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Genetic Basis of Simple and Complex Traits with Relevance to Avian Evolution

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Genetic Basis of Simple and Complex Traits with Relevance to Avian Evolution Genetic basis of simple and complex traits with relevance to avian evolution Małgorzata Anna Gazda Doctoral Program in Biodiversity, Genetics and Evolution D Faculdade de Ciências da Universidade do Porto 2019 Supervisor Miguel Jorge Pinto Carneiro, Auxiliary Researcher, CIBIO/InBIO, Laboratório Associado, Universidade do Porto Co-supervisor Ricardo Lopes, CIBIO/InBIO Leif Andersson, Uppsala University FCUP Genetic basis of avian traits Nota Previa Na elaboração desta tese, e nos termos do número 2 do Artigo 4º do Regulamento Geral dos Terceiros Ciclos de Estudos da Universidade do Porto e do Artigo 31º do D.L.74/2006, de 24 de Março, com a nova redação introduzida pelo D.L. 230/2009, de 14 de Setembro, foi efetuado o aproveitamento total de um conjunto coerente de trabalhos de investigação já publicados ou submetidos para publicação em revistas internacionais indexadas e com arbitragem científica, os quais integram alguns dos capítulos da presente tese. Tendo em conta que os referidos trabalhos foram realizados com a colaboração de outros autores, o candidato esclarece que, em todos eles, participou ativamente na sua conceção, na obtenção, análise e discussão de resultados, bem como na elaboração da sua forma publicada. Este trabalho foi apoiado pela Fundação para a Ciência e Tecnologia (FCT) através da atribuição de uma bolsa de doutoramento (PD/BD/114042/2015) no âmbito do programa doutoral em Biodiversidade, Genética e Evolução (BIODIV). 2 FCUP Genetic basis of avian traits Acknowledgements Firstly, I would like to thank to my all supervisors Miguel Carneiro, Ricardo Lopes and Leif Andersson, for the demanding task of supervising myself last four years. In particular, I am indebted to Miguel for all effort, advice and patience introducing myself to bioinformatics and helping me to establish my interest in functional genomics. Secondly, I am very grateful to Leif Andersson, Joseph Corbo, Tracy Larson and Thomas Gilbert for hosting me at their laboratories for short-term scientific visits to experiment with other techniques and experience different scientific environments in diverse countries. I was very lucky to establish myself in EVOLGEN group in CIBIO and being part-time member of EVOCHANGE group. I would like to express my gratitude for having me last four years, all discussions, meetings, journal clubs. With special courtesy of Sandra Afonso for all trouble shooting in the lab and in the lab notebook, to Pedro Andrande and Cristiana Marques for exciting work done together, discussions and shared troubles with Portuguese bureaucracy. Finally to Jose Melo-Ferreira to be my unofficial co-supervisor, for having additional member of journal club and significantly committing towards my academic development. I feel privileged that I had an unique opportunity to work with all my collaborators, who significantly contributed not only to our manuscripts but also to my grow as a scientists, I especially would like to expressing thankfulness to Matthew Toomey, Joseph Corbo and Geoffrey Hill for exchanging countless number of emails, all great ideas, corrections and inside jokes. I am thankful Beatriz Lacerda and Markella Moraitou, who taught be me how to teach and supervise being such a great students. My work would not be possible without passion and curiosity of the generations of canary and pigeons breeders and fanciers. I thank for generous supply of samples and photographs for my projects. Words cannot describe how grateful I am for the best graphical abstract of my PhD to talented cartoonist Justyna Kierat. I am truly grateful to have such an amazing network of friends all around the world, who helped me to stay on my career path and quite often believed in me more than myself. 3 FCUP Genetic basis of avian traits Finally, the big thanks to my family, for allowing me to develop my interests, realize my crazy ideas and just being myself, especially to my parents Anna and Marek Gazda and my beloved sister Barbara Gazda-Lewandowska. My PhD in Porto inspired the name for my parent’s admired dog Porto. Finally yet importantly I would like to show appreciation Fundação para a Ciência e Tecnologia (FCT) for granting a PhD scholarship (PD/BD/114042/2015) therefore creating for me an opportunity to perform my doctoral research in Portugal. 4 FCUP Genetic basis of avian traits Abstract One of the 'grand challenges' in contemporary biology is to dissect the genetic basis of traits. The main aim of this thesis was to develop comprehensive links between traits with high importance for avian evolution and their genetic basis, using four different breeds of domestic birds (canaries and pigeons) as model systems. The studies were performed by resequencing whole genomes and establishing association between genotype and phenotype. Ultimately, the candidate genes were functionally tested to confirm the association and to provide detailed information about gene function. The first manuscript focuses on the evolution of traits associated with flying performance and spatial orientation. The molecular basis of the superior athletic and navigational capabilities of racing pigeons was investigated by using whole-genome and RNA sequencing data. Multiple signatures of positive selection distributed across the genome of racing pigeons were inferred, with a signature that stood out around the calcium/calmodulin dependent serine protein kinase gene (CASK). This gene was implicated in the formation of neuromuscular junctions. Surprisingly, not a single diagnostic allele was found between racing pigeons and other breeds and gene expression analysis between racing and non- racing breeds revealed modest differences in expression in brain and muscle tissue. Taken together, these results show that the unique suite of traits that enable fast flight, long endurance, and accurate navigation in racing pigeons, do not result from major loci acting as master switches but likely from a polygenic architecture that leveraged standing genetic variation available at the onset of the breed formation. After flying performance, one of the crucial traits for avian evolution is coloration. Yellow, orange, and red, carotenoid-based pigmentation is one of the pivotal drivers of avian diversity. Apart from producing an impressive range of colors and patterns, it has an important role in individual quality signaling and interactions. The carotenoid coloration is generated through the deposition of diet-derived pigments, but the mechanisms of carotenoid uptake and transport are not well understood. The next three research articles focused on genetic basis of carotenoid-based coloration and related traits in common canary (Serinus canaria). In the second article, we examined mechanisms of carotenoid uptake taking advantage of the white recessive canary breed, which carries an autosomal recessive mutation causing white plumage. Biochemical analysis revealed a genetic defect in carotenoid uptake. Detailed genomic analyses comparing the white recessive to yellow and red breeds of canaries showed that the white recessive allele is due to a splice-donor site mutation in the scavenger receptor B1 gene (SCARB1). Through functional assays, we further demonstrate that this mutation leads to a loss of function of the gene. 5 FCUP Genetic basis of avian traits Taken together, the results indicate that SCARB1 is an essential mediator of the expression of carotenoid-based coloration in birds and suggest a potential link between visual displays and lipid metabolism. In the third manuscript, we investigated the genetic basis of bare-part coloration driven by carotenoid pigments. The domestic urucum breed of canaries, that carries a mutation leading to bright red bills and legs, offered a unique opportunity to understand how leg and bill coloration evolves in birds. The causative locus was identified through a range of analyses on re-sequenced genomes in order to search for genotype-to-phenotype associations. A nonsynonymous mutation in the gene beta-carotene oxygenase 2 (BCO2), an enzyme involved in the cleavage and breakdown of carotenoids was identified. Protein structural models and in vitro functional assays confirmed dysfunction of carotenoid cleavage activity of mutant BCO2. Additionally, urucum canaries were characterized by a significant reduction in levels of carotenoid cleavage products (apocarotenoids) in retinal tissue indicating that BCO2 plays an important role in the pigmentation of the cone oil droplets, tuning sensitivity of photoreceptors. Our results further suggest that carotenoid-based bare-part coloration might be quickly gained, modified, or lost through simple switches in the enzymatic activity or regulation of BCO2 and this gene may be an important mediator in the evolution of bare-part coloration among bird species. Finally, the fourth manuscript provide insights into molecular mechanisms associated with the expression of sexual dichromatism (differences in coloration between males and females). These types of dimorphic traits are widely used to illustrate trade-offs between sexual and natural selection, yet, the molecular mechanisms through which birds evolve sex-specific coloration are poorly understood. The hybrid mosaic canary, a product of an interspecific cross between the sexually dichromatic red siskin and common monochromatic canaries, is a unique canary model characterized by pronounced differences in carotenoid-based coloration between males and females. Using a combination of genomic and transcriptomic approaches, we show dichromatism in mosaic canaries
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