsos, who pointed to four key areas including MS, Alzheimers disease, Parkinsons disease and SMA. He also noted that pain, ophthalmology, neuropsychiatry and acute neurology would be tangential areas of interest.

"Biogen has a long history in neurology and has built up substantial core competencies in the area. It is our belief that no other area of medicine holds as much promise, with as much need, as neuroscience,"said EVP of R&D Mike Ehlers on the call.

"The opportunity space is vast and the time is right. With an ongoing revolution in basic neurobiology, human genetics, biomarkers, patient stratification and neural imaging, as well as increasing receptivity to clinical endpoints and regulatory paths, we believe that all signs point to neuroscience as the next oncology. Yet, for most companies, it is either not an area of focus or represents an opportunistic play. Our view is that success in neuroscience requires intense focus and that opportunistic approaches will not maximize value. There is a need for a leader in neuroscience. Our goal is to be that leader,"he added.

Top image credit: Dollar Photo Club

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Biogen: 'Our goal is to be that leader' - BioPharma Dive