An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster

• Published in: PLoS genetics Vol. 12; no. 4; p. e1005987
• Main Authors: Catalán, Ana, Glaser-Schmitt, Amanda, Argyridou, Eliza, Duchen, Pablo, Parsch, John
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.04.2016; Public Library of Science (PLoS)
• Subjects: 3' Untranslated Regions - genetics; Adaptation; Adaptation, Physiological - genetics; Africa South of the Sahara; Animals; Animals, Genetically Modified; Base Sequence - genetics; Biology and life sciences; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Europe; Females; Gene expression; Gene Expression Regulation - genetics; Gene Frequency - genetics; Genetic aspects; Genetic polymorphisms; INDEL Mutation - genetics; Insects; Metallothionein - genetics; Observations; Oxidative stress; Oxidative Stress - genetics; People and Places; Polymorphism; Population; Research and Analysis Methods; Selection, Genetic - genetics; Sequence Analysis, DNA; Sequence Deletion - genetics; Studies; United States; Zinc; Africa South of the Sahara; United States; Europe
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1005987

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.