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An Interview with Leslie Vosshall: Buzzing About the New Mosquito Reference Genome

Wednesday, November 14, 2018

Photo courtesy of Ben Matthews

The new reference genome for Aedes aegypti, just published in Nature, famously got its start through a crowdsourced effort on social media, beginning with a tweet from Rockefeller University scientist Leslie Vosshall pleading for a better mosquito resource. The insect expert has been studying mosquitoes since 2008 but for most of that time did not have access to a high-quality, highly contiguous assembly.

We chatted with her to learn more about mosquitoes, what’s possible with the new reference genome, and how this new assembly has changed the landscape for understanding mosquito biology and its implications in viral transmission.

 

What made the mosquito genome so challenging to sequence?

It was sequenced 10 years ago but the technology then made it impossible to piece together. It’s extremely repetitive. I like to think it of as a series of blah, blah, blah — many copies of blah, blah, blah and you cannot figure out where it fits in the overall sequence of the genome. What was available in the decade-old genome was thousands and thousands of little pieces. That made it impossible to make any progress in studying the mosquito.

How does SMRT Sequencing fit into the story?

The only way we were able to piece this together is because PacBio [sequencing] allowed us to get really long reads that would bridge all the blah, blah, blah and be able to link the whole thing together.

Now that you have this genome, what’s possible?

Now we know how many genes there are in this deadly insect, and we know where they are on chromosomes. That enables everything that comes after. Until you know where the genes are and how many there are, you can’t figure out where insecticide resistance lies. Now with this new genome we can go in with great precision and find the genes. Then you can try to understand how those animals are becoming resistant and develop insecticides that overcome that resistance.

Another example is that viruses like dengue can replicate in some mosquito strains but not others. There are some strains that are resistant to dengue, and that’s a really cool thing to try to figure out. Again, people had a vague idea that there were resistance genes somewhere and now we can really understand what makes some mosquitoes susceptible to dengue and what makes others resistant.

What spurred you to find a way to develop a new genome assembly?

I came from the field of Drosophila. The fly genome was sequenced in 2000 and it’s an incredible work of art. When I started working on the mosquito I thought, are you kidding me? I thought surely someone was going to do something about this genome. Eventually Ben Matthews and I realized nobody is dealing with this, so we pulled together this huge group and took care of it. None of us had reserves of money to put together a new genome project, so it was amazing that PacBio and other corporate sponsors and academics pulled together to get this done.

Did you ever imagine this kind of project could be launched by a tweet?

I still can’t believe we did it. It was so unlikely — I actually know nothing about genome sequencing. The genome has been out there for the last year and a half, and people have already gotten enormous use out of it. It’s really gratifying.

What’s next for your team and how you hope to use this new reference genome?

The genome is powering every single project in my lab. We study how the mosquito hunts people. The genome is seeping into everything — it’s helping us identify genes that allow mosquitoes to smell people, knock the genes out, and develop genetic tools. It’s so inspiring to be able to do all these things we couldn’t do before the genome came online.

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