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What can be done with the menagerie of mammalian genomes?



To learn more about humans, a large international team of scientists has spent years hunting down some of the strangest creatures on Earth. They camped on an arctic ice floe to collect the DNA of a single-tusk. narwhalcaught tiny bumblebee bat in the cave-rich region of Southeast Asia and ventured backstage at a Caribbean zoo to draw blood from a slender-faced solenondonone of the few venomous mammals in the world.

The researchers compared the genomes of these mammals with those of a number of others, including the aardvark, meerkat, starfish and humans. In doing so, they were able to identify stretches of DNA that have hardly changed over eons of mammalian evolution and thus may be vital to human health and function.

The genetic database they have compiled includes the complete genomes of 240 species, covering more than 80 percent of the planet’s mammal families (including humans). This could help scientists answer a lot of questions about other animals, such as when and how they evolved, as well as the biological basis for some of their unusual talents.

“What amazingly cool things can these species do that humans can’t?” said Elinor Karlsson, a geneticist at the Chan School of Medicine at the University of Massachusetts and the Broad Institute and co-director of an organization known as Project Zoonomy. “We always like to think of humans as a special species. But it turns out that we’re actually pretty boring in a lot of ways.”

The Zoonomia dataset has limitations. It contains only one genome for each species (with the exception of the domestic dog, which has been sequenced twice), and thousands of mammals are missing.

But in a new batch of papers published in the journal Science on Thursday, the Zoonomia team showcased the power of such multi-species data. And this is just the beginning.

“Sequencing large numbers of genomes is not a trivial task,” said Michael G. Campana, a computational genomicist at the Smithsonian National Zoo and the Institute of Conservation Biology who was not involved in the project. “What really matters is the actual use of that data.”

Here are some of the things Zoonomia scientists are already doing with it:

To find the basis for the exceptional talents of animals, scientists looked for genetic sequences that evolved unusually quickly into species that possessed a particular trait, such as the ability to hibernate.

IN one analysisThe researchers focused on deep hibernators such as the fat-tailed pygmy lemur and the big-eared bat, which can maintain low body temperatures for days or weeks. The researchers found evidence of “accelerated evolution” in various genes, including one known to help protect cells from temperature-related stress and another that suppresses a cellular pathway associated with aging.

“Many hibernating species also have exceptional lifespans,” says Dr. Karlsson said, making her wonder if changes in this gene contribute to their long life?

The researchers also investigated the mammalian sense of smell. Animals have a large set of different olfactory receptors, each capable of binding to specific odor-causing molecules; Species with a large number of olfactory receptor genes usually do not have a sense of smell.

When the Zoonomia team counted the number of these genes in each species, the African bush elephant ranked first with 4199. They were followed by the nine-banded armadillo and Hoffmann’s two-toed sloth, while the Central American agouti came in fourth.

“It turns out the agouti has one of the best olfactory repertoires of any mammal, for completely unknown reasons,” Dr. Carlsson said. “It’s a reminder of how much variety there is that we don’t know about.” (Dogs, she noted, weren’t “particularly special” in this regard.)

On the other hand, cetaceans – a group that includes dolphins and whales – have a markedly small amount of olfactory receptor genes, which makes sense given their aquatic habitat. “They communicate in other ways,” says Kerstin Lindblad-To, a geneticist at the Broad Institute and Uppsala University and another director of the Zoonomy project.

Species with more olfactory receptor genes also tend to have more olfactory turbinates, bony structures in the nasal cavity that aid in the sense of smell. The results show that “if certain traits are important, they develop differently,” says the doctor. said Lindblad-Toch.

She added: “I think one of the important things about our dataset is that it generates a genome sequence for so many different species that people can start learning about their favorite characteristics.”

In February 1925, in the midst of a diphtheria outbreak, a sled dog relay brought an emergency supply of antitoxin to Nome, Alaska, which was isolated by snow. Balto, one of the dogs that ran the last leg of the relay, became famous; when he died a few years later, his stuffed body was on display at the Cleveland Museum of Natural History.

The Zoonomia research team has now used a small piece of this taxidermated fabric to learn more about the famous sled dog and his canine contemporaries. “We took it as a bit of a problem,” said Kathleen Morrill, author of the paper by Balto, who conducted the research as a graduate student at UMass Chan School of Medicine and is now a senior fellow at Colossal Biosciences. “This man is very famous. We know little about its biology. What can we say about its genome?

Balto, they found what was genetically “healthier” than today’s purebred dogs, with more inherent genetic variation and fewer potentially deleterious mutations. This conclusion is likely due to the fact that sled dogs are commonly bred for exercise and may be a mixture of breeds.

The researchers found that Balto also had a set of genetic variants that wolves did not have and that were rare or absent in modern purebred dogs. Many of the variants were in genes involved in tissue development and could affect many traits important to sled dogs, such as skin thickness and joint formation. The Balto had two copies of these variants, one inherited from each parent, which means they were likely at least somewhat common in other Alaskan sled dogs at the time.

“We’re getting a much clearer picture of what it was like and what its population would have looked like,” said Cathy Moon, a research fellow at the University of California, Santa Cruz and author of the paper. “And this is a picture of really well-adapted working sled dogs.”

Scientists have long debated how and when the modern diverse range of mammals appeared. Did the mammalian family tree only branch out after the extinction of the dinosaurs, about 66 million years ago? Or did the process largely take place before the catastrophe?

A new analysis with Zoonomia genomes suggests the answer is both. Mammals first began to diversify about 102 million years ago, when the Earth’s continents fragmented and sea levels began to rise. “This isolated the ancestors of modern lineages across different land masses,” said William Murphy, an evolutionary geneticist at Texas A&M University and author of the paper.

But another surge in diversification occurred after the extinction of the dinosaurs, the researchers found, when the emergence of new lands and the disappearance of dominant reptiles provided mammals with new habitats, resources and opportunities.

“This is a really landmark article,” said Scott Edwards, an evolutionary biologist at Harvard who was not involved in the study. “This is probably the largest attempt of its kind to put mammals on the timeline.”

The Zoonomia package, more broadly, is “a monumental body of work,” he added. “This will really set the standard for our understanding of mammalian evolution in the future.”

Mammals typically inherit two copies of most genetic sequences, one from each parent. Determining how closely these sequences match can provide insight into the size of animal populations in the past; for example, long stretches of matching DNA can be a sign of inbreeding.

One animal’s genome reflects “how closely related its parents and grandparents were, a long time ago,” said Arin Wilder, a conservationist with the San Diego Zoos Wildlife Alliance.

Dr. Wilder and her colleagues used Zoonomia genomes to estimate population sizes of various species throughout history. Compared to species that were historically abundant, species with small populations had more potentially harmful genetic mutations in the past and were more likely to be classified as endangered. International Union for Conservation of Nature.

The researchers also analyzed the genomes of three species whose extinction risk was considered unknown by the IUCN due to lack of data: the killer whale, the Upper Galilee mole rat, and the Javan deer mouse (which looks exactly as advertised). . The results indicated that killer whales may be most at risk.

According to Beth Shapiro, a paleogenetics scientist at the University of California, Santa Cruz and author of the study, this approach could provide a quick way to prioritize species for a more thorough and resource-intensive risk assessment. “It can be a relatively easy way to sort by conservation,” she said.

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Jupiter’s hot youth may have melted its icy moons



As a newborn planet, Jupiter shone brightly in the sky and eclipsed today’s sun from the perspective of the gas giant’s largest moons. This early glow and upcoming visits by several spacecraft could help solve a 40-year-old mystery about the composition of these moons.

For decades, scientists have been trying to understand the strange differences in density of Jupiter’s four Galilean moons, which, in order from closest to the planet to farthest, are Io, Europa, Ganymede, and Callisto. Although these natural satellites must have formed from the same source material and therefore have a similar composition, density measurements show that Callisto and Ganymede are much icier than Europa, and Io has no ice at all. disclosed At a conference last month, Carver Birson, a planetary scientist at Arizona State University, can shed some light on the subject.

Giant planets are formed by the merger and compression of huge volumes of gas and dust. This process releases a lot of excess energy and gives the newborn giants a literal youthful glow that can last for millions of years. This is more than a theory: astronomers regularly use this glow to image young giant exoplanets that would otherwise be lost in the glow of nearby stars. But the less glaring question of how such a glow could shape accompanying moons has been largely unexplored. In the case of Jupiter, computer simulations by Birson and colleagues suggest that the planet’s early glow illuminated its newborn moons and evaporated most of their water over a period of several million years.

“It gave people the opportunity to think about a completely new process,” says Francis Nimmo, who studies icy moons at the University of California, Santa Cruz and was not involved in the study.

Four satellites, one source

The differential compositions of the four Galilean moons have puzzled researchers for decades, ever since the first high-quality satellite density measurements were made. Locked inside Jupiter’s radiation belt and heated from within by the planet’s powerful tidal forces that knead the Moon’s interior like dough, Io is a completely ice-free world of hyperactive volcanoes. A little more distant Europe is also in the grip of the radiation and tides of Jupiter. But more modest levels of internal heating have given the Moon a subsurface ocean and icy crust, rather than lava-spewing calderas. Ganymede and Callisto are relatively inert, rich in ice, and much farther from Jupiter than Io and Europa.

Although the differences in Jupiter’s gravitational hold clearly explain some of the differences between the moons, planetary scientists were still trying to understand how these objects could have a common origin, yet be so different from each other. Just as planets form from spinning protoplanetary disks of gas and dust around nascent protostars, large moons can form from smaller mini-disks around gathering gas giant worlds. Current thinking calls for Jupiter to gain most of its mass very quickly, during the first 10 million years of the solar system’s life, before the light and stellar winds from the ever-brightening sun swept all the gas from the protoplanetary disk.

This relatively compressed timeline means that Jupiter would have had to greedily, quickly gulp gas to reach its current size, which would have caused it to heat up and glow, reaching a temperature estimated at 1,160 degrees Fahrenheit (627 degrees Celsius). For the Galilean moons, which supposedly formed around the same time as Jupiter itself, the planet would have shone like a star in the sky and overwhelmed the light coming from the more distant sun. By carefully modeling the effects of Jupiter’s increased luminosity on the Galilean moons, Birson and his colleagues found that this beam of light could clearly solve the riddle of today’s diverse satellite composition.

Composite image showing Jupiter’s four largest moons in order of increasing distance from the gas giant. From left to right: Io is closest, then Europa, then Ganymede, and finally Callisto. Credit: Universal History Archive/Universal Images Group via Getty Images

Fragrant fresh baked moons

Torn apart by Jupiter’s gravity, Io today is a hellish landscape of volcanic eruptions and is the most active body in the solar system. But the team found that Jupiter’s youthful glow may have originally given Io Earth’s temperatures and perhaps even the ocean. “I think it’s likely that either during Io’s formation or just after Io’s completion, there is some water on the surface,” Birson says.

That would change quickly, Birson said, as Io received about 30 times more energy from Jupiter than it receives from the Sun today. If Io had as much water as its cousin Ganymede currently holds, all that moisture would be quickly removed, and any remaining ocean would evaporate in the first million years of the moon’s existence.

Europa, further away than Io, would have had slightly cooler surface conditions – although they might still have been hot enough for this moon to lose a significant amount of its water. Farther away, on Ganymede, Jupiter would appear barely brighter than today’s Sun, a level of isolation without significant impact on lunar ice. The distant Callisto, sent to the outskirts of the Jupiter system, would not have been impressed by the radiant youth of Jupiter. (All of this assumes the moons were in their current positions. They probably formed closer before migrating to their current locations, however, this means the results of the study are probably only a lower limit on how much each moon was baked by Jupiter. .)

“The advantage of this hypothesis is that there are several tests that you can apply,” says Nimmo.

SOK-y offer

If Europa had lost most of its ice in its lifetime, rather than formed from less ice than its siblings, the remaining hydrogen and oxygen would have a different isotopic fingerprint than the ice on Ganymede and Callisto. Thus, an isotopic comparison of Europa with one or both of the most distant moons could finally reveal the truth about how these moons diverged from their common origin. “The more comparisons you can make [among the chemistries of the moons]the more you will understand how things will develop at this very early time,” says Birson.

This is quite an attractive proposition, given the recent launch of the European Space Agency’s Jupiter Icy Moons Explorer (JUICE) mission. Between 2031 and 2034, JUICE will make 35 flybys of Europa, Callisto and Ganymede before entering orbit around Ganymede. An extended tour can go a long way in determining whether all Galilean moons were born with the same amount of ice. JUICE has a mass spectrometer, which Nimmo says can make important measurements of hydrogen and water vapor that can come into space from moons, specifically Ganymede.

“The question is whether Ganymede provides enough material for the heights that JUICE can sample,” says Nimmo. He remains confident that this will be the case.

Even if JUICE research fails to crack the case, it won’t be the only moon-exploring spacecraft hovering in the Jupiter system. NASA’s Juno mission is already in orbit around the gas giant, and the space agency’s Europa Clipper mission is set to launch next year to travel to the mission’s moon of the same name. The Clipper data should provide a clear comparison of JUICE’s views of Europa’s ice that will be enough to extrapolate and distinguish from what a European spacecraft sees on Ganymede and possibly Callisto.

“Comparisons between moons will be extremely important,” Birson says. “It’s so exciting that JUICE and Europa Clipper will appear almost at the same time and maybe overlap a bit.”

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In the end, the amateur discovers the “Einstein” tile



In his spare time, David Smith designs tiles. In particular, a retired printer and an amateur mathematician put together as many tiles as they can (no gaps allowed) before the pattern either repeats or fails to continue.

Until recently, every form anyone has ever tested has met one of these two fates, despite the scrutiny of many brilliant minds over the past 50 years. Then, one day last November, Smith discovered the only known exception.

13-sided shape

With an app called PolyForm puzzle solver, Smith built a jagged 13-sided shape. Vaguely resembling a cylinder, it began to fill the screen with copies of it. They connected smoothly and, to his surprise, without repetition.

“The tessellations were something I hadn’t seen before,” he says.

Eager to continue his investigation, he cut out dozens of paper copies and started over. One by one the tiles fell into place. They immersed him deeper into the striking visual pattern—and as he grew, so did his excitement.

He showed this promising creation to Craig Kaplan, a computer scientist at the University of Waterloo. “Almost immediately, it felt like he had stumbled upon something new and profound,” Kaplan says.

Although the mathematical proof took longer, their instinct was sound: as they and two other colleagues announced in March, paper which has not yet been peer-reviewed, Smith stumbled upon the long-awaited form of “Einstein”.

Einstein’s elusive tile

The word “einstein” used here has nothing to do with a German physicist. Instead, he evokes the literal meaning of his last name: “one stone”.

It’s a less yawn-inducing nickname for what is technically known as an “aperiodic mono-tile” – a single tile that can fill an endless plane, over and over again for eternity, in a pattern that never repeats.

On a typical bathroom floor, you will find distinct squares, triangles, or hexagons arranged in some sort of clearly visible pattern. Now imagine replacing those neat rows with a decidedly random jumble of blocks, and voila, aperiodic decor.

In other words, there is no section to cut and paste to complete the rest of the jigsaw puzzle.

Other aperiodic tilings

Before the 13-sided “hat” was revealed to Smith, no one could have guessed whether Einstein even existed.

Mathematicians have been after him since 1966, when Robert Berger designed the first set of tiles that could be laid out aperiodically. It was a landmark innovation, but with a bulky 20,246 different shapes, it wasn’t yet a viable option for home remodelers.

As the search for more elegant combinations continued, in just a few years this number dropped from five to single digits. Soon the monotile was within reach.

In 1973 Oxford mathematician and physicist Roger Penrose set a bar on two tiles by arranging a pair of figures called kites and darts in an aperiodic fashion. But then progress stalled, and the last challenge stood for five whole decades.

Read more: How a mathematician solved a problem that puzzled computer scientists for 30 years

In search of the unknown

After so many years, it may seem surprising that an amateur beat the professionals to the finish line. In fact, Smith wasn’t even looking for Einstein. He attributes his success to “mostly perseverance” and perhaps some luck, “although I feel like I was the chosen one,” he says.

Marjorie Seneschal, a professor emeritus at Smith College who has studied tile since the 1970s, notes that the area’s history is littered with the contributions of untrained artisans. Remarkably, around the time Penrose introduced his kites and darts, an amateur and mail sorter named Robert Ammann independently invented a strikingly similar solution.

“It’s a subject where you can literally get down to business,” says the Seneschal, who profiled Ammann in 2004 For Mathematical intellectual. “If you have a good eye and an inquisitive mind, you can find things that other people trying to work with theory can’t find.”

Reduced fragment of tiles with hats. (Source: David Smith, Joseph Samuel Myers, Craig S. Kaplan, Chaim Goodman-Strauss/CC BY-SA 4.0)

Mathematics of patterns

Smith’s ingenuity sets things in motion. But since we’re dealing with an infinite plane, no amount of end tile manipulation can guarantee that the pattern won’t end up starting over again.

The only way to be sure? Mathematical proof. So Smith and Kaplan brought in two more experts: Chaim Goodman-Strauss, a mathematician at the University of Arkansas, and Joseph Myers, a British software engineer.

In fact, aperiodicity is child’s play. Plain old rectangles can satisfy the requirement of non-repeatability, even if you can easily collect them periodically.

The real trick is to find the shape that only works aperiodically, with the right balance of complexity—enough to break the periodic pattern, but not so much that the whole pattern degenerates.

“It’s the magic that makes aperiodicity interesting,” says Kaplan. “They have to do a very careful dance between order and chaos.”

Read more: Is it really impossible to “square the circle”?

Proof of aperiodicity

To make sure the hat hit the mark, Myers first applied a tried and tested method pioneered by Berger himself.

It starts with a set of “metatiles”, simple polygons that roughly resemble small groups of hats. From there, you can combine meta tiles into super tiles, super tiles into super super tiles, and so on ad infinitum.

Their article demonstrates that this hierarchy is the only way to tile the plane with hats, which is tantamount to proving that form will never slip into periodicity. But then Myers fabricated a new type of proof, and to understand it, we need to break the hat down into its main parts.

However exotic the form may seem, it is well known to geometers as polykit; start with a hexagon, draw three lines connecting opposite sides in the middle and you have six kites.

Combine two or more of them and you get a polykit. Add eight together in a particularly fortunate order and you have a groundbreaking mathematical discovery. As the team writes in their article, “the shape is almost mundane in its simplicity.”

Read more: form of insanity

Setting aperiodicity

The 13 sides of the hat have two lengths, and Myers realized that by adjusting the length of any set, he could create new shapes with the same properties. This means that there is not one Einstein, but an infinite family of them, each of which turns into another in a wide spectrum.

At the two extreme points (where the long and short sides disappear) and at the middle point (where they become equal) there are periodic figures that can be used to establish the aperiodicity of the rest.

This intriguing addition to the mosaic proof repertoire gives mathematicians food for thought, but the Seneschal explains that it is rooted in a more traditional strategy.

“There is a connection with a long-standing theory,” she says. “It puts their work on a continuum of not just mosaics, but thinking about mosaics.”

These hat tiles have a local tri-rotation center. (Source: David Smith, Joseph Samuel Myers, Craig S. Kaplan, Chaim Goodman-Strauss/CC BY-SA 4.0)

The first of many Einsteins

By the mere fact of its existence, the hat solved a riddle. But it also creates new ones. Could there have been more Einsteins, for example, apart from this family? The Seneschal suspects that they must be, and that this triumph may revive the search.

One of the most intriguing questions is the reason for its aperiodicity. The “special sauce” is still unknown, as Kaplan put it: “I can’t point to part of the mold and say, ‘That’s why.’

Nicholas de Bruijn, Dutch mathematician, after all explained Penrose tiles as two-dimensional projections of a five-dimensional mosaic. But as far as the theoretical description of the hat is concerned, Kaplan says “we’re not even close to that yet.”

Whether this abstract curiosity applies in the real world remains to be seen.

Read more: 5 interesting facts about Albert Einstein

hat animation

It certainly has a promising future in interior design, especially considering how tightly it fits into the grid of hexagons. They begin to lay it out on the kitchen floor; anyone with a hexagonal mosaic and enough determination can trace the pattern for themselves.

Many aperiodic tiles are roughly superimposed on an ordered background, “but this one,” Kaplan says, “just sits there really well. It’s almost ridiculously well-behaved.”

Assuming the hat does make it to your local home improvement store, keep in mind that the occasional event is not for the faint of heart.

“If you just go blind,” says Kaplan, “you will probably get stuck.” And if, by some miracle, you find a contractor willing to cheer you up, “there will be big labor costs.”

Read more: How mathematicians cracked the cipher of the zodiac killer

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