RT Journal Article
SR Electronic
T1 An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 378711
DO 10.1101/378711
A1 João P. L. Castro
A1 Michelle N. Yancoskie
A1 Marta Marchini
A1 Stefanie Belohlavy
A1 Marek Kučka
A1 William H. Beluch
A1 Ronald Naumann
A1 Isabella Skuplik
A1 John Cobb
A1 Nick H. Barton
A1 Campbell Rolian
A1 Yingguang Frank Chan
YR 2018
UL http://biorxiv.org/content/early/2018/08/19/378711.abstract
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 strong 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 replicate lines. 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 likely to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivation of 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.