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Could Life Use a Longer Genetic Code? Maybe, but It’s Unlikely

Could Life Use a Longer Genetic Code? Maybe, but It’s Unlikely

As wildly diverse as life on Earth is—whether it’s a jaguar hunting down a deer in the Amazon, an orchid vine spiraling around a tree in the Congo, primitive cells growing in boiling hot springs in Canada, or a stockbroker sipping coffee on Wall Street—at the genetic level, it all plays by the same rules. Four chemical letters, or nucleotide bases, spell out 64 three-letter “words” called codons, each of which stands for one of 20 amino acids. When amino acids are strung together in keeping with these encoded instructions, they form the proteins characteristic of each species. With only a few obscure exceptions, all genomes encode information identically.

Yet, in a new study published last month in eLife, a group of researchers at the Massachusetts Institute of Technology and Yale University showed that it’s possible to tweak one of these time-honored rules and create a more expansive, entirely new genetic code built around longer codon words. In principle, their discovery points to one of several ways of expanding the genetic code into a more versatile system that synthetic biologists could use to create cells with novel biochemistries that make proteins found nowhere in nature. But the work also showed that an extended genetic code is hampered by its own complexity, becoming less efficient and even surprisingly less capable in some ways—limitations that hint at why life may not have favored longer codons in the first place.

It’s uncertain what these findings mean for how life elsewhere in the universe could be encoded, but it does imply that our own genetic code evolved to be neither too complicated nor too restrictive, but just right—and then ruled life for billions of years thereafter as what Francis Crick called a “frozen accident.” Nature opted for this Goldilocks code, the authors say, because it was simple and sufficient for its purposes, not because other codes were unachievable.

For example, with four-letter (quadruplet) codons, there are 256 unique possibilities, not just 64, which might seem advantageous for life because it would open opportunities to encode vastly more than 20 amino acids and an astronomically more diverse array of proteins. Previous synthetic biology studies, and even some of those rare exceptions in nature, showed that it’s sometimes possible to augment the genetic code with a few quadruplet codons, but until now, no one has ever tackled creating an entirely quadruplet genetic system to see how it compares with the normal triplet-codon one.

“This was a study that asked that question quite genuinely,” said Erika Alden DeBenedictis, the lead author of the new paper, who was a doctoral student at MIT during the project and is currently a postdoc at the University of Washington.

Expanding on Nature

To test a quadruplet-codon genetic code, DeBenedictis and her colleagues had to modify some of life’s most fundamental biochemistry. When a cell makes proteins, snippets of its genetic information first get transcribed into molecules of messenger RNA (mRNA). The organelles called ribosomes then read the codons in these mRNAs and match them up with the complementary “anti-codons” in transfer RNA (tRNA) molecules, each of which carries a uniquely specified amino acid in its tail. The ribosomes link the amino acids into a growing chain that eventually folds into a functional protein. Once their job is complete and the protein is translated, the mRNAs get degraded for recycling and the spent tRNAs get reloaded with amino acids by synthetase enzymes.

The researchers tweaked the tRNAs in Escherichia coli bacteria to have quadruplet anti-codons. After subjecting the genes of the E. coli to various mutations, they tested whether the cells could successfully translate a quadruplet code, and if such a translation would cause toxic effects or fitness defects. They found that all of the modified tRNAs could bind to quadruplet codons, which showed that “there’s nothing biophysically wrong with doing translation with this larger codon size,” DeBenedictis said.

But they also found that the synthetases only recognized nine out of 20 of the quadruplet anticodons, so they couldn’t recharge the rest with new amino acids. Having nine amino acids that can be translated with a quadruplet codon to some degree is “both a lot and a little,” DeBenedictis said. “It’s a lot of amino acids for something that nature doesn’t ever need to work.” But it’s a little because the inability to translate 11 essential amino acids strictly limits the chemical vocabulary that life has to play with.

How Realistic Is the Celestial Navigation in Moon Knight?

How Realistic Is the Celestial Navigation in Moon Knight?

Our planet also changes positions. In six months, the Earth will go from one side of the sun to the other. This is a change in distance of almost 300 million kilometers, and it’s enough to cause a noticeable apparent position change for some of the nearest stars. In fact, parallax is an important tool for measuring the distance to these stars. (Here are the other ways to measure stellar distances.)

So, yes, constellations change—but not that much.

Finding Your Longitude

Here’s how to find your longitude with a clock and a star chart. Let’s start with the star chart. Suppose there is a star on that chart that will always be directly above a point in Greenwich, England, at 4 am local time, which we would call Greenwich Mean Time. (I didn’t pick Greenwich at random. The prime meridian, or the 0 degree longitude line, runs right through the Royal Observatory Greenwich, so it’s good for measurements.)

Now let’s imagine that you are in another location and trying to figure out where you are by using that same star. You will need to know what time it is when that star appears directly overhead at your location. Hence the clock.

Checking the time reveals that, where you are, that star appears directly overhead at 1 am, instead of 4 am—three hours earlier than Greenwich. That means you are three out of 24 hours to the west of Geenwich. If you want to convert that to degrees, it would be (3/24) × 360 = 45 degrees. That would put you on a longitude line that runs through Greenland and Brazil. (Things can get a bit more complicated than this, since you likely wouldn’t have a star directly overhead, but you get the idea.)

Next, if you are in the northern hemisphere, you can use the North Star to calculate your latitude and determine your exact location on the planet, which is where those latitude and longitude lines cross. Hopefully, it’s not in the middle of the Atlantic Ocean.

What’s Wrong with Moon Knight?

Now it’s time to talk about Moon Knight. (Some spoilers ahead.) In episode 3, Moon Knight, the earthly avatar of Khonshu, has teamed up with Marc’s wife, Layla. They are trying to find the tomb of the Egyptian god Ammit. If Ammit is freed, she will do some bad stuff to the human race, so they really want to get there first. They put together parts of a burial shroud to form an ancient star chart, and want to use this to find the location of the tomb, which is just like celestial navigation.

But there is a problem: This map was made 2,000 years ago, so the arrangement of the constellations is wrong. The stars have since moved to new positions. Since Moon Knight is the avatar of Khonshu, he uses his powers to move the stars in the sky back into the pattern shown when the map was created. Problem solved. Moon Knight and Layla are able to get to Ammit’s tomb.

A Brain Chemical Helps Neurons Know When to Start a Movement

A Brain Chemical Helps Neurons Know When to Start a Movement

By washing through the brain, neuromodulators “allow you to govern the excitability of a large region of the brain more or less in the same way or at the same time,” said Eve Marder, a neuroscientist at Brandeis University widely recognized for her pioneering studies on neuromodulators in the late 1980s. “You’re basically creating either a local brain wash or more extended brain wash that is changing the state of a lot of networks simultaneously.”

The powerful effects of neuromodulators mean that abnormal levels of these chemicals can lead to numerous human diseases and mood disorders. But within their optimal levels, neuromodulators are like secret puppeteers holding the strings of the brain, endlessly shaping circuits and shifting activity patterns into whatever may be most adaptive for the organism, moment by moment.

“The neuromodulatory system [is] the most brilliant hack you can imagine,” said Mac Shine, a neurobiologist at the University of Sydney. “Because what you’re doing is you’re sending a very, very diffuse signal … but the effects are precise.”

Shifting Brain States

In the past few years, a burst of technological advances has paved the way for neuroscientists to go beyond studies of neuromodulators in small circuits to studies looking across the whole brain in real time. They have been made possible by a new generation of sensors that modify the metabotropic neuronal receptors—making them light up when a specific neuromodulator lands on them.

Yulong Li

The researcher Yulong Li of Peking University in Beijing has developed a number of sensors that are advancing studies of neuromodulators and their effects.Photograph: Tianjun Zhao

The lab of Yulong Li at Peking University in Beijing has developed many of these sensors, beginning with the first sensor for the neuromodulator acetylcholine in 2018. The team’s work lies in “harnessing nature’s design” and taking advantage of the fact that these receptors have already evolved to expertly detect these molecules, said Li.

Jessica Cardin, a neuroscientist at Yale University, calls the recent studies using these sensors “the tip of the iceberg, where there’s going to be this enormous wave of people using all of those tools.”

In a paper posted in 2020 on the preprint server, Cardin and her colleagues became the first to use Li’s sensor to measure acetylcholine across the entire cortex in mice. As a neuromodulator, acetylcholine regulates attention and shifts brain states related to arousal. It was widely believed that acetylcholine always increased alertness by making neurons more independent of the activity in their circuits. Cardin’s team found that this holds true in small circuits with only hundreds to thousands of neurons. But in networks with billions of neurons the opposite occurs: Higher levels of acetylcholine lead to more synchronization of activity patterns. Yet the amount of synchronization also depends on the region of the brain and the arousal level, painting the picture that acetylcholine does not have uniform effects everywhere.

Another study published in Current Biology last November similarly upended long-held notions about the neuromodulator norepinephrine. Norepinephrine is part of a monitoring system that alerts us to sudden dangerous situations. But since the 1970s, it’s been thought that norepinephrine is not involved in this system during certain stages of sleep. In the new study, Anita Lüthi at the University of Lausanne in Switzerland and her colleagues used Li’s new norepinephrine sensor and other techniques to show for the first time that norepinephrine doesn’t shut down during all stages of sleep, and indeed plays a role in rousing the animal if need be.

A New Gas-Guzzling Postal Fleet Could Be Halted by Lawsuits

A New Gas-Guzzling Postal Fleet Could Be Halted by Lawsuits

This story originally appeared on Mother Jones and is part of the Climate Desk collaboration.

The saga of the United States Postal Service’s planned gas-guzzling fleet continues.

Sixteen states and two environmental activist groups—Earthjustice and the National Resources Defense Council—are suing the USPS to halt its purchase of a fleet of of gas-guzzling mail trucks. Postmaster general Louis DeJoy has come under fire in recent months for his decision to move forward with a contract for 165,000 new postal trucks—90 percent of which would run on gas and get just 8.6 miles per gallon.

In their suit, the environmental groups point out that DeJoy did not begin an environmental review of the contract until after the Postal Service had already issued a $483 million initial payment to Oshkosh Defense, the manufacturer of the new trucks. The Environmental Protection Agency has contended that the review itself was flawed.

“Electrifying the Postal Service fleet would reduce smog and particulate matter pollution in nearly every neighborhood in America,” the plaintiffs write. “Postal delivery routes are stop-and-go by nature, which means that gas-powered delivery vehicles idle just outside people’s homes for much of the day. This daily pollution impacts nearly every single resident in the country, but the harmful effects of this pollution are felt most significantly by low-income communities of color, which are often forced to breathe compounding sources of pollution.”

Sixteen state attorneys general filed a separate suit arguing that the USPS’s plan would hinder their own environmental goals. “The Postal Service has a historic opportunity to invest in our planet and in our future,” California attorney general Rob Bonta, who is leading the states’ suit, said in a statement. “Instead, it is doubling down on outdated technologies that are bad for our environment and bad for our communities.”

In March, US representative Gerry Connolly, of Virginia, introduced a bill that would require the USPS to commit to a new fleet of 75 percent electric vehicles, but the proposal hasn’t moved out of committee.

“Once this purchase goes through, we’ll be stuck with more than 100,000 new gas-guzzling vehicles on neighborhood streets, serving homes across our state and across the country, for the next 30 years,” Bonta said. “We’re going to court to make sure the Postal Service complies with the law and considers more environmentally friendly alternatives before it makes this decision.”

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Burning Crops to Capture Carbon? Good Luck Finding Water

Burning Crops to Capture Carbon? Good Luck Finding Water

A major consideration is the kind of crop you’d grow to feed a wide-scale BECCS system. That would probably be switchgrass or Miscanthus, another kind of grass, neither of which need as much water or added nutrients as a crop like corn. “They’re quite efficient,” says David Lawrence, a climate scientist at the National Center for Atmospheric Research and coauthor of the new paper. They’re also perennial crops, so you don’t need to plant and till the ground all the time. “But in the context of the study, we found that despite that, we still are seeing increases in water stress and degraded water quality,” Lawrence adds. “And that is because of the scale of the implementation of BECCS: In this scenario it requires a very large-scale increase in the amount of bioenergy.”

For the US to do its fair share in reducing atmospheric carbon to keep global warming to 2 degrees Celsius—in addition to big cuts in greenhouse gas emissions—it would need to add 460,000 square miles of bioenergy crops if using BECCS, while reforestation would require just 150,000 square miles. With this extra space, BECCS could sequester between 11.4 and 31.2 gigatons of CO2 by 2100, similar to the 19.6 to 30.2 gigatons for reforestation. (For reference, humanity as a whole currently emits almost 40 gigatons a year.) That means reforestation would be a more efficient carbon-negative option because it uses less land to get the same effect. That and all those extra crops would divert water from other needs, like hydrating people. Forests, on the other hand, should be able to take care of themselves. 

Increasingly, though, that’s a big should. A forest is a powerful carbon sequestration tool because it comes with a whole bunch of simultaneous benefits: Let one grow and you get a boost in biodiversity, locals can use it to make money from tourism, and a healthy forest cools a region because plants release water vapor. But forests the world over are threatened with rapidly rising temperatures, calling into question their ability to persist over the coming centuries.

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Put another way: If humanity doesn’t massively reduce emissions, temperatures will continue to skyrocket and we’ll lose forests as carbon-sequestration powerhouses. In the American West, in particular, climate change is supercharging wildfires, so if you put a bunch of effort into restoring a forest and it goes up in flames, all that carbon heads straight back into the atmosphere. (Forests are adapted to burn from time to time, but only mildly—the mega-blazes we’ve been seeing in recent years are far from natural.) And if it remains too hot for the forest to grow back in a healthy way, you can’t sequester that carbon again. “Can we find enough locations where the climate supports the growth of a healthy forest?” asks Lawrence. “That is a very difficult question to answer. Does it make sense to put your efforts into reforestation if that forest is likely to burn? It really is going to be very location-dependent.”

Bioenergy crops may also struggle as the world warms. Switchgrass and Miscanthus are good bioenergy species in part because they’re drought-resistant, but heat stress is still a serious concern—just as our bodies struggle with extreme temperatures, so do plants. Scientists would need to tailor a particular species to a specific environment: In a wetter climate like Florida’s, perhaps a crop like sugarcane would be better. “Finding the right plant for bioenergy production, that is suited to the climate and doesn’t draw more and more water, is a better strategy than thinking that Miscanthus and switchgrass are going to be deployed all across the country as a solution,” says hydrologist Praveen Kumar, who studies bioenergy crops at the University of Illinois but wasn’t involved in the new research.