Scientists at Max Delbrück Center in Berlin, the Andalusian Center for Developmental Biology (CABD) in Seville and other labs in the United States have discovered how the skate evolved these cape-like fins by peering into their DNA. They found that the key to the evolution of the skate fins lies not in the coding regions of its genome, but rather in the non-coding bits and the three-dimensional complexes that it folds into. These 3D structures are called “topologically associated domains” (TADs).

The international team describes in Nature that genomic changes that alter TADs can drive evolution. Until recently, genome evolution was mostly focused on studying variation at the DNA sequence level, but not in 3D genomic structures. “This is a new way of thinking about how genomes evolve,” says Dr. Darío Lupiáñez, geneticist at the Max Delbrück Center and one of the lead authors of the study.

“Although we found that unique gene-expression patterns establish exceptionally wide skate fins a while ago, the underlying regulatory changes in the genome have previously remained unknown,” says co-author Dr. Tetsuya Nakamura, developmental biologist at Rutgers University.

More than 450 million years ago, the genome of a primitive fish — the ancestor of all vertebrate animals — duplicated twice. The expansion in genetic material drove the rapid evolution of more than 60,000 vertebrates, including humans. One of our most distant vertebrate relativesare little skates (Leucoraja erinacea), which belong to a lineage of cartilaginous fishes that includes sharks and rays. These distant cousins are ideal organisms to learn about the evolution of traits that made us human, such as paired appendages. “Skates are cartilaginous fishes called Chondrichthyans. They are considered more similar to ancestral vertebrates,” says Dr. Christina Paliou, a developmental biologist at the CABD and one of the first authors. “We can compare the characteristics of skates with other species and determine what is novel and what is ancestral.”

An exciting time in evolutionary genomics

In 2017, the late Dr. José Luis Gómez-Skarmeta from the CABD, a founding figure in evolutionary genomics, brought together scientists from around the world to study skate evolution: laboratories with expertise in genome evolution such as the Ferdinand Marlétaz lab at University College London and Daniel Rokhsar lab at the University of California-Berkeley, in skate biology such as the Neil Shubin lab at University of Chicago, where Tetsuya Nakamura was then located (now at Rutgers) and in 3D gene regulation such as the Juan Tena at CABD, Darío Lupiáñez and Gómez-Skarmeta labs, as well as other collaborators. Gómez-Skarmeta was interested in learning how genomes evolve structurally and functionally to promote the appearance of new traits. “To a great extent, evolution is the history of changing the regulation of gene expression during development,” he said in 2018.

It was an exciting time for evolutionary genomics. Genome sequencing technologies had significantly improved and scientists could gain novel insights into how DNA, which stretches a couple of meters end-to-end, is folded into a 0.002-inch-diameter cell nucleus. “The packaging of DNA in the nucleus is far from random,” says Lupiáñez. The DNA folds into 3D structures called TADs, which contain genes and their regulatory sequences. These 3D structures ensure that the appropriate genes are switched on and off at the right time, in the right cells.

Dr. Rafael Acemel, a geneticist at the Max Delbrück Center and one of the first authors, performed experiments using the Hi-C technology, to elucidate the 3D structure of the TADs. But interpreting the results was challenging at first as the scientists needed the complete skate genome as a reference point. “At the time, the reference consisted of thousands of small unordered pieces of DNA sequence, so that did not help,” Acamel says.

To overcome this difficulty, the scientists used long-read sequencing technology, together with Hi-C data, to assemble the pieces of the DNA like a puzzle and assign the unordered sequences to skate chromosomes. With the new reference, assembling the 3D structure of the TADs using Hi-C became trivial.

They compared this improved skate genome with genomes of the closest relatives, sharks, to identify any TADs altered during skate evolution. These altered TADs included genes of the Wnt/PCP pathway, which is important for the development of fins. There was also a skate-specific variation in a non-coding sequence near the Hox genes, which also regulate fin development. “This specific sequence can activate several Hox genes in the front part of the fins, which does not happen in other fish or four-legged animals,” says Paliou. Subsequently, the scientists performed functional experiments that confirmed these molecular changes helped the skates evolve their unique fins.

TADs drive evolution

Earlier research has shown that changes in TADs can affect the expression of genes and cause diseases in humans. In this study, scientists show a role for TADs in driving evolution that has been previously noted for moles, too.

After the primitive fish ancestor duplicated its genome, many unused and redundant parts were subsequently lost. “It was not only the genes that disappeared, but also the associated regulatory elements and the TADs they are contained in,” Lupiáñez says. “I think it’s an exciting finding as it suggests that the 3D structure of the genome has an influence on its evolution.”

TADs are important for gene regulation, 40 percent of them are conserved in all vertebrates, Acemel says. “However, 60 percent of TADs have evolved in some way or another. What were the consequences of these changes for species evolution? I think that we are just scratching the surface of this exciting phenomenon,” Acemel says.

This mechanism of evolution constrained by TADs could be prevalent in nature. “We suspect that these mechanisms might explain many other interesting phenotypes that we observe in nature,” Lupiáñez says. “By adding these new layers of gene expression, gene regulation, and 3D chromatin organization, the field of evolutionary genomics is entering into a new era of discovery.”

The findings could eventually help farmers better detect, monitor and control fall armyworm populations, which negatively affect some 350 plant species — including crops like corn and cotton as well as turfgrass and other cultivated grasses.

“Nonanal is emitted by people, birds and even apples,” said Coby Schal, Blanton J. Whitmire Distinguished Professor of Entomology and co-corresponding author of a paper describing the research. “It is a universal attractant that, by itself, doesn’t have much of an effect. But when a certain percentage of nonanal is added to the multi-chemical attractant mixture discovered nearly 40 years ago, it has a highly stimulatory effect — in this case attracting male fall armyworm moths in the lab and then attracting male moths to traps in field experiments.”

Fall armyworms are found mostly in warmer climates; after originating in South America they spread to North America and then to sub-Saharan Africa, the Middle East, the Indian subcontinent, China, and, most recently, Australia. Arguably one of the world’s most devastating pests, fall armyworm caterpillars can rapidly chew through crops and lawns.

The researchers started examining ways to attract and then trap male moths as part of a “mating disruption” strategy.

“When you see fall armyworm moths you know that — two weeks later — you’re going to have caterpillars,” Schal said. “So controlling the early flying adults is key. Mating disruption is the way to go when using pheromones, as males will find traps rather than females. Pests have been eliminated from wide areas using several approaches including mating disruption — like pink bollworm, a major cotton pest in the Southwest.” Other uses of the pheromone include detection of the fall armyworm in areas not yet invaded by this pest and lure-and-kill, where the pheromone attracts the fall armyworm to an insecticide or a pathogen.

The researchers used gas chromatography, in which chemical compounds are separated in a controllable oven, to test whether the fall armyworm males would respond to other chemicals besides the known blend of chemicals. By connecting this instrument to the antennae of fall armyworm males and monitoring their electrical activity, the researchers saw that nonanal stimulated male fall armyworms.

The researchers then tested the blend with nonanal in other lab tests. Males were somewhat attracted to the traditional pheromone blend, but adding the “right amount” of nonanal to the blend greatly increased the response. The right amount turned out to be about 1% percent of the total blend, as adding too little nonanal increased the response over the traditional blend, but not by much.

Finally, the researchers used bait-and-trap experiments on NC State cotton and sorghum research fields in Raleigh and Clayton, where they tried to use different pheromone blends to capture male moths. There, they showed that nonanal by itself had no effect on males. Higher doses of nonanal in the traditional blend — at 2% and 4% concentrations — reduced the compound’s effectiveness. Again, 1% nonanal in the blend emerged as the most effective, capturing more males.

Interestingly, the shape of the trapping device also affected the success rates in capturing males. Cone-shaped traps did not perform as well as bucket-shaped traps.

The field studies also showed few other insect species — or female fall armyworms — trapped.

“We have tweaked this system to make it highly species-specific, which is especially important in places where similar moth species live,” Schal said.

The researchers filed a patent on the discovery and have exclusive licensing agreements with industry partners that will further test nonanal’s effectiveness when added to the traditional pheromone blend.

The study appears in Pest Management Science. Ahmed M. Saveer, Eduardo Hatano and Ayako Wada-Katsumata from NC State co-authored the paper, as did Robert L. Meagher from the USDA’s Agricultural Research Service. Funding was provided by a N.C. Biotechnology Center Flash Grant (2020-FLG-3809), by the USDA Southern IPM Center (2021-1645), by the U.S. National Science Foundation (NSF IOS1456973) and by the Blanton J. Whitmire Endowment at NC State.

Unlike ancient philosophers imagining the universe’s origins, modern cosmologists use quantitative tools to gain insights into the universe’s evolution and structure. Modern cosmology dates back to the early 20th century, with the development of Albert Einstein’s theory of general relativity.

Now, researchers from the Atacama Cosmology Telescope (ACT) collaboration have created a groundbreaking new image that reveals the most detailed map of dark matter distributed across a quarter of the entire sky, extending deep into the cosmos. What’s more, it confirms Einstein’s theory of how massive structures grow and bend light, over the entire 14-billion-year life span of the universe.

“We have mapped the invisible dark matter across the sky to the largest distances, and clearly see features of this invisible world that are hundreds of millions of light-years across, says Blake Sherwin, professor of cosmology at the University of Cambridge, where he leads a group of ACT researchers. “It looks just as our theories predict.”

Despite making up 85% of the universe and influencing its evolution, dark matter has been hard to detect because it doesn’t interact with light or other forms of electromagnetic radiation. As far as we know dark matter only interacts with gravity.

To track it down, the more than 160 collaborators who have built and gathered data from the National Science Foundation’s Atacama Cosmology Telescope in the high Chilean Andes observe light emanating following the dawn of the universe’s formation, the Big Bang — when the universe was only 380,000 years old. Cosmologists often refer to this diffuse light that fills our entire universe as the “baby picture of the universe,” but formally, it is known as the cosmic microwave background radiation (CMB).

The team tracks how the gravitational pull of large, heavy structures including dark matter warps the CMB on its 14-billion-year journey to us, like how a magnifying glass bends light as it passes through its lens.

“We’ve made a new mass map using distortions of light left over from the Big Bang,” says Mathew Madhavacheril, assistant professor in the Department of Physics and Astronomy at the University of Pennsylvania. “Remarkably, it provides measurements that show that both the ‘lumpiness’ of the universe, and the rate at which it is growing after 14 billion years of evolution, are just what you’d expect from our standard model of cosmology based on Einstein’s theory of gravity.”

Sherwin adds, “our results also provide new insights into an ongoing debate some have called ‘The Crisis in Cosmology,'”explaining that this crisis stems from recent measurements that use a different background light, one emitted from stars in galaxies rather than the CMB. These have produced results that suggest the dark matter was not lumpy enough under the standard model of cosmology and led to concerns that the model may be broken. However, the team’s latest results from ACT were able to precisely assess that the vast lumps seen in this image are the exact right size.

“When I first saw them, our measurements were in such good agreement with the underlying theory that it took me a moment to process the results,” says Cambridge Ph.D. student Frank Qu, part of the research team. “It will be interesting to see how this possible discrepancy between different measurements will be resolved.”

“The CMB lensing data rivals more conventional surveys of the visible light from galaxies in their ability to trace the sum of what is out there,” says Suzanne Staggs, director of ACT and Henry DeWolf Smyth Professor of Physics at Princeton University. “Together, the CMB lensing and the best optical surveys are clarifying the evolution of all the mass in the universe.”

“When we proposed this experiment in 2003, we had no idea the full extent of information that could be extracted from our telescope,” says Mark Devlin, the Reese Flower Professor of Astronomy at the University of Pennsylvania and the deputy director of ACT. “We owe this to the cleverness of the theorists, the many people who built new instruments to make our telescope more sensitive, and the new analysis techniques our team came up with.”

ACT, which operated for 15 years, was decommissioned in September 2022. Nevertheless, more papers presenting results from the final set of observations are expected to be submitted soon, and the Simons Observatory will conduct future observations at the same site, with a new telescope slated to begin operations in 2024. This new instrument will be capable of mapping the sky almost 10 times faster than ACT.

The experiment’s final report was published in Physical Review Letters in February.

Neutrinos — subatomic particles similar to an electron but that have no electric charge — are the second most abundant particles in the universe after light. However, they are some of the hardest particles to measure because they do not interact the way other particles do.

“Neutrinos have a profound impact on the universe and physics at every imaginable scale, surprising us down at the particle interaction level and having broad impact up through the cosmic scales,” said Walter Pettus, an assistant professor of physics in the IU College of Arts and Sciences. “But they are also the most frustrating to study because we know so much about them, yet we have so many gaps.”

The Majorana Demonstrator, a collaboration of 60 researchers from 24 institutions, was designed to fill many of those gaps at the same time, probing into the most fundamental properties of neutrinos.

One aspect they hoped to observe was whether the neutrino could be its own antiparticle — a subatomic particle of the same mass but with the opposite electric charge. Since the neutrino is uncharged, it is the only particle in the universe that could be its own antiparticle. Understanding that would provide insight into why the neutrino has mass in the first place — information which would have wide-spread impacts in understanding how the universe was formed.

To determine if the neutrino is its own antiparticle, the researchers needed to observe a rare occurrence called neutrinoless double-beta decay. However, this process takes a single atom at least 10²⁶ years — significantly longer than the age of the universe. Instead, they chose to observe nearly 10²⁶ atoms over the course of six years.

To observe this incredibly rare decay, the researchers needed the perfect environment. In the Sanford Underground Research Facility in the Black Hills of South Dakota, located a mile underground, they built one of the cleanest and quietest environments on Earth. Extremely sensitive detectors were made of a high-purity germanium and were packed in a 50-ton lead shield and surrounded by materials of unprecedented cleanliness. Even the copper used was grown underground in their lab with impurity levels so low they couldn’t be measured.

Pettus and a team of IU students were responsible primarily for analyzing data from the experiment. Graduate student Nafis Fuad, undergraduate senior Isaac Baker, sophomore Abby Kickbush and Jennifer James, a student with the Research Experiences for Undergraduates Program, have been involved in the project. Their focus has been on understanding the stability of the experiment, analyzing details of the recorded waveforms and characterizing backgrounds.

“It’s like looking for a tiny needle in a very, very, very big haystack — you have to carefully get rid of all the hays (a.k.a. backgrounds) possible, and you don’t even know if there’s actually a needle in there in the first place or not,” Fuad said. “It’s very exciting to be a part of that search.”

While the researchers ultimately did not observe the decay they hoped for, they did discover that the neutrino’s scale for decay is longer than the limit they placed on it, which they will test further during the next phase of the experiment. In addition, they recorded other scientific results — ranging from dark matter to quantum mechanics — that helps provide a better understanding of the universe.

Through the project, the researchers proved that the techniques they utilized could be used at a much larger scale in a potentially game-changing search that could help explain the existence of matter in the universe.

“We didn’t see the decay we were looking for, but we have raised the bar on where to look for the physics we’re going after,” Pettus said. “True to its name, the Demonstrator advanced critical technologies that we are already leveraging for the next phase of the experiment in Italy. We may not have broken our picture of physics yet, but we’ve certainly pushed the horizons, and I am very excited about what we have accomplished.”

The next phase of the project, called LEGEND-200, has already begun taking data in Italy, with plans to run over the next five years. Researchers aim to observe the decay happening at a magnitude higher sensitivity than the Majorana Demonstrator. Beyond that, thanks to support from the U.S. Department of Energy, the team is already designing the successor experiment, LEGEND-1000.

Pettus is excited about the future of this work and looks forward to involving more students on the project, both in data analysis and hardware development for LEGEND-1000.

“If we discover the neutrino is its own antiparticle, there will still be ground under our feet and stars in the sky, and our understanding of physics doesn’t change the reality of the physical laws that always have and continue to govern our universe,” Pettus said. “But knowing what’s down there at the most fundamental level and how the universe works gives us a richer, more beautiful world to live in — or possibly just weirder — and that pursuit is fundamentally human.”

The Majorana Demonstrator was managed by Oak Ridge National Laboratory for the U.S. Department of Energy Office of Nuclear Physics, with support from the National Science Foundation.