Primates show great genetic diversity that varies between species and geographic regions. “Studying this diversity is crucial also for understanding human evolution, the causes of human diseases, and for preserving our closest relatives,” says Christian Roos, a scientist in the Primate Genetics Laboratory at the German Primate Center and one of the authors. Led by researchers from Universitat Pompeu Fabra, Spain, Baylor College of Medicine, USA, and Illumina Inc, USA, the genomes of 809 individuals from 233 primate species have been sequenced. This covers nearly half of the extant primate species and increases the number of available primate genomes fourfold.

New insights into primate evolution and the uniqueness of humans

The comparative analyses provide fundamental information on the genetic diversity and evolutionary history of primates and important insights into what distinguishes humans from other primates. The genomic data have halved the number of genomic variants thought to occur exclusively in humans. “This makes it easier to look for mutations that we do not share with other primates and that could therefore be the basis for the traits that make us human,” says Dietmar Zinner, a scientist in the Cognitive Ethology Laboratory at the German Primate Center and also one of the authors. One of the studies looks more closely at baboon evolution and finds that there have been several, previously unknown episodes of hybridization and gene flow between baboon species. “We found that baboons from western Tanzania are the first nonhuman primates to have received input from three genetic lineages,” said Liye Zhang, a doctoral student at the German Primate Center and one of the lead authors of the baboon study. “These results suggest that the genetic structure of the baboon population and its history of genetic exchange between species is more complex than previously thought and show that baboons make a good model for similar processes in the evolution of early human lineages in and outside Africa,” says Dietmar Zinner.

Species conservation with the help of genome data

High genetic diversity enables species to better adapt to changing environmental conditions and pathogens. Especially in small populations, there is a risk of inbreeding and thus a reduction in genetic diversity. Already, 63 percent of all primate species are threatened with extinction, and the analysis of genetic diversity provides information which species most urgently need to be protected, at least from a genetic point of view. “We found particularly low genetic diversity in the golden snub-nosed monkey of China and the aye-aye in Madagascar,” says Christian Roos.

Rare mutations can increase disease risk

One of the limitations in human and clinical genetics is that it is currently not possible to identify among hundreds of thousands of mutations those that cause disease. To date, the genetic causes of many common diseases, such as diabetes and heart disease, are unknown, due either to a lack of genetic information or to the large number of genetic and other factors involved. By comparing the primate genomes, 4.3 million mutations have now been identified that may alter protein function and thus lead to disease in humans. Six percent of the 4.3 million mutations identified are, however, common in primates and are therefore considered to potentially have little impact on human disease because they are tolerated in these animals. Thanks to the PrimateAI-3D deep-learning algorithm developed by Illumina Inc, disease-causing mutations can now be better identified. “It’s a kind of ChatGPT for genetics that uses genome sequences instead of human language,” explains Kyle Farh, vice director of the AI group at Illumina Inc, the global leader in DNA sequencing.

In the early 1980s, Northwestern University’s Farhad Yusef-Zadeh discovered gigantic, one-dimensional filaments dangling vertically near Sagittarius A*, our galaxy’s central supermassive black hole. Now, Yusef-Zadeh and his collaborators have discovered a new population of filaments — but these threads are much shorter and lie horizontally or radially, spreading out like spokes on a wheel from the black hole.

Although the two populations of filaments share several similarities, Yusef-Zadeh assumes they have different origins. While the vertical filaments sweep through the galaxy, towering up to 150 light-years high, the horizontal filaments look more like the dots and dashes of Morse code, punctuating only one side of Sagittarius A*.

The study will be published on Friday (June 2) in The Astrophysical Journal Letters.

“It was a surprise to suddenly find a new population of structures that seem to be pointing in the direction of the black hole,” Yusef-Zadeh said. “I was actually stunned when I saw these. We had to do a lot of work to establish that we weren’t fooling ourselves. And we found that these filaments are not random but appear to be tied to the outflow of our black hole. By studying them, we could learn more about the black hole’s spin and accretion disk orientation. It is satisfying when one finds order in a middle of a chaotic field of the nucleus of our galaxy.”

An expert in radio astronomy, Yusef-Zadeh is a professor of physics and astronomy at Northwestern’s Weinberg College of Arts and Sciences and member of CIERA.

Decades in the making

The new discovery may come as a surprise, but Yusef-Zadeh is no stranger to uncovering mysteries at the center of our galaxy, located 25,000 light-years from Earth. The latest study builds on four decades of his research. After first discovering the vertical filaments in 1984 with Mark Morris and Don Chance, Yusef-Zadeh along with Ian Heywood and their collaborators later uncovered two gigantic radio-emitting bubbles near Sagittarius A*. Then, in a series of publications in 2022, Yusef-Zadeh (in collaborations with Heywood, Richard Arent and Mark Wardle) revealed nearly 1,000 vertical filaments, which appeared in pairs and clusters, often stacked equally spaced or side by side like strings on a harp.

Yusef-Zadeh credits the flood of new discoveries to enhanced radio astronomy technology, particularly the South African Radio Astronomy Observatory’s (SARAO) MeerKAT telescope. To pinpoint the filaments, Yusef-Zadeh’s team used a technique to remove the background and smooth the noise from MeerKAT images in order to isolate the filaments from surrounding structures.

“The new MeerKAT observations have been a game changer,” he said. “The advancement of technology and dedicated observing time have given us new information. It’s really a technical achievement from radio astronomers.”

Horizontal vs. vertical

After studying the vertical filaments for decades, Yusef-Zadeh was shocked to uncover their horizontal counterparts, which he estimates are about 6 million years old. “We have always been thinking about vertical filaments and their origin,” he said. “I’m used to them being vertical. I never considered there might be others along the plane.”

While both populations comprise one-dimensional filaments that can be viewed with radio waves and appear to be tied to activities in the galactic center, the similarities end there.

The vertical filaments are perpendicular to the galactic plane; the horizontal filaments are parallel to the plane but point radially toward the center of the galaxy where the black hole lies. The vertical filaments are magnetic and relativistic; the horizontal filaments appear to emit thermal radiation. The vertical filaments encompass particles moving at speeds near the speed of light; the horizontal filaments appear to accelerate thermal material in a molecular cloud. There are several hundred vertical filaments and just a few hundred horizontal filaments. And the vertical filaments, which measure up to 150 light-years high, far surpass the size of the horizontal filaments, which measure just 5 to 10 light-years in length. The vertical filaments also adorn space around the nucleus of the galaxy; the horizontal filaments appear to spread out to only one side, pointing toward the black hole.

“One of the most important implications of radial outflow that we have detected is the orientation of the accretion disk and the jet-driven outflow from Sagittarius A* along the galactic plane,” Yusef-Zadeh said.

‘Our work is never complete’

The new discovery is filled with unknowns, and Yusef-Zadeh’s work to unravel its mysteries has just begun. For now, he can only consider a plausible explanation about the new population’s mechanisms and origins.

“We think they must have originated with some kind of outflow from an activity that happened a few million years ago,” Yusef-Zadeh said. “It seems to be the result of an interaction of that outflowing material with objects near it. Our work is never complete. We always need to make new observations and continually challenge our ideas and tighten up our analysis.”

The study, “The population of the galactic center filaments: Position angle distribution reveal a degree-scale collimated outflow from Sgr A* along the galactic plane,” was supported by NASA (award number 80GSFC21M0002). The SARAO is a facility of the National Research Foundation, an agency of the Department of Science and Innovation.

The RNA fragments are from viruses that infected the symbionts as long ago as 160 million years. The discovery is described in an open-access study published this week in the Nature journal Communications Biology, and it could help scientists understand how corals and their partners fight off viral infections today. But it was a surprising find because most RNA viruses are not known for embedding themselves in the DNA of organisms they infect.

The research showed that endogenous viral elements, or EVEs, appear widely in the genomes of coral symbionts. Known as dinoflagellates, the single-celled algae live inside corals and provide them with their dramatic colors. The EVE discovery underscores recent observations that viruses other than retroviruses can integrate fragments of their genetic code into their hosts’ genomes.

“So why did it get in there?” asked study co-author Adrienne Correa of Rice University. “It could just be an accident, but people are starting to find that these ‘accidents’ are more frequent than scientists had previously believed, and they’ve been found across all kinds of hosts, from bats to ants to plants to algae.”

That an RNA virus appears at all in coral symbionts was also a surprise.

“This is what made this project so interesting to me,” said study lead author Alex Veglia, a graduate student in Correa’s research group. “There’s really no reason, based on what we know, for this virus to be in the symbionts’ genome.”

The study was supported by the Tara Ocean Foundation and the National Science Foundation and led by Correa, Veglia and two scientists from Oregon State University, postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. The research provides clues that can help scientists better understand the ecological and economic impact of viruses on reef health.

The researchers did not find EVEs from RNA viruses in samples of filtered seawater or in the genomes of dinoflagellate-free stony corals, hydrocorals or jellyfish. But EVEs were pervasive in coral symbionts that were collected from dozens of coral reef sites, meaning the pathogenic viruses were — and probably remain — picky about their target hosts.

“There’s a huge diversity of viruses on the planet,” said Correa, an assistant professor of biosciences. “Some we know a lot about, but most viruses haven’t been characterized. We might be able to detect them, but we don’t know who serves as their hosts.”

She said viruses, including retroviruses, have many ways to replicate by infecting hosts. “One reason our study is cool is because this RNA virus is not a retrovirus,” Correa said. “Given that, you wouldn’t expect it to integrate into host DNA.

“For quite a few years, we’ve seen a ton of viruses in coral colonies, but it’s been hard to tell for sure what they were infecting,” Correa said. “So this is likely the best, most concrete information we have for the actual host of a coral colony-associated virus. Now we can start asking why the symbiont keeps that DNA, or part of the genome. Why wasn’t it lost a long time ago?”

The discovery that the EVEs have been conserved for millions of years suggests they may somehow be beneficial to the coral symbionts and that there is some kind of mechanism that drives the genomic integration of the EVEs.

“There are a lot of avenues we can pursue next, like whether these elements are being used for antiviral mechanisms within dinoflagellates, and how they are likely to affect reef health, especially as oceans warm,” Veglia said.

“If we’re dealing with an increase in the temperature of seawater, is it more likely that Symbiodiniaceae species will contain this endogenous viral element? Does having EVEs in their genomes improve their odds of fighting off infections from contemporary RNA viruses?” he said.

“In another paper, we showed there was an increase in RNA viral infections when corals underwent thermal stress. So there are a lot of moving parts. And this is another good piece of that puzzle.”

Correa said, “We can’t assume that this virus has a negative effect. But at the same time, it does look like it’s becoming more productive under these temperature stress conditions.”

Thurber is the Emile F. Pernot Distinguished Professor in Oregon State’s Department of Microbiology.

The study included more than 20 co-authors from the University of Konstanz, Germany; the Institute of Microbiology and Swiss Institute of Bioinformatics, Zürich; the University of Perpignan, France; the Scientific Center of Monaco; the Université Paris-Saclay, Evry, France; the Tara Ocean Foundation, Paris; the University of Maine; Sorbonne University, France; the University of Tsukuba, Japan; Paris Science and Letters University, France; the University of Paris-Saclay; the Weizmann Institute of Science, Rehovot, Israel; Côte d’Azur University, Nice, France; the European Bioinformatics Institute, University of Cambridge, England; Ohio State University; and the National University of Ireland, Galway.

National Science Foundation support was provided by three grants (2145472, 2025457, 1907184).

The three-year study found that a daily drop in each eye of a low dose of atropine, a drug used to dilate pupils, was better than a placebo at limiting eyeglass prescription changes and inhibiting elongation of the eye in nearsighted children aged 6 to 10.

That elongation leads to myopia, or nearsightedness, which starts in young kids and continues to get worse into the teen years before leveling off in most people. In addition to requiring life-long vision correction, nearsightedness increases the risk for retinal detachment, macular degeneration, cataracts and glaucoma later in life — and most corrective lenses don’t do anything to stop myopia progression.

“The idea of keeping eyeballs smaller isn’t just so people’s glasses are thinner — it would also be so that in their 70s they don’t suffer visual impairment,” said lead study author Karla Zadnik, professor and dean of the College of Optometry at The Ohio State University.

“This is exciting work for the myopia research community, which I’ve been part of for 35 years. We’ve talked about treatment and control for decades,” she said. “And it’s exciting to think that there could be options in the future for millions of children we know are going to be myopic.”

The results of the CHAMP (Childhood Atropine for Myopia Progression) trial are published today (June 1, 2023) in JAMA Ophthalmology.

About one in three adults worldwide is nearsighted, and the global prevalence of myopia is predicted to increase to 50% by 2050. Though one federally approved contact lens can slow progression of nearsightedness, no pharmaceutical products are approved in the United States or Europe to treat myopia.

Animal studies years ago hinted at atropine’s ability to slow the growth of the eye, but the full-strength drug’s interference with near vision and concerns about pupil dilation hindered early considerations of its potential as a human therapy for myopia. More recent research has suggested a low dose of atropine might be the ticket.

This new double-masked, randomized phase 3 trial assessed the safety and effectiveness of two low-dose solutions, with atropine concentrations of either .01% or .02%, versus placebo. Treatment for each of the 489 children aged 6 to 10 assessed for the drug’s effectiveness consisted of one daily drop per eye at bedtime, which minimized the disruption of any blurring effects atropine might have on vision.

Researchers were a bit surprised to find that the most significant improvements at all time points compared to placebo resulted from the solution containing .01% of atropine. Though the .02% atropine formulation was also better at slowing progression of myopia than placebo, the results were less consistent.

“The .01% story is clearer and more obvious in terms of significantly slowing both the growth of the eye as well as then resulting in a lower glasses prescription,” Zadnik said.

Including a measure of the eye’s growth was a key component of the study because “the field is actually moving toward axial elongation being as important as, or more important than, the glasses prescription in terms of the most meaningful outcome,” she said. “If we’re trying to slow eye growth to prevent bad outcomes for people in their 80s, measuring the eye growth directly is really important.”

The drugs’ safety was assessed in a larger sample of 573 participants that also included children as young as 3 and up to age 16. Both low-dose formulations were safe and well tolerated. The most common side effects were sensitivity to light, allergic conjunctivitis, eye irritation, dilated pupils and blurred vision, although reports of these side effects were few.

The CHAMP trial was the first study of low-dose atropine to include placebo controls for three years and to involve a large, diverse population recruited from 26 clinical sites in North America and five countries in Europe. In a second section of the trial, researchers are evaluating how the eyes respond when the treatment is over.

The experimental drug is made without preservatives and, if federally approved as a therapy, would be distributed in single-use packaging for convenience and to prevent contamination. Off-label low-dose atropine that can currently be obtained at compounding pharmacies may contain preservatives that can lead to dry eye and corneal irritation, researchers noted.

The experimental product studied in the CHAMP trial is manufactured by Vyluma, a New Jersey development-stage biopharmaceutical company with a focus on pharmaceutical treatments for refractive errors of the eye. A subsidiary of Nevakar Inc., Vyluma sponsored the trial, has submitted a New Drug Application to the FDA to seek approval in the U.S. and has partnered with two companies to commercialize the product outside the United States..

Zadnik led the study as a paid expert consultant to Vyluma. Jennifer Fogt, assistant professor at Ohio State, also worked on the trial. Additional co-authors Erica Schulman of SUNY College of Optometry; Ian Flitcroft of the Center for Eye Research in Dublin, Ireland; Louis Blumenfeld of Eye Physicians of Central Florida; and Tung Fong, Eric Lang, Houman Hemmati and Simon Chandler of Vyluma represented the CHAMP trial group investigators.