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Zusammenfassung:
A major goal in evolutionary genetics 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 for longer tibiae relative to body mass over 20 generations, resulting in 13% increase. We combined whole genome sequencing, modeling and population genetics to show that >100 loci contributing to polygenic selection response (See abstract by N. Barton for modelling the Longshanks experiment). Here we will focus on the evolutionary processes underlying loci responding independently and in parallel between the two Longshanks replicate lines. Out of 329 putatively selected outlier loci, more than half of the loci (56%) were specific to one of two Longshanks lines, vs. 27% showing parallel response and 17% other patterns. However, we found that as the selection responses increases, parallelism became increasingly likely. The selected loci showed significant enrichment for limb developmental genes and enhancers, with the impact of cis-acting but not coding changes positively correlating with the strength of selection signature in both Longshanks selection replicate lines. Through functional testing of enhancers at Gli3 and Nkx3-2, we show that both gain- and loss-of-function enhancer variants contributed to selection response. Using the Longshanks experiment we were able to obtain a detailed picture of the polygenic selection response and demonstrate the critical role of regulatory changes for specific loci in rapid intraspecific evolution of a major morphological trait.
