Unraveling the evolutionary secrets behind the world's only flightless cormorant and its surprising connection to human genetic disorders
In the remote Galapagos Islands, an archipelago that served as a living laboratory for Charles Darwin's theory of evolution, there lives a biological puzzle: the Galapagos cormorant (Phalacrocorax harrisi), the only one of 40 cormorant species that cannot fly 5 .
Only cormorant species that cannot fly
Wing size compared to flying relatives
With stunted wings just one-third the size needed for flight and a body that dwarfs its airborne relatives, this unique bird has long fascinated scientists 5 . For evolutionary biologists, a pressing question remained: what genetic changes could have led to the loss of such a fundamental avian trait as flight?
Recent research has unraveled this mystery, revealing that the cormorant's flightlessness stems from genetic mutations affecting cilia - tiny, hair-like structures on cells that play a crucial role in bone development 2 4 .
Intriguingly, when these same genes are mutated in humans, they cause skeletal disorders known as ciliopathies, characterized by shortened limbs and narrowed chests - features mirroring the cormorant's stunted wings and reduced breastbone 4 . This discovery not only illuminates a classic example of evolution but also opens new pathways for understanding human genetic disorders.
Mutations that hinder flight might enhance other survival abilities, such as swimming.
The only cormorant species that cannot fly, with unique genetic adaptations.
In the absence of predators, flight-hindering mutations accumulate without negative consequences.
"For Darwin, just by looking at these changes, inferred the process of evolution by natural selection," says senior study author Leonid Kruglyak, professor of human genetics at UCLA 4 . "We now have sophisticated genetic tools to reexamine these classic examples and uncover what happened at the molecular level."
Unlike ostriches and kiwis that diverged over 50 million years ago, the Galapagos cormorant's recent divergence provides a clearer window into evolutionary mechanisms.
To pinpoint the genetic basis of flightlessness, an international team of scientists embarked on an extensive genomic analysis 1 . They sequenced and assembled the complete genomes of the flightless Galapagos cormorant and three flying cormorant species: the double-crested cormorant, the neotropical cormorant, and the pelagic cormorant 1 3 .
The researchers developed a comparative and predictive genomics approach to identify genetic variants unique to the flightless cormorant that likely contributed to its dramatic anatomical changes 3 . They analyzed thousands of protein-coding genes, looking specifically for mutations that would alter protein function 1 .
The Galapagos cormorant has extremely low genetic diversity with only 0.00685% of sites being heterozygous in the sequenced individual 1 .
Approximately 1,500 individuals with multiple historical population bottlenecks that may have accelerated the fixation of flightlessness mutations 1 .
| Species | Flight Ability | Role in Study | Genetic Diversity |
|---|---|---|---|
| Galapagos cormorant (P. harrisi) | Flightless | Primary subject of investigation | Lowest (0.00685% heterozygous SNPs) |
| Double-crested cormorant (P. auritus) | Flighted | Closest relative for comparison | Higher than P. harrisi |
| Neotropical cormorant (P. brasilianus) | Flighted | Close relative for comparison | Higher than P. harrisi |
| Pelagic cormorant (P. pelagicus) | Flighted | Outgroup for evolutionary analysis | Higher than P. harrisi |
The research team discovered that variants most likely to alter protein function in the Galapagos cormorant were significantly enriched in genes associated with human skeletal ciliopathies 3 . These included genes such as Ofd1, Evc, Wdr34, and Ift122, all crucial for the proper formation and function of cilia 3 .
| Gene | Variant Type | Normal Function | Proposed Effect in Cormorants |
|---|---|---|---|
| CUX1 | 4-amino acid deletion in regulatory domain | Transcription factor regulating limb growth and cilia-related genes | Impaired chondrogenic differentiation and cilia gene regulation |
| IFT122 | Missense mutation in highly conserved region | Controls development of cilia across animal kingdom | Disrupted ciliary function affecting skeletal development |
| Other cilia-related genes (Ofd1, Evc, Wdr34) | Various function-altering variants | Various roles in cilia formation and function | Combined impact on bone growth regulation |
To confirm that these genetic variants actually caused functional changes, the team designed innovative cross-species experiments 1 3 . Since working with cormorants in laboratory settings is challenging, they turned to two established model organisms: the nematode worm C. elegans and mouse chondrogenic (cartilage-forming) cell lines 3 .
Researchers first identified a specific missense mutation in the IFT122 gene of Galapagos cormorants—a mutation in a region that remains constant across other species .
Using CRISPR gene-editing technology, the team modified the C. elegans version of IFT122 to match the cormorant's variant .
After introducing the cormorant's genetic signature into the worms, researchers observed that their cilia stopped working correctly, confirming the mutation's functional impact .
For the CUX1 gene, which had a unique 4-amino acid deletion in the cormorant, researchers deleted the same segment in the mouse version of CUX1 and found that cartilage-making cells divided more slowly .
Additional experiments showed that the cormorant's CUX1 variant impaired its ability to promote chondrogenic differentiation and upregulate cilia-related genes 3 .
Genome assembly from Illumina sequences
Prediction of variant effects on protein function
Precise gene editing in model organisms
In vivo testing of ciliary function
The cross-species experiments demonstrated that:
These findings provided functional validation that the identified genetic variants were responsible for the flightless cormorant's unique characteristics.
This research provides a fascinating window into how major evolutionary changes can occur through accumulated mutations in key developmental pathways 3 . The findings suggest that the flightless cormorant's stunted wings resulted from variants affecting cilia structure and function, leading to skeletal changes that mirror human ciliopathies 1 4 .
"Loss of flight is something that has taken place in birds frequently," notes Kruglyak 2 4 . "There's a pretty rich field trying to understand how all these changes happen and whether common trajectories exist between species."
Future research will explore whether other flightless birds like ostriches and kiwis share similar genetic mutations with the Galapagos cormorant 2 4 .
The study opens potential avenues for medical research. Understanding how the Galapagos cormorant tolerates mutations that would cause severe disease in humans might provide insights into treating skeletal ciliopathies 7 .
As Burga notes, "Can we find the same genes that have been affected in other animals, including primates?" 7
The flightless cormorant of the Galapagos, once a puzzle that captivated Darwin, continues to inspire scientific discovery, demonstrating how studying evolutionary oddities in nature can illuminate fundamental biological processes relevant to human health and development.