Podcast: Recoding genomes, and material from the Moon's far side

Host: Nick Howe

Welcome back to the Nature Podcast. This week, we’ll be finding out how researchers are trying to recode the E. coli genome…

Host: Shamini Bundell

And hearing about the materials on the far side of the Moon. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe.

[Jingle]

Host: Nick Howe

Shamini, what do you and I have in common?

Host: Shamini Bundell

Oh, well, we’ve got loads in common, Nick. You know, so, I’m pretty smart and intelligent and you’re… no, never mind. I’m really attractive and… oh, no. Okay, I’m struggling slightly, sorry.

Host: Nick Howe

Okay, well, maybe I should have been a bit clearer. What do you and I and every living organism on the planet have in common?

Host: Shamini Bundell

Well, that just makes it harder. I don’t think there is anything.

Host: Nick Howe

Okay, there is one thing. How about I just tell you?

Host: Shamini Bundell

I feel like maybe that was your plan all along.

Interviewer: Nick Howe

What I was thinking of is the fact that – putting viruses to one side – all organisms use the same code for life to make proteins. You start with DNA and this gets transcribed to RNA and then this gets translated into proteins. To translate RNA to proteins, all organisms use 64 codons, each codon being a set of 3 nucleic acids which tells the translation machinery which amino acid to add to the emerging protein chain.

Interviewee: Jason Chin

Now, there are 20 natural amino acids that biology pretty much universally use these to make proteins, and those 20 natural amino acids are encoded by 64 of these triplet codons, and so that means that many amino acids are encoded by more than one codon. So, if you like there’s a redundancy.

Interviewer: Nick How

This is Jason Chin, a synthetic biologist from the MRC Laboratory of Molecular Biology. This redundancy he’s talking about has made many scientists wonder if it’s possible to reduce the number of codons a cell needs. Already, it’s been shown that a bacterium, E. coli, can function with just 63 codons. But why is this a goal for scientists? Nature has happily been using 64 codons for billions of years and there are advantages to this system. So, why are scientists interested in making cells with fewer codons?

Interviewee: Jason Chin

Instead of having a cell that uses all 64 codons to encode protein synthesis, if some of those codons were removed from the genome, the genetic instruction set, could you then actually reuse some of those codons for encoding new man-made building blocks that we could use to make synthetic polymers in cells.

Interviewer: Nick Howe

So, by reducing the number of codons that a cell needs to function, scientists can borrow those codons to do other things, like making artificial molecules. This is what Jason and his team are trying to achieve, and this week in Nature, they present a paper showing that they’ve reduced the number of codons from 64 to 61 in the entire E. coli genome, without disrupting the cell’s function. They did this by looking for codons that could be replaced with synonym codons that mean the same thing but with a different triplet of nucleic acids. But it’s not as easy as just swapping out all the synonyms. Many of the swaps would leave the cell unable to function, so the team’s first task was to figure out which codons the cell could do without. Each codon occurs thousands of times in an E. coli genome, so Jason’s team had to find a more manageable approach.

Interviewee: Jason Chin

So, in a previous set of experiments, we’d asked the question on a region of the cells genome that encodes a lot of genes that are essential for the cell to survive, whether we could replace particular codons with their synonyms, with codons that encode the same amino acid.

Interviewer: Nick Howe

By changing the codons on a short stretch of essential DNA, Jason could test which codons were indispensable – if the change didn’t work, the bacterium wouldn’t survive. Once he found out which codons cells can do without, he could then attempt to remove them from the whole genome. This required a total of 18,214 genetic changes. Previously, this has been done by getting a whole new genome synthesised with the chosen codons missing, but rebuilding the genome from scratch means it’s far less likely to work when you put it back into the cell. Instead, Jason and his team synthesised short sections of the modified genome, then checked that they were functional by replacing the corresponding short section of the genome in E. coli. Once they were happy with them, they stitched them together into larger chunks, until eventually they had the whole genome. Tom Ellis, a synthetic biologist who wasn’t associated with this study, thinks that this method is a game-changer.

Interviewee: Tom Ellis

I think that workflow is going to become the norm now for everyone who’s doing synthetic genomics experiments.

Interviewer: Nick Howe

Now that the number of codons has been pushed down to 61, what are the next steps? Could we see just 20 codons for 20 amino acids?

Interviewee: Tom Ellis

I seriously doubt that. I think there’s a team in Harvard who are pushing for a 57-codon genome and we might see that someday in the future. For now, 61 is the state of the art. I think there’s already theoretical studies saying that even down at 57, you’re starting to push the limits of what is achievable.

Interviewer: Nick Howe

So, we may not get down to 20 codons, but there are likely more codon reductions on the horizon. 61 is the current number to beat and the methods this study outlines could contribute to further reductions in the future. By standardising these methods, much of the process could even be automated, so many more researchers may be able to work on these problems. Jason Chin thinks the methodology is one of the most important aspects of his team’s work.

Interviewee: Jason Chin

I think one of the remarkable things about the study is that it shows that actually you can find very well-defined rules where actually you systematically replace the codon of interest with the same codon everywhere. As long as you’ve previously identified what a good substitution is, it turns out that you can apply that substitution across the whole genome.

Interviewer: Nick Howe

That was Jason Chin from the MRC Laboratory of Molecular Biology, here in the UK. You also heard from Tom Ellis from Imperial College London. You can find Jason’s paper over at nature.com.

Host: Shamini Bundell

Later in the show, we’ll be hearing how drones might help researchers understand why a storm turns into a tornado – that’s coming up in the News Chat. Now though, it’s time for the Research Highlights, read this week by Anna Nagle.

[Jingle]

Anna Nagle

Humans don’t have a great track record when it comes to pumping pollutants into the atmosphere, but this isn’t a modern phenomenon. The Romans were known to have mined lead for use in things like water pipes and coins, and it appears their mining activities caused a lot more air pollution than previously thought. To get an idea of the impact of these ancient excavations, an international team of researchers investigated 5,000-year-old ice cores taken from the Mont Blanc glacier in the French Alps. Within these cores, the team found evidence of two spikes in atmospheric lead pollution. One coincided with when the Romans were expanding their territory in the second century B. C., and the other when the Roman empire was flourishing, around the year A. D. 120. Levels of lead were at least ten times the background rate, suggesting that mining and smelting the metal caused air pollution for much of Europe. Mine that paper over at Geophysical Research Letters.

[Jingle]

Anna Nagle

The giant panda once thrived across a huge part of Asia, from northern China, to as far south as Vietnam. In the wild today, this iconic bear is only found in a handful of mountain ranges in central China. So, what did this drastic shrinking of territory do to the pandas’ genetic diversity? To find out, a team of researchers sequenced the DNA from a 5,000-year-old panda bone, found in an area far south of where the animals now live. Analysis revealed that the bone belonged to a member of a group of giant pandas that have now vanished. However, this extinct lineage appears to have interbred with ancestors of the modern giant panda several thousand years ago. The researchers behind the work say that although there is genetic diversity among modern panda populations, there was much more diversity in the species before their territory shrank. Read that paper over at Current Biology.

[Jingle]

Host: Shamini Bundell

Next up, reporter Lizzie Gibney has been looking at the first results from China’s mission to the far side of the Moon.

Interviewer: Lizzie Gibney

More than 20 probes have landed on the Moon, but only one has ever landed on its mysterious far side – the hemisphere, that due to a tidal lock with Earth, always faces away from us. That probe was China’s Chang’E-4, which made a historic landing there in January. Probes don’t tend to go to the far side because communicating directly with a lander there is impossible. Chang’E-4 gets around that by talking to Earth via a relay spacecraft, based well beyond the Moon. Chang’E-4 landed in a 2,500-kilometre-wide dip called the South Pole-Aitken basin. It’s a site that’s particularly interesting for scientists. Here’s Bill Bottke, a planetary scientist from the Southwest Research Institute.

Interviewee: Bill Bottke

It’s probably the oldest terrain we have on the Moon. We see the greatest density of craters and basins on the far side, and that tells us the oldest terrains on the Moon are located there. The biggest impact crater on the Moon, that everyone agrees is am impact crater, is this one called South Pole-Aitken basin. It’s over 2,000 kilometres across and we think it’s the oldest impact structure on the Moon.

Interviewer: Lizzie Gibney

Chang’E-4 landed earlier this year in the Von Kármán crater – a smaller dip within the South Pole-Aitken basin – and its rover, Yutu-2, set out to study the terrain around it. Using a spectrometer, it looked at the light reflected off the Moon’s surface. Different materials absorb light in characteristically different ways, revealing their composition. The near side of the moon is mostly covered with mare basalt – a type of rock made of solidified lava. But Yutu-2 may have seen something different on the far side. Here’s Dawei Liu, of the National Astronomical Observatories of the Chinese Academy of Sciences.

Interviewee: Dawei Liu

Because Yutu-2 landed on the floor of the Von Kármán crater, much of the floor should be covered by lava flows, whose dominate mineral should be high-calcium pyroxene and maybe similar to the lunar near-side mare basalts. However, what we found are quite different from near-side mare basalts. We found that they are mainly composed of olivine and a low-calcium pyroxene. So, this is kind of surprising to us.

Interviewer: Lizzie Gibney

The findings are unlike anything ever detected before in the near-side samples, but they do match with evidence seen by orbiters from above. And the team have a theory about what they might be seeing. They think the material might be from the interior of the Moon –matter from within the lunar mantle that could have been churned up when a huge asteroid hit, creating the South Pol-Aitken basin, and then later scattered across the surface by another impact, which created the nearby Finsen impact crater. Here’s Bill again.

Interviewee: Bill Bottke

It could very well be that the Chinese mission has managed to sample or at least understand some of the material that may have come from the very deep interior of the Moon. Now, I will say, with that said, there’s some other possibilities. This may not necessarily be lunar mantle and they discuss that in the paper, but I think it’s an exciting possibility and I think everyone’s going to be very interested to see where this goes when this paper hits the street in a few days.

Interviewer: Lizzie Gibney

If true that this dense material comes from inside the Moon, this backs up something called the lunar magma ocean theory, which says that soon after its formation, the Moon’s surface was hot and molten and then later separated into layers as it solidified. That would have left lighter materials in the surface crust, burying deeper ones within its mantle. Here’s Dawei again.

Interviewee: Dawei Liu

According to this theory, the lighter materials should float to form the lunar crust while the denser minerals, such as olivine, should sink to form the lunar mantle. However, this theory was debated because no direct evidence has been found to indicate that the mantle was dominated by olivine. Thus, whether this theory is correct requires further validating and also it also requires further evidence. Our result attempts to prove that olivine-rich lunar mantle could be right, and thus we’re supporting the lunar magma ocean hypothesis.

Interviewer: Lizzie Gibney

Teasing apart the fingerprints of different materials is complicated, and Dawei is keen to stress that the rover needs to collect a lot more data before his team can confirm that this really is material from inside the mantle. Over the next few months the little rover will analyse the spectra of many more samples, as well as map the geology of the landing site.

Bill says that there’s a lot more we can learn from the Moon.

Interviewee: Bill Bottke

The Moon, in a sense, is like a little accessible planet which is smaller than the Earth, but it did go through this extensive melting, so by studying the Moon and the Moon’s mantle, we can hopefully get at some of the same processes that will tell us how the planets in our solar system came to be the way they are.

Interviewer: Lizzie Gibney

Chang’E-4 still has a lot to do. But it’s not China’s only Moon mission. It will soon be followed by Chang’E-5 in December this year, which will aim to bring back samples from the Moon to Earth.

Interviewee: Dawei Liu

I think in future China has planned many missions – maybe Chang’E-6 or subsequent Chang’E missions. These missions will help us to build a lunar base in future. And also, we try to go to Mars and now the Mars exploration programme is in progress, and our asteroid exploration is also in planning.

Interviewer: Lizzie Gibney

That’s a long shopping list of exciting future missions. The Moon is just the first stepping stone to all of these, says Dawei.

Interviewee: Dawei Liu

The Moon will be one of the most important targets for China’s future deep space exploration.

Host: Shamini Bundell

That was Dawei Liu, and you also heard from Bill Bottke. You can read Dawei’s paper and a News and Views article over at nature.com.

Interviewer: Nick Howe

Finally on this week’s show, it’s time for the News Chat and I’m joined by Richard Van Noorden, features editor here at Nature. Hi, Richard.

Interviewee: Richard Van Noorden

Hi, Nick.

Interviewer: Nick Howe

Thanks for joining me. So, first up today, we’ve got a story on open access. What’s going on here?

Interviewee: Richard Van Noorden

So, our listeners might know that European funders have been leading a charge to get more research published open access, so it might be surprising to learn that the countries that are top of the open-access charts is not actually in Europe, according to a study that’s been shared with us. It turns out the country on top here is Indonesia, maybe the world’s most open-access publishing nation. So, interesting to consider why and also perhaps an artefact of how the study was done, but I think it will open some people’s eyes to the way that open access is being pursued in different countries around the world.

Interviewer: Nick Howe

Well, let’s tackle that interesting question of why then – why might Indonesia be the top country for open access?

Interviewee: Richard Van Noorden

Well, the feeling is that Indonesia does very well because it has a huge surge of local, Indonesian-based open-access journals and this study was done on a database called Crossref, which is an organisation that has thousands of publishers in its community and they share data on millions and millions of articles with Crossref, and Indonesia has registered all of its local journals with Crossref. Also, high in the charts are Brazil, Colombia, Bangladesh, Sri Lanka. All of these countries have portals and journals that support very often low-cost, subsidised, open-access publishing. So, 81% of journal articles with an Indonesian author are available to read for free. The world average, according to this study, is 41%, and countries like the United Kingdom are at about 60% free to read. This is all from the year 2017. So, interesting that these nations that you might not consider seem to be ahead of the game.

Interviewer: Nick Howe

So, with all these local journals that are publishing open access, are these journals just being used in those countries or are they being cited elsewhere?

Interviewee: Richard Van Noorden

So, in principle, anyone can publish on these platforms. In practice, it does tend to be authors from the countries that use it a lot and have heard of it a lot, so it’s very focused on the global south.

Interviewer: Nick HoweSo, could we expect to see this level of open access in countries where there are more established publishing systems?

Interviewee: Richard Van Noorden

The difficulty is that the journals that scientists want to publish in and have the reputation don’t operate on this very low-cost basis. So, any new portals or websites that make for easy publishing have to contend in a kind of reputation war with the very well-known journals. So, it’s not just a case of inventing this from scratch – you have to replace the prestige of what’s already there, and in some of these countries in the global south, they don’t have any prestige to replace so they can build up this alternative publishing programme from scratch.

Interviewer: Nick Howe

And is there anything we can learn from these countries that are doing a lot of open access?

Interviewee: Richard Van Noorden

Well, this is sort of a large discussion about how should we make our articles open and whether science publishing should go along the same commercial lines that it’s been run for the last half-century or so. Does publishing articles have to be as expensive as it currently is, could it be much cheaper, could we learn from the way that governments in Brazil and Indonesia have subsidised low-cost portals that get articles out there? Now, one word of caution – it’s probably true that these articles are not as highly cited, perhaps not as carefully edited or as peer-reviewed as the articles that places like the UK and the United States are publishing in these big, very influential journals, so that’s just a word of caution here. But I think it’s really interesting to see how different countries around the world have approached this open access push.

Interviewer: Nick Howe

So, from open access, for our second story now, we’re moving onto tornadoes and drones, which sounds like a bit of a weird story, Richard. What’s going on here?

Interviewee: Richard Van Noorden

Well, a fleet of drones are going to fly into thunderstorms in the United States to try and figure out which thunderstorms are going to turn into tornadoes. It’s a pretty incredible scientific project.

Interviewer: Nick Howe

Yeah, it sounds pretty incredible. Where do the drones come into this?

Interviewee: Richard Van Noorden

We know the basics of why a thunderstorm forms a tornado, so essentially if you have differences in temperatures between layers of the atmosphere and huge changes in wind speed that whip around a rotating column of air, that’s the recipe for a devastating tornado. The problem is it’s actually really hard to predict which thunderstorms are going to develop into that and which won’t. And the wind speeds inside these things are way too high to fly in a plane, so the idea is to use drones to fly them in to these thunderstorms and look for other small-scale structures that scientists think are crucial to know whether thunderstorms are going to turn into tornadoes.

Interviewer: Nick Howe

So, is this just any old thunderstorm or is there a particular type of thunderstorm that lends itself to becoming a tornado?

Interviewee: Richard Van Noorden

Right, so you definitely need this rotating upward movement of air – that’s what is going to form your tornado, except puzzlingly some don’t. So, about a dozen teams are going to collect information from these things that are called supercells – that’s when you have this rotating air – in a region stretching from North Dakota to Texas and from Iowa to Wyoming. Researchers are going to use drones, weather balloons and radar systems to basically attack the storms from every angle. There’s a sort of hypothetical idea that a stream of cool air near the ground might help to dry tornado formation by speeding up the rate at which warm air is sucked into a supercell, and now they’re going to try and measure it.

Interviewer: Nick Howe

So, what are the researchers hoping to do once they’ve found how these tornadoes form?

Interviewee: Richard Van Noorden

Well, the idea is to essentially discover which supercells are going to form tornadoes and so improve the very high false-positive rate of tornado warning systems. The problem is that tornado warning systems keep predicting tornadoes that don’t actually happen, and if you get overwarned, it’s kind of human reaction to heed those warning less in the future – like crying wolf for tornadoes. So, if they can figure out the signatures of a tornado then the national weather service in the States might one day integrate more drones into their data-gathering and tornado-forecasting process.

Interviewer: Nick Howe

Well, we’ll have to keep an eye on that and see if drones become a common part of tornado forecasts. Richard, thanks for joining me on my first ever News Chat. Listeners, head over to nature.com/news for more on those stories.

Host: Shamini Bundell

That’s it for this week’s show. If you’d like to get in touch with us, you can tweet at us – we’re @NaturePodcast – or you could send us an email – podcast@nature.com. And if you’ve enjoyed the show, tell someone who you think might like it too. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe. See you next time.