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Tracking allele trajectories over 20 generations of selection for long limbs in mice

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Hiramatsu,  L       
Chan Group, Friedrich Miescher Laboratory, Max Planck Society;

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Kučka,  M       
Chan Group, Friedrich Miescher Laboratory, Max Planck Society;

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Chan,  YF       
Chan Group, Friedrich Miescher Laboratory, Max Planck Society;

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Citation

Hiramatsu, L., Belohlavy, S., Kučka, M., Rolian, C., Barton, N., & Chan, Y. (2019). Tracking allele trajectories over 20 generations of selection for long limbs in mice. In SMBE 2019 (pp. 82).


Cite as: https://hdl.handle.net/21.11116/0000-000D-B565-5
Abstract
Pedigreed selection experiments offer a powerful approach to directly track how genomes evolve under selection. An outstanding example is found in the Longshanks experiment, in which mice in two replicate lines were bred over 20 generations for longer tibiae relative to body mass, resulting in 13-15% increase. We build on our recently published dissection of this selection experiment to investigate the interplay between genetic drift, selection, and the underlying genetic architecture during response to selection. Combining low-pass and linked-read sequencing, we captured allele frequency changes and haplotype segregation across 20 generations. Our time-series reconstruction of allele trajectories allowed estimation of selection and dominance parameters under varying selection or drift models for every locus. Besides discovering additional candidate loci, we also leveraged the time-series information to determine the most likely mode of inheritance governing these loci. We will summarize the relative importance of different allelic interactions in the Longshanks selection response and discuss broader implications for adaptive evolution. Finally, we will present our fine-scale reconstruction of haplotype segregation across the pedigree to investigate how linkage and recombination and selection interact in an empirical, controlled and replicated setting. We show here that despite small population sizes, selection response is rapid and robust in the short term. With nearly complete phenotypic, genomic, and pedigree datasets, the Longshanks experiment provides a comprehensively detailed system to study adaptive genomic evolution.