Genomic analyses of migratory divides in the willow warbler

In many species of birds juveniles migrate independently of experienced adults and thus have to rely on innate information about migratory routes and wintering area. This information is encoded as a set of inherited migratory directions and a timing schedule that provides information on when and how far to migrate. Apart from these remarkable behavioral adaptations, migration also requires several morphological, physiological and immunological adaptations. Although many migratory traits have been demonstrated to have strong heritable basis, virtually nothing is known about the specific genes underlying them. The lack of known migration genes limits a deeper understanding of the mechanistic processes and evolution of migration. In this thesis, I use the willow warbler Phylloscopus trochilus to explore the molecular genetics of migration. The willow warbler occurs with two subspecies in Europe. Ringing recoveries and stable isotopes have demonstrated that the subspecies use different migratory routes and wintering areas. An extremely low genetic differentiation and otherwise similar phenotypes, suggest that most of the genetic differences are likely to be involved in adaptations to the different migratory strategies of the subspecies. Here I use several different high throughput molecular techniques to identify differences between the subspecies. I find that genetic differences between the willow warbler subspecies are clustered in three divergent regions on different chromosomes, which each span several million base pairs and are comprised of numerous coding genes. The regions show restricted recombination between the warbler subspecies and could be maintained by inversions. A region on chromosome 3 is not specifically associated with the subspecies, but appears to be involved in adaptations to high altitude and latitude environments. The two other chromosome regions contain subspecies-specific variation. In a region on chromosome 1, genetic differentiation peaks close to the gene FOXO1, which is important in the formation of fat cells and gluconeogenesis. In the other region, which is located on chromosome 5, there is an enrichment of gene functions associated with fatty acid genes. The functions of these genes suggest that the two chromosome regions could be associated with adaptations to fuelling. Future studies on genetics of migration would benefit from assembled genomes that could be used as a basis for several high-resolution molecular techniques that could detect more localized differences and provide higher resolution of divergent chromosome regions. There is also a need to associate particular genes or chromosome regions with particular phenotypes. This would be aided by efficient and precise high-throughput phenotyping for example by new tracking technologies or controlled behavioral experiments in laboratories

Migration direction in a songbird explained by two loci

Migratory routes and remote wintering quarters in birds are often species and even population specific. It has been known for decades that songbirds mainly migrate solitarily, and that the migration direction is genetically controlled. Yet, the underlying genetic mechanisms remain unknown. To investigate the genetic basis of migration direction, we track genotyped willow warblers Phylloscopus trochilus from a migratory divide in Sweden, where South-West migrating, and South-East migrating subspecies form a hybrid swarm. We find evidence that migration direction follows a dominant inheritance pattern with epistatic interaction between two loci explaining 74% of variation. Consequently, most hybrids migrate similarly to one of the parental subspecies, and therefore do not suffer from the cost of following an inferior, intermediate route. This has significant implications for understanding the selection processes that maintain narrow migratory divides

Repeated genomic signatures of adaptation to urbanisation in a songbird across Europe

Urbanisation is currently increasing worldwide, and there is now ample evidence of phenotypic changes in wild organisms in response to this novel environment, but the extent to which this adaptation is due to genetic changes is poorly understood. Current evidence for evolution is based on localised studies, and thus lacking replicability. Here, we genotyped great tits (Parus major) from nine cities across Europe, each paired with a rural site, and provide evidence of repeated polygenic responses to urban habitats. In addition, we show that selective sweeps occurred in response to urbanisation within the same genes across multiple cities. These genetic responses were mostly associated with genes related to neural function and development, demonstrating that genetic adaptation to urbanisation occurred around the same pathways in wildlife populations across a large geographical scale.Competing Interest StatementThe authors have declared no competing interest

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

PMCID: PMC3480949This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Continent-wide genomic signatures of adaptation to urbanisation in a songbird across Europe

Urbanisation is increasing worldwide, and there is now ample evidence of phenotypic changes in wild organisms in response to this novel environment. Yet, the genetic changes and genomic architecture underlying these adaptations are poorly understood. Here, we genotype 192 great tits (Parus major) from nine European cities, each paired with an adjacent rural site, to address this major knowledge gap in our understanding of wildlife urban adaptation. We find that a combination of polygenic allele frequency shifts and recurrent selective sweeps are associated with the adaptation of great tits to urban environments. While haplotypes under selection are rarely shared across urban populations, selective sweeps occur within the same genes, mostly linked to neural function and development. Collectively, we show that urban adaptation in a widespread songbird occurs through unique and shared selective sweeps in a core-set of behaviour-linked genes

The human secretome

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood

Interactions between Plasma Levels of 25-Hydroxyvitamin D, Insulin-Like Growth Factor (IGF)-1 and C-Peptide with Risk of Colorectal Cancer

Background: Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor. Methods: Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively. Results: Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive = 0.06, multiplicative = 0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH)D was low (OR = 1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR = 1.15, 95% CI: 0.74 to 1.77, p(interaction): additive = 0.004; multiplicative = 0.04). Conclusion: The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements