How the Galápagos cormorant got its tiny wings

COLD SPRING HARBOR, N.Y. — Garbled signals from cellular antennas may have grounded the Galápagos cormorant.

Galápagos cormorants (Phalacrocorax harrisi) are the only cormorant species with wings too small to lift the birds’ large bodies off the ground. Broken primary cilia —antennas that cells need to receive key developmental messages — left the cormorants with stunted wings, UCLA evolutionary biologist Alejandro Burga suggested May 12 at the Biology of Genomes meeting.

Burga and colleagues compared DNA of flightless Galápagos cormorants with that of their close relatives, including double-crested cormorants (Phalacrocorax auritus), which have large wings and can fly. The researchers found more than 23,000 differences in more than 12,000 genes. Those changes have occurred within the last 2 million years, a short time by evolutionary standards.
Many of those genes probably have nothing to do with wing size. So Burga and colleagues narrowed down which genes might have had the biggest effect on cormorant evolution using a computer program that predicts whether a change in a gene will affect its function. Genes that have mutations that damage function may have big evolutionary consequences. Of the genes predicted to have altered function, the researchers selected the 3.3 percent that have changed most drastically in Galápagos cormorants.

To determine what these genes do, Burga examined whether any of the human versions of these genes cause problems when they are mutated in people. Eight of the banged-up genes were associated with limb defects caused by faulty primary cilia, hairlike structures that grow from cells. The cilia receive signals important for the development and proper functioning of cells (SN: 11/3/12, p.16). In people, genetic mutations that damage primary cilia lead to a wide variety of diseases, including developmental defects.

Normal versions of those eight genes are necessary for primary cilia to pick up signals sent by an important protein called hedgehog. Those genes are so crucial for normal development that evolution has not allowed them to change much in 300 million years. Three other genes that are mutated in the flightless cormorants affect other aspects of the primary cilia. In people, mutant versions of all 11 cilia genes can cause small limbs, extra fingers and short ribs, Burga said.

It wasn’t clear whether the cilia defects were the primary cause of the birds’ flightlessness. So Burga further narrowed his focus to 10 of the altered Galápagos cormorant genes predicted by the computer program to give the biggest functional and evolutionary disadvantages. Those genes would be the most important wing shrinkers, Burga and his colleagues reasoned.

One of those top 10 candidates is a gene called CUX1. The protein it produces helps turn on other genes. Vertebrates from primitive coelacanths to people have nearly identical versions of the gene. But in flightless cormorants, four amino acids have been lost from the protein, suggesting that it can no longer do its job or does it poorly. In chickens, a defective form of CUX1 can shrink wings. That finding indicates the Galápagos cormorant’s altered form of CUX1 might also make wings smaller because it fails to turn on limb growth genes.
Many researchers would have left the story at that point, says Ludovic Orlando, an evolutionary biologist at the University of Copenhagen. “But they didn’t simply stop there,” Orlando says. “They made an effort to validate their findings. It’s unusual.”

Burga and colleagues wondered whether CUX1 and the primary cilia changes were related. The researchers injected cells used to mimic skeletal development in lab dishes with the normal vertebrate version of CUX1. Activity levels of two cilia genes rose by about 50 percent. That is evidence that CUX1 normally helps to regulate activity of primary cilia genes.

But the Galápagos cormorant version of CUX1 barely budged activity of the cilia genes. It also was not as good at stimulating growth and development of bone cells as the normal version, the researchers found. Those findings strengthen the case that CUX1 and primary cilia together were involved in shrinking the flightless fowl’s wings.

It’s still a mystery why Galápagos cormorants have normal size legs, Burga said.