Millions of migratory birds occupy seasonally favourable breeding grounds in the Arctic 1 , but we know little about the formation, maintenance and future of Arctic bird migration routes and genetic determinants of migratory distance. Here, we established a continental-scale migration system, satellite tracking 56 peregrine falcons (Falco peregrinus) from six Eurasian Arctic breeding populations and resequencing 35 genomes from four of these. Different breeding populations used five migration routes across Eurasia, likely formed by longitude and latitude breeding ground shifts during the LGM-Holocene transition. Contemporary inter-route environmental divergence appears to maintain distinct migration routes. We found that the novel gene ADCY8 was associated with population-level migratory distance differences. We elucidated its regulatory mechanism and found the most likely selective agent for this divergence was long-term memory. Global warming is predicted to influence migration strategies and diminish breeding ranges of Eurasian Arctic peregrines. Harnessing ecological interactions and evolutionary processes to study climate-driven changes in migration can facilitate the conservation of migratory birds.

Low oxygen and temperature pose key physiological challenges for endotherms living on the Qinghai-Tibetan Plateau (QTP). Molecular adaptations to high-altitude living have been detected in the genomes of Tibetans, their domesticated animals and a few wild species, but the contribution of transcriptional variation to altitudinal adaptation remains to be determined. Here we studied a top QTP predator, the saker falcon, and analysed how the transcriptome has become modified to cope with the stresses of hypoxia and hypothermia. Using a hierarchical design to study saker populations inhabiting grassland, steppe/desert and highland across Eurasia, we found that the QTP population is already distinct despite having colonized the Plateau <2000 years ago. Selection signals are limited at the cDNA level, but of only seventeen genes identified, three function in hypoxia and four in immune response. Our results show a significant role for RNA transcription: 50% of upregulated transcription factors were related to hypoxia responses, differentiated modules were significantly enriched for oxygen transport, and importantly, divergent EPAS1 functional variants with a refined co-expression network were identified. Conservative gene expression and relaxed immune gene variation may further reflect adaptation to hypothermia. Our results exemplify synergistic responses between DNA polymorphism and RNA expression diversity in coping with common stresses, underpinning the successful rapid colonization of a top predator onto the QTP. Importantly, molecular mechanisms underpinning Correspondence: Xiangjiang Zhan, Fax: +86 (0)1064807099; E-mail: zhanxj@ioz.ac.cn 1 These two authors contributed equally to the paper. highland adaptation involve relatively few genes, but are nonetheless more complex than previously thought and involve fine-tuned transcriptional responses and genomic adaptation.

Background: Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, and for the guanaco and vicuña (their putative wild progenitors), compare these with the published alpaca genome, and resequence seven individuals of all four species to better understand domestication and introgression between the llama and alpaca. Results: Phylogenomic analysis confirms that the llama was domesticated from the guanaco and the alpaca from the vicuña. Introgression was much higher in the alpaca genome (36%) than the llama (5%) and could be dated close to the time of the Spanish conquest, approximately 500 years ago. Introgression patterns are at their most variable on the X-chromosome of the alpaca, featuring 53 genes known to have deleterious X-linked phenotypes in humans. Strong genome-wide introgression signatures include olfactory receptor complexes into both species, hypertension resistance into alpaca, and fleece/fiber traits into llama. Genomic signatures of domestication in the llama include male reproductive traits, while in alpaca feature fleece characteristics, olfaction-related and hypoxia adaptation traits. Expression analysis of the introgressed region that is syntenic to human HSA4q21, a gene cluster previously associated with hypertension in humans under hypoxic conditions, shows a previously undocumented role for PRDM8 downregulation as a potential transcriptional regulation mechanism, analogous to that previously reported at high altitude for hypoxia-inducible factor 1α. Conclusions: The unprecedented introgression signatures within both domestic camelid genomes may reflect post-conquest changes in agriculture and the breakdown of traditional management practices.

The Qinghai-Tibet Plateau (QTP), possesses a climate as cold as that of the Arctic, and also presents uniquely low oxygen concentrations and intense ultraviolet (UV) radiation. QTP animals have adapted to these extreme conditions, but whether they obtained genetic variations from the Arctic during cold adaptation, and how genomic mutations in non-coding regions regulate gene expression under hypoxia and intense UV environment, remain largely unknown. Here, we assemble a high-quality saker falcon genome and resequence populations across Eurasia. We identify female-biased hybridization with Arctic gyrfalcons in the last glacial maximum, that endowed eastern sakers with alleles conveying larger body size and changes in fat metabolism, predisposing their QTP cold adaptation. We discover that QTP hypoxia and UV adaptations mainly involve independent changes in non-coding genomic variants. Our study highlights key roles of gene flow from Arctic relatives during QTP hypothermia adaptation, and cis-regulatory elements during hypoxic response and UV protection.

Alternatively spliced transcript isoforms are thought to play a critical role for functional diversity. However, the mechanism generating the enormous diversity of spliced transcript isoforms remains unknown, and its biological significance remains unclear. We analyzed transcriptomes in saker falcons, chickens, and mice to show that alternative splicing occurs more frequently, yielding more isoforms, in highly expressed genes. We focused on hemoglobin in the falcon, the most abundantly expressed genes in blood, finding that alternative splicing produces 10-fold more isoforms than expected from the number of splice junctions in the genome. These isoforms were produced mainly by alternative use of de novo splice sites generated by transcription-associated mutation (TAM), not by the RNA editing mechanism normally invoked. We found that high expression of globin genes increases mutation frequencies during transcription, especially on nontranscribed DNA strands. After DNA replication, transcribed strands inherit these somatic mutations, creating de novo splice sites, and generating multiple distinct isoforms in the cell clone. Bisulfate sequencing revealed that DNA methylation may counteract this process by suppressing TAM, suggesting DNA methylation can spatially regulate RNA complexity. RNA profiling showed that falcons living on the high Qinghai–Tibetan Plateau possess greater global gene expression levels and higher diversity of mean to high abundance isoforms (reads per kilobases per million mapped reads ≥18) than their low-altitude counterparts, and we speculate that this may enhance their oxygen transport capacity under low-oxygen environments. Thus, TAM-induced RNA diversity may be physiologically significant, providing an alternative strategy in lifestyle evolution.

The original version of this Article contained an error in the Results subsection "Hybridization with Arctic gyrfalcons facilitated sakers' adaptation to cold extremes", which incorrectly read 'To do this, we applied an ABBA-BABA model 37 , and found five outstanding genomic islands (>200 Kb) on the five chromosomes (Chr 1, 3, 5, 8 and 16) exhibiting adaptive introgression signatures (top 1% D = 0.73, top 1% f d = 0.70) (Fig. 2b; Supplementary Fig. 10) which were much longer than the expected length of fragments ( 26.6 Kb) from incomplete lineage sorting (ILS; "Methods").' The correct version states '26.0 Kb' in place of '26.6 Kb'. The original version of this Article contained an error in the Methods subsection "De novo assembly of the saker falcon genome", which incorrectly read 'We assembled a chromosomelevel reference genome of an adult female saker falcon (aQTP saker rescued by XiningWildlife Park) (2n = 56) using a multi-platform sequencing strategy (PacBio, Illumina, Bionano)'. The correct version states '2n = 52' in place of '2n = 56'.The original version of this Article contained an error in the Methods subsection "Estimation of adaptively introgressed signals and discrimination from ILS", which incorrectly read 'In our case, we set the parameters according to the fastsimcoal2 result: t = 3181 generations (21 ka), m = 0.23 (the minimum introgression rate in Frappe result), r = 2E−08 (assuming that each of the 26 chromosomes experiences on average one crossover per generation 123 ). When the P was larger than 0.05, the fragments shorter than 26.6 Kb were considered as those that may be influenced by ILS. Accordingly, fragments that longer than 26.6 Kb were considered from introgression.' The correct version states 'm = 0.213' in place of 'm = 0.23', 'fragments shorter than 26.0 Kb' in place of 'fragments shorter than 26.6 Kb', and 'fragments longer than 26.0 Kb' in place of 'fragments that longer than 26.6 Kb'.These have been corrected in both the PDF and HTML versions of the Article.

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