京都大学 / 新制・課程博士 / 博士(医学) / 甲第24841号 / 医博第5009号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 朝長, 啓造, 教授 波多野, 悦朗, 教授 竹内, 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Studying genetic diversity in natural and domestic populations is of major importance in evolutionary biology. The recent advent of next generation sequencing (NGS) technologies has dramatically changed the scope of these studies, enabling researchers to study genetic diversity in a whole-genome context. This thesis details examples of studies using NGS data to: (i) characterize evolutionary forces shaping the genome of the Atlantic herring, (ii) detect the genetic basis of speciation and domestication in the rabbit, and, (iii) identify mutations associated with skeletal atavism in Shetland ponies. The Atlantic herring (Clupea harengus) is the most abundant teleost species inhabiting the North Atlantic. Herring has seasonal reproduction and is adapted to a wide range of salinity (3-35‰) throughout the Baltic Sea and Atlantic Ocean. By using NGS data and whole-genome screening of 20 populations, we revealed the underlying genetic architecture for both adaptive features. Our results demonstrated that differentiated genomic regions have evolved by natural selection and genetic drift has played a subordinate role. The European rabbit (Oryctolagus cuniculus) is native to the Iberian Peninsula, where two rabbit subspecies with partial reproductive isolation have evolved. We performed whole genome sequencing to characterize regions of reduced introgression. Our results suggest key role of gene regulation in triggering genetic incompatibilities in the early stages of reproductive isolation. Moreover, we studied gene expression in testis and found misregulation of many genes in backcross progenies that often show impaired male fertility. We also scanned whole genome of wild and domestic populations and identified differentiated regions that were enriched for non-coding conserved elements. Our results indicated that selection has acted on standing genetic variation, particularly targeting genes expressed in the central nervous system. This finding is consistent with the tame behavior present in domestic rabbits, which allows them to survive and reproduce under the stressful non-natural rearing conditions provided by humans. In Shetland ponies, abnormally developed ulnae and fibulae characterize a skeletal deformity known as skeletal atavism. To explore the genetic basis of this disease, we scanned the genome using whole genome resequencing data. We identified two partially overlapping large deletions in the pseudoautosomal region (PAR) of the sex chromosomes that remove the entire coding sequence of the SHOX gene and part of CRLF2 gene. Based on this finding, we developed a diagnostic test that can be used as a tool to eradicate this inherited disease in horses.