title: Dissecting the Genetic Basis of a Complex cis-Regulatory Adaptation.
abstract: Although single genes underlying several evolutionary adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. Here we report that the budding yeast Saccharomyces paradoxus has recently evolved resistance to citrinin, a naturally occurring mycotoxin. Applying a genome-wide test for selection on cis-regulation, we identified five genes involved in the citrinin response that are constitutively up-regulated in S. paradoxus. Four of these genes are necessary for resistance, and are also sufficient to increase the resistance of a sensitive strain when over-expressed. Moreover, cis-regulatory divergence in the promoters of these genes contributes to resistance, while exacting a cost in the absence of citrinin. Our results demonstrate how the subtle effects of individual regulatory elements can be combined, via natural selection, into a complex adaptation. Our approach can be applied to dissect the genetic basis of polygenic adaptations in a wide range of species.
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Santiago
authors.initials: S
authors.lastname: Naranjo
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, United States of America.|Stanford Genome Technology Center, Stanford University, Stanford, California, United States of America.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Carlo G
authors.initials: CG
authors.lastname: Artieri
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Mian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Palmer
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Fraser
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000935:Antifungal Agents / Q000633:toxicity; D002953:Citrinin / Q000633:toxicity; D025141:Drug Resistance, Fungal / Q000235:genetics; D005800:Genes, Fungal; D056084:Genetic Fitness; D011401:Promoter Regions, Genetic; D012440:Saccharomyces / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: D000935:Antifungal Agents; D002953:Citrinin