TY - THES AB - In evolve and resequence experiments, a population is sequenced, subjected to selection and then sequenced again, so that genetic changes before and after selection can be observed at the genetic level. Here, I use these studies to better understand the genetic basis of complex traits - traits which depend on more than a few genes. In the first chapter, I discuss the first evolve and resequence experiment, in which a population of mice, the so-called "Longshanks" mice, were selected for tibia length while their body mass was kept constant. The full pedigree is known. We observed a selection response on all chromosomes and used the infinitesimal model with linkage, a model which assumes an infinite number of genes with infinitesimally small effect sizes, as a null model. Results implied a very polygenic basis with a few loci of major effect standing out and changing in parallel. There was large variability between the different chromosomes in this study, probably due to LD. In chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency based summary statistic, giving an equation based on the initial allele frequencies, average pairwise LD, and the first four moments of the haplotype block copy number distribution. I describe this distribution by referring back to the founder generation. I then demonstrate how to infer selection via a maximum likelihood scheme on the example of a single locus and discuss how to extend this to more realistic scenarios. In chapter three, I discuss the second evolve and resequence experiment, in which a small population of Drosophila melanogaster was selected for increased pupal case size over 6 generations. The experiment was highly replicated with 27 lines selected within family and a known pedigree. We observed a phenotypic selection response of over one standard deviation. I describe the patterns in allele frequency data, including allele frequency changes and patterns of heterozygosity, and give ideas for future work. AU - Belohlavy, Stefanie ID - 11388 SN - 978-3-99078-018-3 TI - The genetic basis of complex traits studied via analysis of evolve and resequence experiments ER - TY - GEN AB - Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response. AU - Castro, João Pl AU - Yancoskie, Michelle N. AU - Marchini, Marta AU - Belohlavy, Stefanie AU - Hiramatsu, Layla AU - Kučka, Marek AU - Beluch, William H. AU - Naumann, Ronald AU - Skuplik, Isabella AU - Cobb, John AU - Barton, Nicholas H AU - Rolian, Campbell AU - Chan, Yingguang Frank ID - 9804 TI - Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice ER - TY - JOUR AB - Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response. AU - Castro, João Pl AU - Yancoskie, Michelle N. AU - Marchini, Marta AU - Belohlavy, Stefanie AU - Hiramatsu, Layla AU - Kučka, Marek AU - Beluch, William H. AU - Naumann, Ronald AU - Skuplik, Isabella AU - Cobb, John AU - Barton, Nicholas H AU - Rolian, Campbell AU - Chan, Yingguang Frank ID - 6713 JF - eLife TI - An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice VL - 8 ER -