Extensive analyses point to selection on ADCY8, a gene involved in long-term memory.
Many bird species undertake impressive migrations. Think of the Bar-tailed Godwit (Limosa lapponica), a small wader that can cover more than 29,000 kilometers in one year – travelling from Alaska to New Zealand and back. These achievements become even more mindboggling when you consider that several bird species are able to return to their exact breeding grounds. These birds must have a solid long-term memory. And indeed, a recent study in the journal Nature provided convincing evidence for selection on memory-related genes in long-distance migrants of the Peregrine Falcon (Falco peregrinus). Let’s have a look at the details of this exciting finding.
Migration Routes
First, the researchers used GPS-transmitters to track the migration of 41 Peregrine Falcons from several Russian locations. The resulting patterns pointed to five distinct migration routes which could be divided into short-distance (Kola and Kolguev) and long-distance (Yamal, Popigai, Lena and Kolyma) migration strategies. Attentive readers might have counted six locations even though I mention only five migration routes. That is because the short-distance migrants from Kola and Kolguev followed the same migration route and were thus clustered together.

Genetic Variants
Time for some genomic analyses. The researchers sequenced the genomes of 35 Peregrine Falcons and compared the genetic make-up of short-distance and long-distance migrants. This comparison uncovered signatures of 149 selective sweeps – targeting 37 genes – between the two groups. The most significant outlier in this analysis was the gene ADCY8. A closer look at this candidate gene revealed an interesting genetic locus with two alleles: C or T. All long-distance migrants possessed the T-variant, suggesting that there has been strong selection for this particular variant.
When the researchers inspected the DNA-letters surrounding this genetic variant, they recognized the sequence CGTCA, which is a binding motif for the transcription factor CREB. Transcription factors are proteins that control the expression of particular genes by binding with specific DNA sequences. The presence of this motif suggests that the expression of ADCY8 might be tightly regulated. And indeed, when the researchers quantified the expression levels of the different ADCY8-variants in brain tissue, they found that the T-variant was expressed at higher levels than the C-variant. Previous research has shown that this gene is involved in long-term memory by regulating the activity of other memory-related genes. The precise molecular details remain to be unraveled, but the researchers can already conclude:
The higher activity of ADCY8 that we identified in long-distance peregrine migrants may increase their long-term memory. Our analysis reveals a unique mutation that facilitates the binding of the transcription factor CREB1 to ADCY8, and fixation of this variation happened after the divergence of long-distance and short-distance populations. Our work thus not only reveals a causative gene that may explain migratory differences, but also provides a mechanistic basis for these differences.
References
Gu, Z., Pan, S., Lin, Z., Hu, L., Dai, X., Chang, J., … & Zhan, X. (2021). Climate-driven flyway changes and memory-based long-distance migration. Nature, 591(7849), 259-264.
Featured image: Peregrine Falcon (Falco peregrinus) © Mosharaf hossain ce | Wikimedia Commons