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Dissecting genotype-phenotype relationships using high-throughput genomics and carefully selected study populations

Final Report Summary - BATESON (Dissecting genotype-phenotype relationships using high-throughput genomics and carefully selected study populations)

The aim of the Bateson project has been study genotype-phenotype relationships using carefully selected study populations. This has been accomplished by studying a natural population, the Atlantic herring, and several domestic animals, rabbit, chicken and pig. The project has accomplished much more than initially planned since the costs for whole genome sequencing drastically has dropped during the project period.
The Atlantic herring is one of the world’s most abundant vertebrates, and the estimated population size in the Atlantic Ocean and the Baltic Sea is on the order of a trillion (1012) individuals! The Atlantic herring constitutes one of the world’s five most important marine fisheries and herring has been a critical food resource in Northern Europe throughout human history. The project has established the Atlantic herring as a new model organism for genome biology. The unique features of this species are an enormous population size and the genetic differentiation between subpopulations is largely due to natural selection because the effects of random genetic drift are minute. The Bateson project has established a high-quality draft assembly of the herring genome and a new further improved 2.0 version of the assembly is in preparation. We have carried out whole genome sequencing of 25 populations of Atlantic herring. This has resulted in the identification of hundreds of genes associated with ecological adaptation to the brackish Baltic Sea, the herring is one of the few marine fish that is able to reproduce throughout the entire Baltic Sea. We have also identified about 100 genes associated with the timing of reproduction, and our hypothesis is that a subset of these, including the TSHR gene, is involved in photoperiodic regulation of reproduction. To reproduce at a time when the chance of survival of the progeny is optimal is crucial in nature. The Bateson project has established the herring as a model to further explore the genetic mechanisms underlying variation in this phenotype. We have also provided conclusive evidence that changes in protein-coding sequences as well as changes in gene regulation have contributed to adaptation in the Atlantic herring. Finally, we expect that the Bateson project will lead to practical applications since the rich collection of genetic markers we have reported can be used for improved assessment of the abundance of different stocks of herring and form a basis for a more sustainable herring fishery.
The most important contribution of the Bateson project to studies of domestic animals has been our analysis of the genetic basis for rabbit domestication. The rabbit is particularly well suited for such an analysis because (i) rabbit domestication is a recent event, it was initiated only about 1400 years ago, (ii) we know exactly where it took place, Southern France and (iii) the region where domestication happened is still densely populated by wild rabbits that can be studied. In this study we carried out whole genome sequencing of many populations of wild and domestic rabbits and searched for consistent genetic differences between the two groups. The analysis demonstrated (i) that rabbit domestication has a highly polygenic background, (ii) there are shifts in gene frequencies at many loci rather than fixed differences at a few “domestication genes” and (iii) genetic changes in evolutionary conserved, non-coding sequences located in the vicinity of genes with a role in brain and neuronal development have been particularly important. We propose that these conclusions apply to other domestic animals as well (e.g. dog, chicken and pig) but it has been much more challenging to explore this in other domestic animals due to their complex demographic history.