Abstract
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.
Highlights
Understanding how populations adapt to a changing environment is an urgent challenge of global significance
Because beneficial alleles in mammals typically come from standing genetic variation rather than new mutations like in microbes, this loss of diversity would impose a limit on the ability of small populations to adapt
By extending our simulation framework to allow for a major locus against an infinitesimal background, we find that the Nkx3-2 locus would contribute 9.4% of the total selection response in order to produce a shift of 0.7 in allele frequency over 17 generations
Summary
Understanding how populations adapt to a changing environment is an urgent challenge of global significance. Mammals respond readily to selection in many traits, both in nature and in the laboratory (Darwin, 1859; Gingerich, 2001; Garland and Rose, 2009; Keightley et al, 2001) In quantitative genetics, such traits are interpreted as the overall effect from a large set of loci, each with an infinitesimally small (and undetectable) effect (‘infinitesimal model’). The infinitesimal model has performed remarkably well across a wide range of selection experiments, and the model is the basis for commercial breeding (Walsh and Lynch, 2018) It remains unclear what type of genomic change is associated with rapid response to selection, especially in small populations where allele frequency changes can be dominated by random genetic drift
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
