How hummingbirds power their rapid flight

The hummingbird is the smallest in the world. They can actually hover mid-air, and uniquely among birds, can fly backwards and upside-down. The quickest of them beats its wings more than eighty times per second. All this aerial acrobatics requires some unique tricks of energy and metabolism - and Phil Sansom heard from Ariel Gershman at the Johns Hopkins School of Medicine, who has been trying to figure out what in their genes makes all this possible…

Ariel - We're really interested in something that hummingbirds do called metabolic flux. They are able to maintain this extremely high metabolism, and extremely high blood sugar, that for most humans would be considered as diabetes; but hummingbirds are able to do this without getting any of the ailments associated with diabetes, like blindness, and kidney disease, and all of these other problems that humans who maintain this persistently high blood sugar often experience.

Phil - What's the flux part of that? Is it flux like changing really quickly?

Ariel - The flux is just this rapid shift that they're able to do. So when hummingbirds are eating, they're eating sugar from nectar, and they're able to use the sugar almost entirely to fuel their metabolism, or how they break down that sugar to make energy. But then once they stop feeding, they have to rapidly switch their metabolism to be able to use this fat that they store in their body to then be able to get energy, and power this extremely expensive hovering flight that they're able to do. And so if they weren't able to switch this metabolism so quickly, from their fed state to their fasted state, then they wouldn't be able to continue flying.

Phil - Oh my God, it almost sounds like one of those animals that hibernates in winter and then does all their eating in the summer, but over the course of what, minutes?

Ariel - Yeah. Over the course of 30 minutes is how quickly they're able to switch this fed to fasted metabolism.

Phil - What exactly are you doing to look into this metabolic flux, as you called it?

Ariel - We first had to actually sequence and put together their entire genome. And once we had the whole genome together, we then had to figure out where genes in the genome are. Because only about 1% of the genome actually codes for genes that end up making proteins. And then what we did was we sequenced all of the hummingbird RNA. If you can imagine. the genome is kind of like the blueprint for how to build the organism, whereas the RNA is more like what's actually being made to allow the organism to survive and persist.

Phil - How are you doing this here then, with both the DNA and the RNA?

Ariel - What we mainly focus on is called long read sequencing. Some people call it third generation sequencing. The typical, or the gold standard of DNA sequencing, is this second generation sequencing right now. And in second generation sequencing, it's extremely accurate, but we're only getting small pieces of DNA at a time. Where in third generation sequencing, we're actually sequencing these really, really long molecules of DNA. And if you can imagine, when you're putting together a puzzle, it's a lot easier to put together a puzzle with less pieces that are bigger than a puzzle with more pieces that are smaller. However we lose a little bit of the accuracy with long read sequencing, so it's more likely that there will be mistakes.

Phil - Do you do anything to compensate for that?

Ariel - Yeah, we do. Once we have the entire structure from the long read data we go in and we correct it with the accurate short read data. This is a process that in the field we call hybrid genome assembly.

Phil - Wow. And just for context, how big is the job? How many genes does a hummingbird have?

Ariel - Oh, a hummingbird has around 20 to 30,000 genes. Not that much different than a human actually.

Phil - That's, yeah, quite a few genes to get through...

Ariel - Yeah. And it's actually not even the region of the genome that codes for genes that's the hard part; it's really the rest of the genome, that we don't really know a lot about what it does, that's actually the hard part for genome assembly, because a lot of the genome is made up of repetitive DNA. And if you can imagine, if you have the same puzzle piece that fits in multiple locations, you really don't know where it actually goes.

Phil - And what do you do in that situation?

Ariel - The longer reads actually really help us out a lot there. Because when we have the repeat, if we can get the information on either side of it we can anchor it to the right region of the genome.

Phil - These hummingbirds, then, you're giving them a nice big meal, then taking a bunch of blood to get all their DNA and RNA, or what?

Ariel - We're actually taking their liver and their muscle tissue. So those are the really important metabolic tissues.

Phil - With all this incredible third generation sequencing, what are you finding in there?

Ariel - Wow. I wish I had like the cure to diabetes or something crazy... but we're finding a lot of differences in expression in thyroid hormone, which is along the lines of what we expected. What we're really looking for and hoping to find is these glucose transporters. Not a lot is really known about how glucose, sugar, actually gets into the hummingbird cells and how it happens so quickly. Hummingbirds don't seem to have a lot of these genes that humans have that allow sugar to enter our cells. So how was it entering in hummingbirds? We don't know yet. And we're really hoping to figure that out.

Phil - Do you have any personal favourite theories at the moment?

Ariel - I think that this glucose transporter that we're looking for that we don't think is present in hummingbirds... I think that it might be there, it's just that it's in a region of the genome that's so repetitive that previous people who have studied it, haven't been able to find it because of this repeat problem.