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The Ambitious Quest To Genetically Map All Known Vertebrates

2024/12/4
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John Hamilton
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John Hamilton:为了解人类和其他动物的差异以及动物间的差异,需要大量的基因组数据。 Eric Jarvis: "基因组方舟"项目旨在收集并保存地球上所有物种的基因密码,这具有重要的科学和保护意义。该项目将测序约7万个物种的基因组,以解答进化和生物学的基本问题,例如是什么让鸟类成为鸟类,哺乳动物成为哺乳动物等。此外,该项目也具有保护濒危物种的道德意义,因为可以记录其基因信息,甚至有助于拯救其种群。 Eric Jarvis: 他从研究舞蹈转向脑科学,再转向基因组学,始终对复杂行为的遗传学感兴趣。早期研究中,他依赖其他科学家提供的基因数据,但发现数据质量差,导致研究效率低下。早期鸟类基因组研究的经验教训是基因组数据的质量至关重要,这促使他参与并领导脊椎动物基因组项目,致力于生产高质量的基因组数据。高质量的基因组数据对于科学研究至关重要,不能仅仅追求数量。 Eric Jarvis: 选择鸭嘴兽作为早期研究对象是因为它代表了哺乳动物进化树基部的分支,有助于理解哺乳动物的起源。该项目有助于研究发声学习和语言的进化,通过比较不同物种的基因组,可以了解控制大脑解剖结构的基因机制。通过研究不同发声学习能力的物种的基因组,可以深入了解发声学习技能的遗传基础。发声学习能力与认知能力高度相关,许多被认为聪明的动物也具有发声学习能力。对基因组的深入理解可能有助于利用基因工程技术来增强或修复人类的发声沟通回路。 Eric Jarvis: 对人类独特性定义的重新思考,人类与其他物种在某些方面具有共同点。 John Hamilton: 到2024年底,脊椎动物基因组项目已经完成了其前260个物种的大约80%的测序工作,这足以开始解答一些基本问题,但要完全理解人类的独特性还需要更多的基因组数据。

Deep Dive

Key Insights

What is the goal of the Vertebrate Genomes Project?

The goal is to sequence the genomes of about 70,000 animal species to create a 'Genome Ark,' aiming to answer fundamental questions about evolution and biology, and to preserve genetic data of species on the verge of extinction.

Why is sequencing the genomes of endangered species important?

Sequencing these genomes allows scientists to capture genetic data before species go extinct, potentially aiding in conservation efforts to save endangered populations.

What is the significance of the platypus in the Vertebrate Genomes Project?

The platypus represents a unique branch of the mammalian family tree, being an egg-laying mammal. Its genome helps scientists understand the genetic differences between egg-laying and placental mammals, shedding light on the origins of mammals.

How does the Vertebrate Genomes Project relate to vocal learning research?

The project provides genomes of species capable of vocal learning, such as songbirds, dolphins, and bats, which helps researchers understand the genetic basis of vocal learning and its evolution across different species.

What are the ethical implications of genetic engineering in relation to vocal learning circuits?

Genetic engineering could potentially enhance or repair vocal communication circuits in humans, which raises ethical concerns about modifying brain circuits and the implications for human behavior and identity.

What is the current progress of the Vertebrate Genomes Project?

By late 2024, the project had completed about 80% of its first 260 species, providing enough data to start answering questions about what makes different animals unique.

Why is high-quality genome sequencing crucial for the project?

High-quality sequencing ensures accurate data, preventing errors that could delay research and waste resources. It allows for more reliable comparative analysis across species.

What is the 'vocal learning cognitive complex'?

It refers to the association between vocal learning and complex behaviors like problem-solving and rhythmic body movements, which often co-evolve in species perceived as intelligent.

Chapters
The human genome project's completion in 2003 opened doors to understanding human genetic makeup, but to truly differentiate humans from other animals, scientists need many more genomes. The Vertebrate Genomes Project aims to sequence about 70,000 species, including those on the verge of extinction, to understand evolution and biology.
  • Completion of the human genome map in 2003 marked a starting point, not an end.
  • The Vertebrate Genomes Project aims to sequence 70,000 species to compare genomes and understand evolutionary differences.
  • The project also serves as a way to preserve genetic information of endangered species before extinction.

Shownotes Transcript

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So here's a question. What makes a human distinctly human? Back in 2003, there was this idea that scientists might be about to answer that question because they had, more or less, completed a map of the human genome. That meant they could read all the genetic instructions you need to build and maintain a member of our species.

But that was really just the beginning, because a genome is the genetic blueprint for just one species. To understand how humans are different from other animals and how animals are different from one another, scientists will need lots of genomes. Fortunately, they're working on it. So we're trying to take one or two individuals per species and sequence the genetic code, the entire code of that animal that represents that species.

and do that for everybody. And we're putting it into a database that we're calling GenomeArc, with the pun intended, like, you know, an arc to basically save the genetic code of all species on the planet. That's Eric Jarvis, a dancer and neuroscientist from Rockefeller University who says these days he is heavily into genomics. He's also an expert on the brain circuits that allow species, including people and some birds, to learn new vocalizations.

Eric chairs the Vertebrate Genomes Project. It's an international group of scientists who plan to sequence the genomes of about 70,000 species. The first phase is focusing on about 260, including bats, a hummingbird, and even a tortoise. Eric says having those genomes will help answer some basic questions about evolution and biology. What makes a bird a bird? What makes a mammal a mammal? What makes a fish a fish? With all these species sequenced, we will be able to

dig in and find those things that make each lineage different from another. And Eric says there's another reason. There's so many species that are on the verge of extinction that there isn't time to do much. We can capture their genetic data before they go extinct or even capture them to help save the population from going extinct.

And so this is a moral reason for me to work on such a project and to be a chair of it. Today on the show, the effort to collect an arc full of animal genomes and what it could mean for our future. Plus, why a platypus qualified for early boarding. You're listening to Shortwave, the science podcast from NPR.

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Support for NPR and the following message come from Edward Jones. What does it mean to be rich? Maybe it's less about reaching a magic number and more about discovering the magic in life. Edward Jones Financial Advisors are people you can count on for financial strategies that help support a life you love. Because the key to being rich is knowing what counts.

Learn about this comprehensive approach to planning at edwardjones.com slash findyourrich. Edward Jones, member SIPC. So Eric, stepping back here for a second, let's talk about your own quest.

I know that dance led you to brain science because you wanted to understand how the brain controls the body. Then brain science led you to study the circuits that allow some birds to learn really complex vocalizations. So how did you get to genetics and genomics? So I was always interested in genetics in general and the genetics of complex behaviors.

And when I started requiring genetic data from multiple species, I was depending on other scientists who are genome experts to produce that data and collaborate with me and we'll use it to find the underlying genetics of vocal learning or flights or something interesting, right?

We did a bunch of bird genomes back in 2014 that made a lot of splash on revising the family tree of birds. We were able to find convergent genetic differences or genes that change in their regulation in the brains of humans and songbirds for speech and singing. And when we went to go study the function of those genes in vocal learning brain circuits,

My students and postdocs were finding all these errors that we had to fix and resequence those genes over again across multiple species, spending not just months, sometimes years and many thousands of dollars to do some of that work over again because of the poor quality genomes. And when I was asked to lead the Vertebrate Genomes Project because of our success with the bird work,

I kind of reluctantly accepted with the agreement with my colleagues in this global project that we're going to make it a mission to produce the highest quality genomic data possible before we embark on sequencing all these species. They agreed, and that's how I got involved in genomics.

And so was that the lesson of the avian phylogenomics project, was get it right? Yeah, we learned the lessons then, you know, in those first few years, that it can't just be about quantity. Otherwise, the science is going to suffer. And so that delayed us by a number of years. So I said, if we're going to put all this effort

into trying to figure out how to produce high quality genomes of humans, of primates, of turtles, of birds, of fish, and they each have different kinds of requirements. Let's just do them all.

How did you decide with the Vertebrate Project, how did you decide which animals to do first? Why did you choose a platypus? Yeah, so platypus, they represent, they're not the placental mammals. They actually lay eggs, right? So they're at the branches at the base of the mammalian family tree, and there are only a few species left in that lineage.

And so having a platypus would help us understand the origin of mammals, right? Would help us understand the genetic differences between egg-laying mammals and in utero mammals, placental mammals. And so I'm curious, I mean, I think of you as somebody who studies vocal learning, you study birds. So what is this project going to do for you in your own research?

Yeah, so my own research on vocal learning and language. So the ability to imitate sounds, like what we're doing now, producing imitated sounds that we've learned throughout adulthood and childhood, that's pretty rare. And we have it, songbirds, parrots, hummingbirds, amongst birds have it.

dolphins, seals, and bats, and amongst mammals, cetaceans. Those are whales and dolphins, actually, and elephants. So it's a pretty rare trait. But all of us that have this ability converged on a similar solution in the brain anatomy that we so far have been able to examine. And we've been looking to find if there's a similar genetic solution that's controlling that brain anatomy that allows us to produce spoken language.

And so in order to answer that question, in order to understand how it evolved, in order to understand is it working similarly or differently in all these different species, we need the genomes of all those different species. And that's how it impacts me personally. Are you going to figure out what brain circuits are needed to produce vocal learning?

Yes, that's my goal. Right. I believe we will get a much better handle on figuring out the underlying genes and what we call the gene network of how those genes interact with each other from having these 260 species.

At the next level, which represents all families, that's going to be over 1,200 species. We've done a study to show that just on behavior alone, that some species of songbirds are more advanced than other species at their ability to imitate sounds, including human speech sounds. Like if Blue Jay is really great, a zebra finch is, you know, okay.

And we found that there's a nice linear correlation between more advanced vocal learning abilities and problem-solving skills. So in phase two, we hope to be able to interrogate the genomes of species that are more advanced or less advanced at particular behaviors and get at the underlying genetics of even more detailed vocal learning skills.

I take it it's not an accident that the species you mentioned that can do vocal learning are species we think of as having pretty advanced brain capacities. Absolutely. So many people don't even realize this. If you ask people to say, what are the smartest animals out there, right, without realizing they'll name a dolphin, they'll say an elephant, right?

They'll say a crow, which is a songbird or a parrot. So there's a high overlap in our natural perceptions of intelligent animals and vocal learners. And so I call this the vocal learning cognitive complex, where the ability to imitate sounds and communicate with learned vocalizations

is associated with a set of complex behaviors that seem to co-evolve together, one of them being problem solving and another being unsuspecting dancing, synchronizing body movements to sound in a very rhythmic way.

that other species can't seem to do as well as vocal learners. You know, when you talk about the similarities in function, it sounds like we may find that we humans have more in common with some birds than we do with, you know, marmosets. That's right. I think it also means for all these species that we're getting the genetic data for, we're going to have to create a trait database for as well.

We can say what the commonalities are and how those commonalities evolved either convergently or inherited from a common ancestor. If we really understand the details of the genetics behind speech production or any of these things, does that suggest that there are going to be ways to use, say, genetic engineering to make those circuits or transfer those circuits?

Yes, actually. That idea is what we're pursuing in my group here to try to genetically engineer or enhance vocal communication circuits, actually in mice. And we just submitted a preprint on this and we'll see how it gets reviewed. But it's one of my favorite experiments because it takes discoveries that we learned through comparative genetics

comparative neuroscience for a complex trait and try to recapitulate the evolution of that ability, I think it'll take us a lot of years to really understand how these brain circuits work even more. But the little steps, you can take a little step and try to engineer these brain circuits. Now, if you're able to do that, let's say in a mouse or repair a brain circuit in the sunburn,

Why not be able to enhance vocal communication circuits in humans or repair them, you know, if there's a disruption in certain connectivity due to stroke or a certain genetic disorder? So that's where genetic engineering would come in. You would rebuild circuits. That's right. Or perhaps put in new circuits that weren't there before. That's right. That's right. I know there are ethical concerns surrounding that, but the day will come.

You think we're ever going to arrive at the answer of what makes us human? Yeah, I think we're going to, my prediction, and it's not even a prediction because we're already finding it out. We're finding out that we have to be careful about making assumptions about what makes us humans or, you know, using the word unique too liberally.

When we talk about ourselves, yes, we can look out there in the rest of the world and find that, you know, we've been the only species that have built these giant tall buildings and airplanes and so forth. But there are other species that are out there building households of natural made products. Bowerbirds, right? That they build houses that last 30 years that they use for made attraction, for, you know, shelter and so forth.

And so we have to also kind of reclassify as to what we think is advanced, complex, intelligent behavior. And I think we're going to learn a lot more than what makes us unique. We're going to learn a lot more about what makes us the same. Eric, thank you so much for taking the time. It's been an absolute pleasure talking to you. Thank you for all the wonderful questions.

By late 2024, the Vertebrate Genomes Project had completed about 80% of its first 260 species. Eric says that's enough data to start answering questions about what makes a bird a bird and what makes a fish a fish. He says it will take many more genomes to understand what makes a human uniquely human.

This episode was produced by Jessica Young. It was edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Kweisi Lee was the audio engineer. Beth Donovan is our senior director. And Colin Campbell is our senior vice president of podcasting strategy. I'm John Hamilton. Thanks for listening to Shortwave from NPR.

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