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So much science starts with deciphering a genome, the blueprint for every being on Earth. With such roadmaps in hand, scientists can trace the evolutionary roots of human language, better understand the intelligence of other animals, or even try to bring wooly mammoths back from extinction.

But most of the genomes previously available are riddled with errors and gaps that too often lead to blind alleys. Enter the Vertebrate Genomes Project (), an ambitious initiative designed to assemble near-perfect genomes for every one of the planet's roughly 70,000 vertebrate species. Erich D. Jarvis, head of the Laboratory of Neurogenetics of Language at Rockefeller and chair of the VGP, envisions a future where such databases pave the way for transformative advancements in conservation, evolutionary biology, and basic science.

As if that weren't ambitious enough, this initiative provided the inspiration for—and is now part of—an even greater moonshot: sequencing high-quality genomes for all 1.8 million eukaryotic species on Earth, known as the Earth BioGenome Project (EBP).

On the heels of a successful pilot project that focuses on several hundred species representing vertebrate orders, Jarvis, EBP Chair Harris Lewin, and others are now designing a plan to sequence the genomes of every eukaryotic species in U.S. territory.

We spoke with Jarvis and Giulio Formenti, research assistant professor and one of the co-directors of the Vertebrate Genome Laboratory, about the lessons already learned, the rationale behind a U.S. species-focused consortium, and where the project is going next.

This is an enormous initiative, with many facets and hurdles. Recently, you helped European scientists launch their own pilot program. Can you talk a little about the logistical side of such an ambitious project?

Jarvis: There's an urgent need for high-quality genome assemblies for species around the world. From a purely scientific perspective, it is best to start sequencing species representing parts of a family tree, regardless of where in the world they are from. Grouping vertebrates by nation is arbitrary; non-human species don't have national boundaries. But many regulatory and funding bodies do.

We found that getting permits and navigating other bureaucracy between countries is a challenge. Because of how the European Union is structured, we were able to help them get a pilot project for 100 species up and running—following lessons learned from the VGP—without getting bogged down in all that red tape between countries. They received 20 million Euros.

For the VGP, we've already sequenced more than 500 species; the EBP has surpassed 3,000 (which includes the 500 vertebrate species). What we are proposing for the U.S. is 15,000 species to start.

Formenti: The European pilot started during COVID and really came about because of the European Green Deal. Europe wanted to establish continent-wide policies enhancing sustainability across the board. So, preserving natural resources—including biological and ecosystem resources—was a key priority for them. We proposed generating reference genomes to study organisms across Europe and started a pilot project to showcase the usefulness of error-free reference genomes.

It sounds like conservation is a big motivating factor here?

EJ: One of the first endangered species we sequenced at high quality was the kakapo, a flightless parrot. The last of the species lives on isolated islands off the coast of New Zealand, where they got stuck there after the last Ice Age. Working with Nicholas Dussex and Love Dalen of the Center for Palaeogenetics, we found that the Island population of Kakapos survived greater amounts of inbreeding than a small population normally would have, and our sequencing showed that they had hit on a way to purge deleterious mutations that cause diseases.

We've since sequenced other endangered species and learned that the kakapo is not a one-off. Learning more about the principles at work in small populations that somehow developed methods for purging problematic mutations is crucial. Such information can inform conservation strategies by identifying which species are genetically resilient to inbreeding and which require intervention to prevent harmful mutations.

GF: We're also working with organizations involved in de-extinction efforts. For instance, we provided high-quality genomes for Revive & Restore and for Colossal, groups interested in bringing back the passenger pigeon, wooly mammoths and other species that have gone extinct in the last century, which indirectly supports conservation efforts for endangered species. These genomes and tools would also have implications for preserving what life we still have.

There are a lot of fascinating scientific questions beyond conservation that can't be answered without this kind of data. Can you talk about what else we may learn from these genomes?

EJ: Let's start with my own research interests as head of the Laboratory of Neurogenetics of Language at Rockefeller. We made sure to sequence representatives of all the vocal learner lineages and their closest relatives in the initial stages of the VGP. We're soon going to be able to use these high-quality genomes to get at the genetic changes that gave rise to spoken language.

We will also use the genomes to look at the genes expressed in different neurons in vertebrate lineages. This could finally resolve the long-standing question of whether birds and reptiles have neurons that are homologous with those found in the mammalian neocortex. Many researchers believe only mammals have a neocortex, but it could be that other animals are using similar cell types for the same purpose. Answering that question gives us a new understanding of how animal intelligence evolves.

Finally, we will use higher quality assemblies to update the family tree of vertebrates, and even the family tree of genes—figuring out which genes are related to one another. The implications are vast.

You mentioned launching a US-based version of a national EBP project. What made you decide to focus on a new effort here rather than, say, building on the European pilot?

GF: Species in U.S. territories are going extinct by the day. Getting this project off the ground in the U.S. isn't just about catching up with Europe—it's a national priority that will help preserve this country's natural resources.

EJ: Beyond the enormous benefits for science, our proposal would fund not just a particular study or project, but allow us to build an entire infrastructure around high-quality genome sequencing here in the U.S. That's tremendously exciting and would be transformative for the field. By establishing a centralized infrastructure, we can standardize sequencing methods, ensure error-free assemblies, and dramatically scale up the pace of discovery.

What's the status of the U.S.-based effort?

EJ: In case we receive the needed funding, we are working on transforming our Vertebrate Genome Lab at Rockefeller into a National Reference Genome Center, to serve as a core facility for the entire U.S. consortium. That planned consortium includes Rockefeller University—led by me, Formenti, and Jennifer Balacoo, another VGL co-director—along with collaborators at Arizona State University—led by Krystal Tsosie and Harris Lewin—University of Kansas—led by Nico Franz—U.S. museums, and many experts in genomics and species diversity.

We will be able to form a U.S.-wide network. In order to produce high-quality reference genomes for all eukaryotic species in U.S. territory, we're looking at potentially sequencing up to 600,000 species. For context, the Vertebrate Genome Project sequenced more than 500 species over six years.

We've applied for NSF funding to develop protocols for scaling up and the cost of sequencing. We could potentially sequence up to 1,000 genomes per week. This would allow scientists working on this project to sequence 1.8 million eukaryotic species within 10 years.

Funding aside, what challenges does the U.S. project face?

GF: Collecting hundreds of thousands of samples of high quality from the field, preserving them until they can be sequenced, and then doing all the sequencing is quite challenging, especially because the samples are so diverse. Sequencing a beetle is nothing like sequencing a mammal, because extracting enough DNA from a small organism can be very challenging. Many times, sequencing experiments also fail due to DNA quality, contamination from substances in the organism, or foreign contamination—and then you must start over.

Also, while the U.S. is more homogeneous than Europe in terms of language and regulation, it still requires large-scale collaboration between institutions, museums, and field researchers. Sometimes it feels very difficult, almost impossible. But then I remember the Human Genome Project, which demonstrated that once you establish a standardized, high-throughput pipeline for something, what once seemed insurmountable can become routine.

How are you moving forward while you wait to hear about funding?

EJ: Through grassroots efforts. Anyone who has funding and agrees to our consortium's policies can commission high-quality genomes from us, provided the results will be publicly available for science. For example, if someone requests 100 butterfly genomes but doesn't want high-quality assemblies or inclusion in the Earth BioGenome Project, we won't take the project. Producing near-complete, error-free genomes requires specialized techniques—it's an art. With this and other complementary approaches, we've already achieved 80% of the initial phase of the VGP: 230 species representing most vertebrate orders and some invertebrates.