One of the challenges of working with ancient DNA samples is that damage accumulates over time, breaking up the structure of the double helix into ever smaller fragments. In the samples we’ve worked with, these fragments scatter and mix with contaminants, making reconstructing a genome a large technical challenge.
But a dramatic paper released on Thursday shows that this isn’t always true. Damage does create progressively smaller fragments of DNA over time. But, if they’re trapped in the right sort of material, they’ll stay right where they are, essentially preserving some key features of ancient chromosomes even as the underlying DNA decays. Researchers have now used that to detail the chromosome structure of mammoths, with some implications for how these mammals regulated some key genes.
DNA meets Hi-C
The backbone of DNA’s double helix consists of alternating sugars and phosphates, chemically linked together (the bases of DNA are chemically linked to these sugars). Damage from things like radiation can break these chemical linkages, with fragmentation increasing over time. When samples reach the age of something like a Neanderthal, very few fragments are longer than 100 base pairs. Since chromosomes are millions of base pairs long, it was thought that this would inevitably destroy their structure, as many of the fragments would simply diffuse away.
But that will only be true if the medium they’re in allows diffusion. And some scientists suspected that permafrost, which preserves the tissue of some now-extinct Arctic animals, might block that diffusion. So, they set out to test this using mammoth tissues, obtained from a sample termed YakInf that’s roughly 50,000 years old.
The challenge is that the molecular techniques we use to probe chromosomes take place in liquid solutions, where fragments would just drift away from each other in any case. So, the team focused on an approach termed Hi-C, which specifically preserves information about which bits of DNA were close to each other. It does this by exposing chromosomes to a chemical that will link any pieces of DNA that are close physical proximity. So, even if those pieces are fragments, they’ll be stuck to each other by the time they end up in a liquid solution.
A few enzymes are then used to convert these linked molecules to a single piece of DNA, which is then sequenced. This data, which will contain sequence information from two different parts of the genome, then tells us that those parts were once close to each other inside a cell.
Interpreting Hi-C
On its own, a single bit of data like this isn’t especially interesting; two bits of genome might end up next to each other at random. But when you have millions of bits of data like this, you can start to construct a map of how the genome is structured.
There are two basic rules governing the pattern of interactions we’d expect to see. The first is that interactions within a chromosome are going to be more common than interactions between two chromosomes. And, within a chromosome, parts that are physically closer to each other on the molecule are more likely to interact than those that are farther apart.
So, if you are looking at a specific segment of, say, chromosome 12, most of the locations Hi-C will find it interacting with will also be on chromosome 12. And the frequency of interactions will go up as you move to sequences that are ever closer to the one you’re interested in.
On its own, you can use Hi-C to help reconstruct a chromosome even if you start with nothing but fragments. But the exceptions to the expected pattern also tell us things about biology. For example, genes that are active tend to be on loops of DNA, with the two ends of the loop held together by proteins; the same is true for inactive genes. Interactions within these loops tend to be more frequent than interactions between them, subtly altering the frequency with which two fragments end up linked together during Hi-C.
Ah, cats. We love our furry feline overlords despite the occasional hairball and their propensity to scratch the furniture to sharpen their claws. The latter is perfectly natural kitty behavior, but overly aggressive scratching is usually perceived as a behavioral problem. Veterinarians frown on taking extreme measures like declawing or even euthanizing such “problematic” cats. But there are alternative science-backed strategies for reducing or redirecting the scratching behavior, according to the authors of a new paper published in the journal Frontiers in Veterinary Science.
This latest study builds on the group’s prior research investigating the effects of synthetic feline facial pheromones on undesirable scratching in cats, according to co-author Yasemin Salgirli Demirbas, a veterinary researcher at Ankara University in Turkey. “From the beginning, our research team agreed that it was essential to explore broader factors that might exacerbate this issue, such as those influencing stress and, consequently, scratching behavior in cats,” she told Ars. “What’s new in this study is our focus on the individual, environmental, and social dynamics affecting the level of scratching behavior. This perspective aims to enhance our understanding of how human and animal welfare are interconnected in different scenarios.”
The study investigated the behavior of 1,211 cats, with data collected via an online questionnaire completed by the cats’ caregivers. The first section collected information about the caregivers, while the second asked about the cats’ daily routines, social interactions, environments, behaviors, and temperaments. The third and final section gathered information about the frequency and intensity of undesirable scratching behavior in the cats based on a helpful “scratching index.”
The team concluded that there are several factors that influence the scratching behavior of cats, including environmental factors, high levels of certain kinds of play, and increased nocturnal activity. But stress seems to be the leading driver. “Cats might scratch more as a way to relieve stress or mark their territory, especially if they feel threatened or insecure,” said Demirbas. And the top source of such stress, the study found, is the presence of small children in the home.
Florida carpenter ants (Camponotus floridanus) selectively treat the wounded limbs of their fellow ants, according to a new paper published in the journal Current Biology. Depending on the location of the injury, the ants either lick the wounds to clean them or chew off the affected limb to keep infection from spreading. The treatment is surprisingly effective, with survival rates of around 90–95 percent for amputee ants.
“When we’re talking about amputation behavior, this is literally the only case in which a sophisticated and systematic amputation of an individual by another member of its species occurs in the animal kingdom,” said co-author Erik Frank, a behavioral ecologist at the University of Würzburg in Germany. “The fact that the ants are able to diagnose a wound, see if it’s infected or sterile, and treat it accordingly over long periods of time by other individuals—the only medical system that can rival that would be the human one.”
Frank has been studying various species of ants for many years. Late last year, he co-authored a paper detailing how Matabele ants (Megaponera analis) south of the Sahara can tell if an injured comrade’s wound is infected or not, thanks to chemical changes in the hydrocarbon profile of the ant cuticle when a wound gets infected. These ants only eat termites, but termites have powerful jaws and use them to defend against predators, so there is a high risk of injury to hunting ants.
If an infected wound is identified, the ants then treat said wound with antibiotics produced by a special gland on the side of the thorax (the metapleural gland). Those secretions are made of some 112 components, half of which have antimicrobial properties. Frank et al.’s experiments showed that applying these secretions reduced the mortality rate of injured ants by 90 percent, and future research could lead to the discovery of new antibiotics suitable for treating humans. (This work was featured in an episode of a recent Netflix nature documentary, Life on Our Planet.)
Those findings caused Frank to ponder if the Matabele ant is unique in its ability to detect and treat infected wounds, so he turned his attention to the Florida carpenter ant. These reddish-brown ants nest in rotting wood and can be fiercely territorial, defending their homes from rival ant colonies. That combat comes with a high risk of injury. Florida carpenter ants lack a metapleural gland, however, so Frank et al. wondered how this species treats injured comrades. They conducted a series of experiments to find out.
Frank et al. drew their subjects from colonies of lab-raised ants (produced by queens collected during 2017 fieldwork in Florida), and ants targeted for injury were color-tagged with acrylic paint two days before each experiment. Selective injuries to tiny (ankle-like) tibias and femurs (thighs) were made with sterile Dowel-scissors, and cultivated strains of P. aeruginosa were used to infect some of those wounds, while others were left uninfected as a control. The team captured the subsequent treatment behavior of the other ants on video and subsequently analyzed that footage. They also took CT scans of the ants’ legs to learn more about the anatomical structure.
Ultra-athlete Ross Edgley is no stranger to pushing his body to extremes. He once ran a marathon while pulling a one-ton car; ran a triathlon while carrying a 100-pound tree; and climbed a 65-foot rope over and over again until he’d climbed the equivalent of Mt. Everest—all for charity. In 2016, he set the world record for the world’s longest staged sea swim around the coastline of Great Britain: 1780 miles over 157 days.
At one point during that swim, a basking shark appeared and swam alongside Edgley for a day and a half. That experience ignited his curiosity about sharks and eventually led to his new National Geographic documentary, Shark vs. Ross Edgley—part of four full weeks of 2024 SHARKFEST programming. Edgley matches his athletic prowess against four different species of shark. He tries to jump out of the water (polaris) like a great white shark; withstand the G forces produced by a hammerhead shark‘s fast, rapid turns; mimic the extreme fasting and feasting regimen of a migrating tiger shark; and match the swimming speed of a mako shark.
“I love this idea of having a goal and then reverse engineering and deconstructing it,” Edgley told Ars. “[Sharks are] the ultimate ocean athletes. We just had this idea: what if you’re crazy enough to try and follow in the footsteps of four amazing sharks? It’s an impossible task. You’re going to fail, you’re going to be humbled. But in the process, we could use it as a sports/shark science experiment, almost like a Trojan horse to bring science and ocean conservation to a new audience.”
And who better than Edgley to take on that impossible challenge? “The enthusiasm he brings to everything is really infectious,” marine biologist and shark expert Mike Heithaus of Florida International University told Ars. “He’s game to try anything. He’d never been in the water with sharks and we’re throwing him straight in with big tiger sharks and hammerheads. He’s loving the whole thing and just devoured all the information.”
That Edgley physique doesn’t maintain itself, so the athlete was up at 4 AM swimming laps and working out every morning before the rest of the crew had their coffee. “I’m doing bicep curls with my coffee cup and he’s doing bicep curls with the 60-pound underwater camera,” Heithaus recalled. “For the record, I got one rep in and I’m very proud of that.” Score one for the shark expert.
(Spoilers below for the various shark challenges.)
Ross vs. the great white shark
For the first challenge, Edgley took on the great white shark, a creature he describes as a “submarine with teeth.” These sharks are ambush hunters, capable of propelling their massive bodies fully out of the water in an arching leap. That maneuver is called a polaris, and it’s essential to the great white shark’s survival. It helps that the shark has 65 percent muscle mass, particularly concentrated in the tail, as well as a light skeleton and a large liver that serves as buoyancy device.
Edgley, by comparison, is roughly 45 percent muscle mass—much higher than the average human but falling short of the great white shark. To help him try to match the great white’s powerful polaris maneuver, Edgley sought tips on biomechanics from the Aquabatix synchronized swim team, since synchronized swimmers must frequently launch their bodies fully out of the water during routines. They typically get a boost from their teammates to do so.
The team did manage to boost Edgley out of the water, but sharks don’t need a boost. Edgley opted to work with a monofin, frequently used in underwater sports like free diving or finswimming, to see what he could achieve on his own power. After a bit of practice, he succeeded in launching 75 percent of his body (compared to the shark’s 100 percent) out of the water. Verdict: Edgley is 75 percent great white shark.
Ross vs. the hammerhead shark
Next up: Edgley pitted himself against the remarkable underwater agility of a hammerhead shark. Hammerheads are known for being able to swim fast and turn on a dime, thanks to a flexible skeleton that enables them to bend and contort their bodies nearly in half. They’re able to withstand some impressive G forces (up to 3 G’s) in the process. According to Heithaus, these sharks feed on other rays and other sharks, so they need to be built for speed and agility—hence their ability to accelerate and turn rapidly.
The NatGeo crew captured impressive underwater footage of the hammerheads in action, including Edgley meeting a 14.7 hammerhead named “Queenie”—one of the largest great hammerheads that visits Bimini in the Bahamas during the winter. That footage also includes shots of divers feeding fish to some of the hammerheads by hand. “They know every shark by name and the sharks know the feeders,” said Heithaus. “So you can safely get close to these big amazing creatures.”
For years, scientists had wondered about the purpose of the distinctive hammer-shaped head. It may help them scan a larger area of the ocean floor while hunting. Like all sharks, hammerheads have sensory pores called ampullae of Lorenzini that allow them to detect electrical signals and hence possible prey. The hammer-shaped head distributes those pores over a wider span.
But according to Heithaus, the hammer shape also operates a bit like the big broad flap of an airplane wing, resulting in excellent hydrodynamics. Moving at high speeds, “You can just tilt the head a tiny bit and bank a huge degree,” he said. “So if a ray turns 180 degrees to escape, the hammerhead can track with it. Other species would take a wider turn and fall behind.”
The airplane wing analogy gave Edgley an idea for how he could mimic the tight turns and high G forces of a hammerhead shark: take a flight in a small stunt plane. The catch: Edgley is not a fan of flying. And as he’d feared, he became horribly airsick during the challenge, even puking into a little airbag at one point. “It looks so cool in the clip,” he said. “But at the time, I was in a world of trouble.” Pilot Mark Greenfield finally cut the experiment short when he determined that Edgley was too sick to continue. Verdict: Edgley is 0 percent hammerhead shark.
Ross vs. the tiger shark
The third challenge was trying to match the fortitude of a migrating tiger shark as it makes its way over thousands of miles without food, only feasting at journey’s end. “I was trying to understand the psychology of a tiger shark because there’s just nothing for them to eat [on the journey],” said Ross. And once they arrive at their destination, “they can chow down on entire whale carcasses and eat just about anything. That idea of feast and famine is something we humans used to do all the time. We live quite comfortably now so we’ve lost touch with that.”
The first step was to figure out just how many calories a migrating tiger shark can consume in a single bite. Heithaus has been part of SHARKFEST for several years now and recalled one throwback show, Sharks vs. Dolphins, in which he tried to determine which species of of shark were attacking dolphins, and just how big those sharks might be. He hit upon the idea of making a dolphin shape out of gelatin—essentially the same stuff FIU’s forensic department uses for ballistic tests—and asked his forensic colleagues to make one for him, since the material has the same weight and density of dolphin blubber.
For the Edgley documentary, they made a large gelatin lollipop the same density as whale blubber, and he and Edgley dove down and managed to get an 11-foot tiger shark to take a big 6.2-pound bite out of it. We know how many calories are in whale blubber so Heithaus was able to deduce from that how many calories per bite a tiger shark consumed (6.2 pounds of whale meet is equivalent to about 25,000 calories).
Such field work also lets him gather ever mire specimens of shark bites from a range of species for his research. “The great thing about SHARKFEST is that you’re seeing new, cutting-edge science that may or may not work,” said Heithaus. “But that’s what science is about: trying things and advancing our knowledge even if it doesn’t work al the time, and then sharing that information and excitement with the public.”
Then it was time for Edgley to make like a migrating shark and embark on a carefully designed famine-and-feast regime. First, his weight and body volume were measured in a “Bodpod”: 190.8 pounds and 140.8 pints. Then Edgley fasted and exercised almost continuously for 24 hours with a mix of weight training, running, swimming, sitting in the sauna, and climate chamber cycling. (He did sleep for a few hours.) He dropped 14 pounds and lost twelve pints, ending up at a weight of 177 pounds and a volume of 128.7 pints. Instead of food, what he craved most at the end was water. “When you are in a completely deprived state, you find out what your body actually needs, not what it wants,” said Edgley.
After slaking his thirst, it was time to gorge. Over the next 24 hours, Edgley consumed an eye-popping 35,103 calories in carefully controlled servings. It’s quite the menu: Haribo mix, six liters of Lucozade, a Hulk smoothie, pizza, five slices of lemon blueberry cheesecake, five slices of chocolate mint cheesecake, fish and chips, burgers and fries, two cinnamon loaves, four tubs of Ben & Jerry’s ice cream, two full English breakfasts, five liters of custard, four mars bars, and four mass gainer shakes.
When his weight and volume were measured one last time in the Bodpod, Edgley had regained a whopping 22 pounds for a final weight of 199 pounds. “I wish I had Ross’s ability to eat that much and remain at 0 percent body fat,” said Heithaus. Verdict: Edgley is 28 percent tiger shark.
Ross vs. the mako shark
Finally, Edgley pitted himself against the mighty mako shark. Mako sharks are the speediest sharks in the ocean, capable of swimming at speeds up to 43 MPH. Edgley is a long-distance swimmer, not a sprinter, so he threw himself into training at Loughborough University with British Olympians coaching him. He fell far short of a mako shark’s top speed. The shape of the human body is simply much less hydrodynamic than that of a shark. He realized that despite his best efforts, “I was making up hundredths of a second, which is huge in sprinting,” he said. “That could be the difference between a gold medal at the Paris Olympics and not. But I needed to make up many kilometers per hour.”
So Edgley decided to “think like a shark” and employ a shark-like strategy of riding the ocean currents to increase his speed. He ditched the pool and headed to the Menai Strait in Wales for some open water swimming. Ultimately he was able to hit 10.24 MPH—double what an Olympic swimmer could manage in a pool, but just 25 percent of a mako shark’s top speed. And he managed with the help or a team of 20-30 people dropping him into the fastest tide possible. “A mako shark would’ve just gone, ‘This is a Monday morning, this isn’t an event for me, I’m off,'” said Edgley. Verdict: Edgley is 24 percent mako shark
When the results of all four challenges were combined, Edgley came out at 32 percent overall, or nearly one-third shark. While Edgley confessed to being humbled by his limitations, “I don’t think there’s anyone else out there who could do so as well across the board in comparison,” said Heithaus.
The ultimate goal of Shark vs. Ross Edgley—and indeed all of the SHARKFEST programming—is to help shift public perceptions of sharks. “The great Sir David Attenborough said that the problems facing us in terms of conservation is as much a communication issue as a scientific one,” Edgley said. “The only way we can combat that is by educating people.”
Shark populations have declined sharply by 70 percent or more over the last 50 years. “It’s really critical that we protect and restore these populations,” Heithaus said. Tiger sharks, for instance, eat big grazers like turtles and sea cows, and thus protect the sea grass. (Among other benefits, the sea grass sequesters carbon dioxide.) Sharks are also quite sophisticated in their behavior. “Some have social connections with other sharks, although not to the same extent as dolphins,” said Heithaus. “They’re more than just loners, and they may have personalities. We see some sharks that are more bold, and others that are more shy. There’s a lot more to sharks than we would have thought.”
People who hear about Edgley’s basking shark encounter invariably assume he’d been in danger. However, “We were friends. I’m not on its menu,” Edgley said. “There are so many different species.” He likened it to being chased by a dog. People might assume it was a rottweiler giving chase, when in fact the basking shark is the equivalent of a poodle. “Hopefully what people take away from this is moving from a fear and misunderstanding of sharks to respect and admiration,” Edgley said. “That’ll make the RAF fighter pilot plane worth it.”
And he’s game to take on even more shark challenges in the future. There are a lot more shark species out there, after all, just waiting to go head-to-head with a human ultra-athlete.
Shark vs. Ross Edgley premieres on Sunday, June 30, 2024, on Disney+.
A small group of woolly mammoths became trapped on Wrangel Island around 10,000 years ago when rising sea levels separated the island from mainland Siberia. Small, isolated populations of animals lead to inbreeding and genetic defects, and it has long been thought that the Wrangel Island mammoths ultimately succumbed to this problem about 4,000 years ago.
A paper in Cell on Thursday, however, compared 50,000 years of genomes from mainland and isolated Wrangel Island mammoths and found that this was not the case. What the authors of the paper discovered not only challenges our understanding of this isolated group of mammoths and the evolution of small populations, it also has important implications for conservation efforts today.
A severe bottleneck
It’s the culmination of years of genetic sequencing by members of the international team behind this new paper. They studied 21 mammoth genomes—13 of which were newly sequenced by lead author Marianne Dehasque; others had been sequenced years prior by co-authors Patrícia Pečnerová, Foteini Kanellidou, and Héloïse Muller. The genomes were obtained from Siberian woolly mammoths (Mammuthus primigenius), both from the mainland and the island before and after it became isolated. The oldest genome was from a female Siberian mammoth who died about 52,300 years ago. The youngest were from Wrangel Island male mammoths who perished right around the time the last of these mammoths died out (one of them died just 4,333 years ago).
It’s a remarkable and revealing time span: The sample included mammoths from a population that started out large and genetically healthy, went through isolation, and eventually went extinct.
Mammoths, the team noted in their paper, experienced a “climatically turbulent period,” particularly during an episode of rapid warming called the Bølling-Allerød interstadial (approximately 14,700 to 12,900 years ago)—a time that others have suggested might have led to local woolly mammoth extinctions. However, the genomes of mammoths studied through this time period don’t indicate that the warming had any adverse effects.
Adverse effects only appeared—and drastically so—once the population was isolated on that island.
The team’s simulations indicate that, at its smallest, the total population of Wrangel Island mammoths was fewer than 10 individuals. This represents a severe population bottleneck. This was seen genetically through increased runs of homozygosity within the genome, caused when both parents contribute nearly identical chromosomes, both derived from a recent ancestor. The runs of homozygosity within isolated Wrangel Island mammoths were four times as great as those before sea levels rose.
Despite that dangerously tiny number of mammoths, they recovered. The population size, as well as inbreeding level and genetic diversity, remained stable for the next 6,000 years until their extinction. Unlike the initial population bottleneck, genomic signatures over time seem to indicate inbreeding eventually shifted to pairings of more distant relatives, suggesting either a larger mammoth population or a change in behavior.
Within 20 generations, their simulations indicate, the population size would have increased to about 200–300 mammoths. This is consistent with the slower decrease in heterozygosity that they found in the genome.
Long-lasting negative effects
The Wrangel Island mammoths may have survived despite the odds, and harmful genetic defects may not have been the reason for their extinction, but the research suggests their story is complicated.
At about 7,608 square kilometers today, a bit larger than the island of Crete, Wrangel Island would have offered a fair amount of space and resources, although these were large animals. For 6,000 years following their isolation, for example, they suffered from inbreeding depression, which refers to increased mortality as a result of inbreeding and its resulting defects.
That inbreeding also boosted the purging of harmful mutations. That may sound like a good thing—and it can be—but it typically occurs because individuals carrying two copies of harmful mutations die or fail to reproduce. So it’s good only if the population survives it.
The team’s results show that purging genetic mutations can be a lengthy evolutionary process. Lead author Marianne Dehasque is a paleogeneticist who completed her PhD at the Centre for Palaeogenetics. She explained to Ars that, “Purging harmful mutations for over 6,000 years basically indicates long-lasting negative effects caused by these extremely harmful mutations. Since purging in the Wrangel Island population went on for such a long time, it indicates that the population was experiencing negative effects from these mutations up until its extinction.”
While CRISPR is probably the most prominent gene-editing technology, there are a variety of others, some developed before, others since. And people have been developing CRISPR variants to perform more specialized functions, like altering specific bases. In all of these cases, researchers are trying to balance a number of competing factors: convenience; flexibility; specificity and precision for the editing; low error rates; and so on.
So, having additional options for editing can be a good thing, enabling new ways of balancing those different needs. On Wednesday, a pair of papers in Nature describe a DNA-based parasite that moves itself around bacterial genomes through a mechanism that hasn’t been previously described. It’s nowhere near ready for use in humans, but it may have some distinctive features that make it worth further development.
Going mobile
Mobile genetic elements, commonly called transposons, are quite common in many species—they make up nearly half the sequences in the human genome, for example. They are indeed mobile, showing up in new locations throughout the genome, sometimes by cutting themselves out and hopping to new locations, other times by sending a copy out to a new place in the genome. For any of this to work, they need to have an enzyme that cuts DNA and specifically recognizes the right transposon sequence to insert into the cut.
The specificity of that interaction, needed to ensure the system only inserts new copies of itself, and the cutting of DNA, are features we’d like for gene editing, which places a value on better understanding these systems.
Bacterial genomes tend to have very few transposons—the extra DNA isn’t really in keeping with the bacterial reproduction approach of “copy all the DNA as quickly as possible when there’s food around.” Yet bacterial transposons do exist, and a team of scientists based in the US and Japan identified one with a rather unusual feature. As an intermediate step in moving to a new location, the two ends of the transposon (called IS110) are linked together to form a circular piece of DNA.
In its circular form, the DNA sequences at the junction act as a signal that tells the cell to make an RNA copy of nearby DNA (termed a “promoter”). When linear, each of the two bits of DNA on either side of the junction lacks the ability to act as a signal; it only works when the transposon is circular. And the researchers confirmed that there is in fact an RNA produced by the circular form, although the RNA does not encode for any proteins.
So, the research team looked at over 100 different relatives of IS110 and found that they could all produce similar non-protein-coding RNAs, all of which shared some key features. These included stretches where nearby sections of the RNA could base-pair with each other, leaving an unpaired loop of RNA in between. Two of these loops contained sequences that either base-paired with the transposon itself or at the sites in the E. coli genome where it inserted.
That suggests that the RNA produced by the circular form of the transposon helped to act as a guide, ensuring that the transposon’s DNA was specifically used and only inserted into precise locations in the genome.
Editing without precision
To confirm this was right, the researchers developed a system where the transposon would produce a fluorescent protein when it was properly inserted into the genome. They used this to show that mutations in the loop that recognized the transposon would stop it from being inserted into the genome—and that it was possible to direct it to new locations in the genome by changing the recognition sequences in the second loop.
To show this was potentially useful for gene editing, the researchers blocked the production of the transposon’s own RNA and fed it a replacement RNA that worked. So, you could potentially use this system to insert arbitrary DNA sequences into arbitrary locations in a genome. It could also be used with targeting RNAs that caused specific DNA sequences to be deleted. All of this is potentially very useful for gene editing.
Emphasis on “potentially.” The problem is that the targeting sequences in the loops are quite short, with the insertion site targeted by a recognition sequence that’s only four to seven bases long. At the short end of this range, you’d expect that a random string of bases would have an insertion site about once every 250 bases.
That relatively low specificity showed. At the high end, various experiments could see an insertion accuracy ranging from a close-to-being-useful 94 percent down to a positively threatening 50 percent. For deletion experiments, the low end of the range was a catastrophic 32 percent accuracy. So, while this has some features of an interesting gene-editing system, there’s a lot of work to do before it could fulfill that potential. It’s possible that these recognition loops could be made longer to add the sort of specificity that would be needed for editing vertebrate genomes, but we simply don’t know at this point.
The humble hagfish is an ugly, gray, eel-like creature best known for its ability to unleash a cloud of sticky slime onto unsuspecting predators, clogging the gills and suffocating said predators. That’s why it’s affectionately known as a “snot snake.” Hagfish also love to burrow into the deep-sea sediment, but scientists have been unable to observe precisely how they do so because the murky sediment obscures the view. Researchers at Chapman University built a special tank with transparent gelatin to overcome this challenge and get a complete picture of the burrowing behavior, according to a new paper published in the Journal of Experimental Biology.
“For a long time we’ve known that hagfish can burrow into soft sediments, but we had no idea how they do it,” said co-author Douglas Fudge, a marine biologist who heads a lab at Chapman devoted to the study of hagfish. “By figuring out how to get hagfish to voluntarily burrow into transparent gelatin, we were able to get the first ever look at this process.”
As previously reported, scientists have been studying hagfish slime for years because it’s such an unusual material. It’s not like mucus, which dries out and hardens over time. Hagfish slime stays slimy, giving it the consistency of half-solidified gelatin. That’s due to long, thread-like fibers in the slime, in addition to the proteins and sugars that make up mucin, the other major component. Those fibers coil up into “skeins” that resemble balls of yarn. When the hagfish lets loose with a shot of slime, the skeins uncoil and combine with the salt water, blowing up more than 10,000 times its original size.
From a materials standpoint, hagfish slime is fascinating stuff that might one day prove useful for biomedical devices, or weaving light-but-strong fabrics for natural Lycra or bulletproof vests, or lubricating industrial drills that tend to clog in deep soil and sediment. In 2016, a group of Swiss researchers studied the unusual fluid properties of hagfish slime, specifically focusing on how those properties provided two distinct advantages: helping the animal defend itself from predators and tying itself in knots to escape from its own slime.
Hagfish slime is a non-Newtonian fluid and is unusual in that it is both shear-thickening and shear-thinning in nature. Most hagfish predators employ suction feeding, which creates a unidirectional shear-thickening flow, the better to clog the gills and suffocate said predators. But if the hagfish needs to get out of its own slime, its body movements create a shear-thinning flow, collapsing the slimy network of cells that makes up the slime.
Fudge has been studying the hagfish and the properties of its slime for years. For instance, way back in 2012, when he was at the University of Guelph, Fudge’s lab successfully harvested hagfish slime, dissolved it in liquid, and then “spun” it into a strong-yet-stretchy thread, much like spinning silk. It’s possible such threads could replace the petroleum-based fibers currently used in safety helmets or Kevlar vests, among other potential applications. And in 2021, his team found that the slime produced by larger hagfish contains much larger cells than slime produced by smaller hagfish—an unusual example of cell size scaling with body size in nature.
A sedimentary solution
This time around, Fudge’s team has turned their attention to hagfish burrowing. In addition to shedding light on hagfish reproductive behavior, the research could also have broader ecological implications. According to the authors, the burrowing is an important factor in sediment turnover, while the burrow ventilation changes the chemistry of the sediment such that it could contain more oxygen. This in turn would alter which organisms are likely to thrive in that sediment. Understanding the burrowing mechanisms could also aid in the design of soft burrowing robots.
But first Fudge’s team had to figure out how to see through the sediment to observe the burrowing behavior. Other scientists studying different animals have relied on transparent substrates like mineral cryolite or hydrogels made of gelatin, the latter of which has been used successfully to observe the burrowing behavior of polychaete worms. Fudge et al. opted for gelatin as a sediment replacement housed in three custom transparent acrylic chambers. Then they filmed the gelatin-burrowing behavior of 25 randomly selected hagfish.
This enabled Fudge et al. to identify two distinct phases of movement that the hagfish used to create their u-shaped burrows. First there is the “thrash” stage, in which the hagfish swims vigorously while moving its head from side to side. This not only serves to propel the hagfish forward, but also helps chop up the gelatin into pieces. This might be how hagfish overcome the challenge of creating an opening in the sediment (or gelatin substrate) through which to move.
Next comes the “wriggle” phase, which seems to be powered by an “internal concertina” common to snakes. It involves the shortening and forceful elongation of the body, as well as exerting lateral forces on the walls to brace and widen the burrow. “A snake using concertina movements will make steady progress through a narrow channel or burrow by alternating waves of elongation and shortening,” the authors wrote, and the loose skin of the hagfish is well suited to such a strategy. The wriggle phase lasts until the burrowing hagfish pops its head out of the substrate. The hagfish took about seven minutes or more on average to complete their burrows.
Naturally there are a few caveats. The walls of the acrylic containers may have affected the burrowing behavior in the lab, or the final shape of the burrows. The authors recommend repeating the experiments using sediments from the natural habitat, implementing X-ray videography of hagfish implanted with radio markers to capture the movements. Body size and substrate type may also influence burrowing behavior. But on the whole, they believe their observations “are an accurate representation of how hagfish are creating and moving within burrows in the wild.”
A key aspect of humans’ evolutionary success is the fact that we don’t have to learn how to do things from scratch. Our societies have developed various ways—from formal education to YouTube videos—to convey what others have learned. This makes learning how to do things far easier than learning by doing, and it gives us more space to experiment; we can learn to build new things or handle tasks more efficiently, then pass information on how to do so on to others.
Some of our closer relatives, like chimps and bonobos, learn from their fellow species-members. They don’t seem to engage in this iterative process of improvement—they don’t, in technical terms, have a cumulative culture where new technologies are built on past knowledge. So, when did humans develop this ability?
Based on a new analysis of stone toolmaking, two researchers are arguing that the ability is relatively recent, dating to just 600,000 years ago. That’s roughly the same time our ancestors and the Neanderthals went their separate ways.
Accumulating culture
It’s pretty obvious that a lot of our technology builds on past efforts. If you’re reading this on a mobile platform, then you’re benefitting from the fact that smartphones were derived from personal computers and that software required working hardware to happen. But for millions of years, human technology lacked the sort of clear building blocks that would help us identify when an archeological artifact is derived from earlier work. So, how do you go about studying the origin of cumulative culture?
Jonathan Paige and Charles Perreault, the researchers behind the new study, took a pretty straightforward approach. To start with, they focused on stone tools since these are the only things that are well-preserved across our species’ history. In many cases, the styles of tools remained constant for hundreds of thousands of years. This gives us enough examples that we’ve been able to figure out how these tools were manufactured, in many cases learning to make them ourselves.
Their argument in the paper they’ve just published is that the sophistication of these tools provides a measure of when cultural accumulation started. “As new knapping techniques are discovered, the frontiers of the possible design space expand,” they argue. “These more complex technologies are also more difficult to discover, master, and teach.”
The question then becomes one of when humans made the key shift: from simply teaching the next generation to make the same sort of tools to using that knowledge as a foundation to build something new. Paige and Perreault argue that it’s a matter of how complex it is to make the tool: “Generations of improvements, modifications, and lucky errors can generate technologies and know-how well beyond what a single naive individual could invent independently within their lifetime.”
The hydra is a Lovecraftian-looking microorganism with a mouth surrounded by tentacles on one end, an elongated body, and a foot on the other end. It has no brain or centralized nervous system. Despite the lack of either of those things, it can still feel hunger and fullness. How can these creatures know when they are hungry and realize when they have had enough?
While they lack brains, hydra do have a nervous system. Researchers from Kiel University in Germany found they have an endodermal (in the digestive tract) and ectodermal (in the outermost layer of the animal) neuronal population, both of which help them react to food stimuli. Ectodermal neurons control physiological functions such as moving toward food, while endodermal neurons are associated with feeding behavior such as opening the mouth—which also vomits out anything indigestible.
Even such a limited nervous system is capable of some surprisingly complex functions. Hydras might even give us some insights into how appetite evolved and what the early evolutionary stages of a central nervous system were like.
No, thanks, I’m full
Before finding out how the hydra’s nervous system controls hunger, the researchers focused on what causes the strongest feeling of satiety, or fullness, in the animals. They were fed with the brine shrimp Artemia salina, which is among their usual prey, and exposed to the antioxidant glutathione. Previous studies have suggested that glutathione triggers feeding behavior in hydras, causing them to curl their tentacles toward their mouths as if they are swallowing prey.
Hydra fed with as much Artemia as they could eat were given glutathione afterward, while the other group was only given only glutathione and no actual food. Hunger was gauged by how fast and how often they opened their mouths.
It turned out that the first group, which had already glutted themselves on shrimp, showed hardly any response to glutathione eight hours after being fed. Their mouths barely opened—and slowly if so—because they were not hungry enough for even a feeding trigger like glutathione to make them feel they needed seconds.
It was only at 14 hours post-feeding that the hydra that had eaten shrimp opened their mouths wide enough and fast enough to indicate hunger. However, those that were not fed and only exposed to glutathione started showing signs of hunger only four hours after exposure. Mouth opening was not the only behavior provoked by hunger since starved animals also somersaulted through the water and moved toward light, behaviors associated with searching for food. Sated animals would stop somersaulting and cling to the wall of the tank they were in until they were hungry again.
Food on the “brain”
After observing the behavioral changes in the hydra, the research team looked into the neuronal activity behind those behaviors. They focused on two neuronal populations, the ectodermal population known as N3 and the endodermal population known as N4, both known to be involved in hunger and satiety. While these had been known to influence hydra feeding responses, how exactly they were involved was unknown until now.
Hydra have N3 neurons all over their bodies, especially in the foot. Signals from these neurons tell the animal that it has eaten enough and is experiencing satiety. The frequency of these signals decreased as the animals grew hungrier and displayed more behaviors associated with hunger. The frequency of N3 signals did not change in animals that were only exposed to glutathione and not fed, and these hydra behaved just like animals that had gone without food for an extended period of time. It was only when they were given actual food that the N3 signal frequency increased.
“The ectodermal neuronal population N3 is not only responding to satiety by increasing neuronal activity, but is also controlling behaviors that changed due to feeding,” the researchers said in their study, which was recently published in Cell Reports.
Though N4 neurons were only seen to communicate indirectly with the N3 population in the presence of food, they were found to influence eating behavior by regulating how wide the hydras opened their mouths and how long they kept them open. Lower frequency of N4 signals was seen in hydra that were starved or only exposed to glutathione. Higher frequency of N4 signals were associated with the animals keeping their mouths shut.
So, what can the neuronal activity of a tiny, brainless creature possibly tell us about the evolution of our own complex brains?
The researchers think the hydra’s simple nervous system may parallel the much more complex central and enteric (in the gut) nervous systems that we have. While N3 and N4 operate independently, there is still some interaction between them. The team also suggests that the way N4 regulates the hydra’s eating behavior is similar to the way the digestive tracts of mammals are regulated.
“A similar architecture of neuronal circuits controlling appetite/satiety can be also found in mice where enteric neurons, together with the central nervous system, control mouth opening,” they said in the same study.
The development of gene editing tools, which enable the specific targeting and correction of mutations, hold the promise of allowing us to correct those mutations that cause genetic diseases. However, the technology has been around for a while now—two researchers were critical to its development in 2020—and there have been only a few cases where gene editing has been used to target diseases.
One of the reasons for that is the challenge of targeting specific cells in a living organism. Many genetic diseases affect only a specific cell type, such as red blood cells in sickle-cell anemia, or specific tissue. Ideally, to limit potential side effects, we’d like to ensure that enough of the editing takes place in the affected tissue to have an impact, while minimizing editing elsewhere to limit side effects. But our ability to do so has been limited. Plus, a lot of the cells affected by genetic diseases are mature and have stopped dividing. So, we either need to repeat the gene editing treatments indefinitely or find a way to target the stem cell population that produces the mature cells.
On Thursday, a US-based research team said that they’ve done gene editing experiments that targeted a high-profile genetic disease: cystic fibrosis. Their technique largely targets the tissue most affected by the disease (the lung), and occurs in the stem cell populations that produce mature lung cells, ensuring that the effect is stable.
Getting specific
The foundation of the new work is the technology that gets the mRNAs of the COVID-19 mRNA vaccines inside cells. The nucleic acids of an mRNA are large molecules with a lot of charged pieces, which makes it difficult for them to cross a membrane to get inside of a cell. To overcome that problem, the researchers package the mRNA inside a bubble of lipids, which can then fuse with cell membranes, dumping the mRNA inside the cell.
This process, as the researchers note, has two very large advantages: We know it works, and we know it’s safe. “More than a billion doses of lipid nanoparticle–mRNA COVID-19 vaccines have been administered intramuscularly worldwide,” they write, “demonstrating high safety and efficacy sustained through repeatable dosing.” (As an aside, it’s interesting to contrast the research community’s view of the mRNA vaccines to the conspiracies that circulate widely among the public.)
There’s one big factor that doesn’t matter for vaccine delivery but does matter for gene editing: They’re not especially fussy about what cells they target for delivery. So, if you want to target something like blood stem cells, then you need to alter the lipid particles in some way to get them to preferentially target the cells of your choice.
There are a lot of ideas on how to do this, but the team behind this new work found a relatively simple one: changing the amount of positively charged lipids on the particle. In 2020, they published a paper in which they describe the development of selective organ targeting (SORT) lipid nanoparticles. By default, many of the lipid particles end up in the liver. But, as the fraction of positively charged lipids increases, the targeting shifts to the spleen and then to the lung.
So, presumably, because they know they can target the lung, they decided to use SORT particles to send a gene editing system specific to cystic fibrosis, which primarily affects that tissue and is caused by mutations in a single gene. While it’s relatively easy to get things into the lung, it’s tough to get them to lung cells, given all the mucus, cilia, and immune cells that are meant to take care of foreign items in the lung.
Long before humans became interested in killing bacteria, viruses were on the job. Viruses that attack bacteria, termed “phages” (short for bacteriophage), were first identified by their ability to create bare patches on the surface of culture plates that were otherwise covered by a lawn of bacteria. After playing critical roles in the early development of molecular biology, a number of phages have been developed as potential therapies to be used when antibiotic resistance limits the effectiveness of traditional medicines.
But we’re relative latecomers in terms of turning phages into tools. Researchers have described a number of cases where bacteria have maintained pieces of disabled viruses in their genomes and converted them into weapons that can be used to kill other bacteria that might otherwise compete for resources. I only just became aware of that weaponization, thanks to a new study showing that this process has helped maintain diverse bacterial populations for centuries.
Evolving a killer
The new work started when researchers were studying the population of bacteria associated with a plant growing wild in Germany. The population included diverse members of the genus Pseudomonas, which can include plant pathogens. Normally, when bacteria infect a new victim, a single strain expands dramatically as it successfully exploits its host. In this case, though, the Pseudomonas population contained a variety of different strains that appeared to maintain a stable competition.
To learn more, the researchers obtained over 1,500 individual genomes from the bacterial population. Over 99 percent of those genomes contained pieces of virus, with the average bacterial strain having two separate chunks of virus lurking in their genomes. All of these had missing parts compared to a functional virus, suggesting they were the product of a virus that had inserted in the past but had since picked up damage that disabled them.
On its own, that’s not shocking. Lots of genomes (including our own) have plenty of disabled viruses in them. But bacteria tend to eliminate extraneous DNA from their genomes fairly quickly. In this case, one particular viral sequence appeared to date back to the common ancestor of many of the strains since all of them had the virus inserted at the same location of the genome, and all instances of this particular virus had been disabled by losing the same set of genes. The researchers termed this sequence VC2.
Many phages have a stereotypical structure: a large “head” that contains their genetic material, perched on top of a stalk that ends in a set of “legs” that help latch on to their bacterial victims. Once the legs make contact, a stalk contracts, an action that helps transfer the virus’ genome into the bacterial cell. In VC2’s case, all copies of it lacked the genes for producing the head section, as well as all the genes needed for processing its genome during infection.
This made the researchers suspect VC2 was something called a “tailocin.” These are former phages that have been domesticated by bacteria so they can be used to harm the bacteria’s potential competition. Bacteria with a tailocin can produce partial phages that consist only of the legs and stalk. These tailocins can still find and latch on to other bacteria, but when the stalk contracts, there’s no genome to inject. Instead, this just opens a hole in the membrane of their victim, partially eliminating the boundary of the cell and allowing some of its contents to leak out, leading to its death.
An evolutionary free-for-all
To confirm that the VC2 sequence encodes a tailocin, the researchers grew some bacteria that contained the sequence, purified proteins from it, and used electron microscopy to confirm that they contained headless phages. Exposing other bacteria to the tailocin, they found that while the strain that produced it was immune, many other strains growing in the same environment were killed by it. When the team deleted the genes that encode key parts of the tailocin, the killing went away.
The researchers hypothesize that the system is used to kill off potential competition but that many strains have evolved resistance to the tailocin.
When the researchers did a genetic screen to identify resistant mutants, they found that resistance was provided by mutations that interfered with the production of complex sugar molecules that are found on proteins that end up on the exterior of cells. At the same time, most of the genetic differences among the VC2 genes occur in the proteins that encode the legs, which latch on to these sugars.
So it appears that every bacterial strain is both an aggressor and a victim, and there’s an evolutionary arms race that leads to a complex collection of pairwise interactions among the strains—think of a rock/paper/scissors game with dozens of options. And the arms race has a history. Using old samples, the researchers show that many of the variations in these genes have been around for at least 200 years.
Evolutionary competitions are often viewed as a simple one-against-one fight, probably because it’s an easy way to think about them. But the reality is that most are more akin to a chaotic bar room brawl—one where it’s rare for any faction to obtain a permanent advantage.
Outliers among mammals, monotremes lay eggs instead of giving birth to live young. Only two types of monotremes, the platypus and echidna, still exist, but more monotreme species were around about 100 million years ago. Some of them might possibly be even weirder than their descendants.
Monotreme fossils found in refuse from the opal mines of Lightning Ridge, Australia, have now revealed the opalized jawbones of three previously unknown species that lived during the Cenomanian age of the early Cretaceous. Unlike modern monotremes, these species had teeth. They also include a creature that appears to have been a mashup of a platypus and echidna—an “echidnapus.”
Fossil fragments of three known species from the same era were also found, meaning that at least six monotreme species coexisted in what is now Lightning Ridge. According to the researchers who unearthed these new species, the creatures may have once been as common in Australia as marsupials are today.
“[This is] the most diverse monotreme assemblage on record,” they said in a study recently published in Alcheringa: An Australasian Journal of Paleontology.
The Echidnapus emerges
Named Opalios spendens, the “echidnapus” shows similarities to both ornithorhynchoids (the platypus and similar species) and tachyglossids (echidna and similar species). It is thought to have evolved before the common ancestor of either extant monotreme.
The O. splendens holotype had been fossilized in opal like the other Lightning Ridge specimens, but unlike some, it is preserved so well that the internal structure of its bones is visible. Every mammalian fossil from Lightning Ridge has been identified as a monotreme based partly on their peculiarly large dental canals. While the fossil evidence suggests the jaw and snout of O. splendens are narrow and curved, similar to those of an echidna, it simultaneously displays platypus features.
So what relates the echidnapus to a platypus? Despite its jaw being echidna-like at first glance, its dentary, or the part of the jaw that bears the teeth, is similar in size to that of the platypus ancestor Ornithorhynchus anatinus. Other features related more closely to the platypus than the echidna have to do with its ramus, or the part of the jaw that attaches to the skull. It has a short ascending ramus (the rear end) and twisted horizontal ramus (the front end) that are seen in other ornithorhynchoids.
Another platypus-like feature of O. splendens is the flatness of the front of its lower jaw, which is consistent with the flatness of the platypus snout. The size of its jaw also suggests a body size closer to that of a platypus. Though the echidnapus had characteristics of both surviving monotremes, neither of those have the teeth found on this fossil.
My, what teeth you don’t have
Cretaceous monotremes might not have had as many teeth as the echidnapus, but they all had some teeth. The other two new monotreme species that lived among the Lightning Ridge fauna were Dharragarra aurora and Parvopalus clytiei, and the jaw structure of each of these species is either closer to the platypus or the echidna. D. aurora has the slightly twisted jaw and enlarged canal in its mandible that are characteristic of an ornithorhynchoid. It might even be on the branch that gave rise the platypus.
P. clytiei is the second smallest known monotreme (after another extinct species named Teinolophos trusleri). It was more of an echidna type, with a snout that was curved and deep like that of a tachyglossid rather than flat like that of an ornithorhynchoid. It also had teeth, though fewer than the echidnapus. Why did those teeth end up disappearing altogether in modern monotremes?
Monotremes without teeth came onto the scene when the platypus (Ornithorhynchus anatinus) appeared during the Pleistocene, which began 2.6 million years ago. The researchers think competition for food caused the disappearance of teeth in the platypus—the spread of the Australo-New Guinean water rat may have affected which prey platypuses hunted for. Water rats eat mostly fish and shellfish along with some insects, which are also thought to have been part of the diet of ancient ornithorhynchoids. Turning to softer food to avoid competition may explain why the platypus evolved to be toothless.
As for echidnas, tachyglossids are thought to have lost their teeth after they diverged from ornithorhynchoids near the end of the Cretaceous. Echidnas are insectivores, grinding the hard shells of beetles and ants with spines inside their mouths, so have no need for teeth.
Although there is some idea of what happened to their teeth, the fate of the diverse species of Cretaceous monotremes, which were not only toothy but mostly larger than the modern platypus and echidna, remains unknown. The end of the Cretaceous brought a mass extinction triggered by the Chicxulub asteroid. Clearly, some monotremes survived it, but no monotreme fossils from the time have surfaced yet.
“It is unclear whether diverse monotreme fauna survived the end-Cretaceous mass extinction event, and subsequently persisted,” the researchers said in the same study. “Filling this mysterious interval of monotreme diversity and adaptive development should be a primary focus for research in the future.”