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

摘要

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. Author Summary Although molecular variation is abundant in natural populations, understanding how this variation affects organismal phenotypes that are subject to natural selection remains a major challenge in the field of evolutionary genetics. Here we show that a deletion mutation in a noncoding region of the Drosophila melanogaster Metallothionein A gene leads to a significant increase in gene expression and increases survival under oxidative stress. The deletion is in high frequency in three distinct geographic regions: in northern European populations, in northern populations along the east coast of North America, and in southern populations along the east coast of Australia. In northern European populations the deletion shows population genetic signatures of recent positive selection. Thus, we provide evidence for a regulatory polymorphism that underlies local adaptation in natural populations.