An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster.
Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3' untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression variation in natural populations of Drosophila melanogaster. A derived allele of MtnA with a 49-bp deletion in the 3' UTR segregates at high frequency in populations outside of sub-Saharan Africa. The frequency of the deletion increases with latitude across multiple continents and approaches 100% in northern Europe. Flies with the deletion have more than 4-fold higher MtnA expression than flies with the ancestral sequence. Using reporter gene constructs in transgenic flies, we show that the 3' UTR deletion significantly contributes to the observed expression difference. Population genetic analyses uncovered signatures of a selective sweep in the MtnA region within populations from northern Europe. We also find that the 3' UTR deletion is associated with increased oxidative stress tolerance. These results suggest that the 3' UTR deletion has been a target of selection for its ability to confer increased levels of MtnA expression in northern European populations, likely due to a local adaptive advantage of increased oxidative stress tolerance.
Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.|Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, California, United States of America.
Ana
http://orcid.org/0000-0002-4543-748X
A
Catalán
Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.
Amanda
A
Glaser-Schmitt
Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.
Eliza
http://orcid.org/0000-0002-6890-4642
E
Argyridou
Department of Biology and Biochemistry, University of Fribourg, Fribourg, Switzerland.
Pablo
P
Duchen
Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.
John
J
Parsch
D020413:3' Untranslated Regions / Q000235:genetics*; D000222:Adaptation, Physiological / Q000235:genetics*; D017954:Africa South of the Sahara; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005060:Europe; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D054643:INDEL Mutation / Q000235:genetics*; D008668:Metallothionein / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D014481:United States
D020413:3' Untranslated Regions; D008668:Metallothionein