Evidence for adaptive evolution towards high magnetic sensitivity of potential magnetoreceptor in songbirds

Abstract

Migratory birds possess remarkable accuracy in orientation and navigation, which involves various compass systems including the magnetic compass. Identifying the primary magnetosensor remains a fundamental open question. Cryptochromes (Cry) have been shown to be magnetically sensitive, specifically Cry4 shows enhanced magnetic sensitivity in migratory songbirds compared to resident species. Here, we investigate cryptochromes and their potential involvement in magnetoreception in a phylogenetic framework, integrating molecular evolutionary analyses with protein dynamics modeling. We base our analysis on 363 bird genomes and associate different selection regimes with migratory behaviour. We show that Cry4 is characterized by strong positive selection and high variability, typical characteristics of sensor proteins. We identify key sites that likely facilitated the evolution of a highly optimized sensory protein for night time compass orientation in songbirds and a potential functional shift or specialisation. Additionally, we show that Cry4 was lost in hummingbirds, parrots and Tyranni (Suboscines) and thus identified a natural comparative gene knockout, which can be used to test the function of Cry4 in birds. In contrast, the other two cryptochromes Cry1 and Cry2, were highly conserved in all species, indicating basal, non-sensory functions. Our results strengthen the hypothesised role of Cry4 as sensor protein in (night)-migratory songbirds.

Mutational Study of the Tryptophan Tetrad Important for Electron Transfer in European Robin Cryptochrome 4a

“…Phylogenetic analyses indicate no conservation of tyrosines in migratory species; however, only one migratory passerine was identified without the tyrosine but instead a histidine at position 319. 65 The test for positive selection (omega >1) through the empirical Bayes (NEB) was not significant, with a posterior probability of 0.0 for the 319 site. The sequence conservation at the tryptophan sites reflected in Figure 2A−D is also reflected by the strong purifying selection acting on the four sites (see Figure 3), where omega is 0.067 and the empirical Bayes (NEB) posterior probability is 0.0 when testing for an omega value above one for the four tryptophan sites.…”

“…The higher variability of the Y319 site is reflected by an omega value of 1.00, indicating that this site is evolving neutrally. Phylogenetic analyses indicate no conservation of tyrosines in migratory species; however, only one migratory passerine was identified without the tyrosine but instead a histidine at position 319 …”

“…Phylogenetic analyses indicate no conservation of tyrosines in migratory species; however, only one migratory passerine was identified without the tyrosine but instead a histidine at position 319. 65 …”

Structural Rearrangements of Pigeon Cryptochrome 4 Undergoing a Complete Redox Cycle

“…The importance of the EEE motif motion is further strengthened by the fact that the motif is evolutionarily conserved throughout different bird species (European robin, zebra finch, and chicken) as shown from sequence alignments performed earlier. 44,51 Lastly, the distances between FAD and the different tryptophans included in the electron transfer cascade were studied. These distances influence the formation and lifetime of the formed spin-correlated radical pair and have previously been studied on the shorter all-atom time scale.…”

“…The importance of the EEE motif motion is further strengthened by the fact that the motif is evolutionarily conserved throughout different bird species (European robin, zebra finch, and chicken) as shown from sequence alignments performed earlier. 44 , 51 …”