PT  - JOURNAL ARTICLE
AU  - Rowan D.H. Barrett
AU  - Stefan Laurent
AU  - Ricardo Mallarino
AU  - Susanne P. Pfeifer
AU  - Charles C.Y. Xu
AU  - Matthieu Foll
AU  - Kazumasa Wakamatsu
AU  - Jonathan S. Duke-Cohan
AU  - Jeffrey D. Jensen
AU  - Hopi E. Hoekstra
TI  - The fitness consequences of genetic variation in wild populations of mice
AID  - 10.1101/383240
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 383240
4099  - http://biorxiv.org/content/early/2018/08/02/383240.short
4100  - http://biorxiv.org/content/early/2018/08/02/383240.full
AB  - Adaptive evolution can occur when genetic change affects traits subject to natural selection. Although selection is a deterministic process, adaptation can be difficult to predict in finite populations because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these connections using a combination of field and laboratory experiments. We conduct a large-scale manipulative field experiment with wild populations of deer mice in distinct habitats to directly estimate natural selection on pigmentation traits and next test whether this selection drives changes in allele frequency at an underlying pigment locus. We find that divergent cryptic phenotypes are repeatedly favoured in each habitat, leaving footprints of selection in the Agouti gene. Next, using transgenic experiments in Mus, we functionally test one of the Agouti mutations associated with survival, a Serine deletion in exon 2, and find that it causes lighter coat colour via changes in its protein binding properties. Finally, we show significant change in the frequency of this mutation in our field experiment. Together, our findings demonstrate how a sequence variant alters phenotype and show the ensuing ecological consequences that drive changes in population allele frequency, thereby revealing the full process of evolution by natural selection.