RT Journal Article
SR Electronic
T1 The genomic and molecular basis of response to selection 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/2018/08/01/378711.abstract
AB A major goal in evolutionary biology is to understand how genomes evolve in response to 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. Using population genetic analysis of sequence data, we identified eight significant loci among a genome-wide polygenic response. Although six of these loci were specific to one of two Longshanks replicates, the two loci with the strongest response were selected in parallel, with the single strongest locus Nkx3-2 accounting for ~9.4% of the overall selection response. Transgenic reporter assays show that both gain- and loss-of-function enhancer variants contributed to the selection response. By integrating multiple lines of evidence, we dissected the selected locus Nkx3-2 down to individual base-pairs and confirm the critical role of cis-regulatory changes in the rapid evolution of a morphological trait.