Selection on VPS13A linked to long-distance migratory behavior in a songbird

Animal migration demands an interconnected suite of physiological, behavioral, and neurological adaptations for individuals to successfully navigate and travel over long distances1-3. This trait complex is especially crucial for small songbirds whose migratory behaviors--like directionality and orientation--are innate4,5, rather than being learned as in many large, longer-lived birds. Identifying causal genes involved in these traits has been a central goal of migration ecology, and this endeavor has been furthered by genome-scale comparisons6. However, even the most successful studies of migration genetics have only achieved low resolution associations, identifying large chromosomal regions, across multiple haplotype blocks, that encompass hundreds of putatively causal genes7,8. Here we leverage the extreme genomic similarity among golden-winged (Vermivora chrysoptera) and blue-winged warblers (Vermivora cyanoptera)9 to identify a single gene--Vacuolar Protein Sorting 13 Homolog A (VPS13A)--that is associated with distinct differences in migration directionality to Central American (CA) versus South American (SA) wintering areas10. Moreover, we find significantly reduced sequence variation in this gene-region for SA wintering birds, and show this is the result of strong natural selection on this gene. In humans, VPS13A codes for chorein, and variants of this gene are associated with the neurodegenerative disorder chorea-acanthocytosis11. This new association provides the strongest gene-level linkage for avian migration directionality, and further interrogation of this gene will allow for a better understanding of its role in neuro-muscular processes across vertebrates.