Kruglyak wanted to know why this bird couldn’t take to the skies. Specifically, as a geneticist, he wanted to know what genetic changes had grounded it. When he got back to his lab, he reached out to a research team that had collected blood samples from 223 flightless cormorants—almost a quarter of the total endangered population. He and his own team used these samples to sequence the cormorant’s genome, then compared its DNA to that of three other cormorant species, looking for mutations that are unique to the flightless one, and that are likely to alter its genes in important ways.
They found a long list of affected genes. Many of these, when mutated in humans, distort the growth of limbs, resulting in extra fingers, missing digits, and other similar conditions. Some of them are also responsible for a group of rare inherited disorders called ciliopathies, where cilia—small hair-like structures on the surface of cells—don’t develop correctly. Cells use cilia to exchange signals and coordinate their growth. If these hairs don’t form correctly, many body parts don’t develop in the usual way. In particular, some people with ciliopathies grow up with short limbs and small ribcages—a striking parallel with the stunted wings and small breastbone of the flightless cormorant.
All of this is circumstantial. It suggests, but doesn’t confirm, that the cormorant’s flightless wings might result of a kind of benign ciliopathy. To make a stronger case, Alejandro Burga, a member of Kruglyak’s team, focused his attention on a couple of genes. One of them—IFT122—controls the development of cilia across the animal kingdom. The Galapagos cormorant has a single mutation in a part of the gene that is always the same in other species.
The ideal experiment would be to alter the same gene in another species of cormorant, to see if they develop shorter wings. But cormorants aren’t exactly easy to work with in a lab, so Burga turned to a more amenable animal: the tiny roundworm, C. elegans. He used the gene-editing technique called CRISPR to change the worm’s version of IFT122 to match the cormorant’s. And sure enough, its cilia stopped working correctly.
Burga also focused on another gene called CUX1, which controls the activity of many other cilia-building genes. It’s especially active in the cartilage-making cells that lay the foundations for our skeletons. And here too, the cormorant has an unusual change—it’s missing a 12-letter stretch of DNA that’s present in almost all other back-boned animals. And when Burga deleted this same stretch from the mouse version of CUX1, the cartilage-making cells divide more slowly.
All of these experiments paint a consistent picture. By building up mutations in several genes, the ancestors of the Galapagos cormorant changed the workings of its cilia and so altered the growth of the cells that form its skeleton. The result: shorter wings, smaller breastbones, and the loss of flight.