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

Abstract

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.

A clinal polymorphism in the insulin signaling transcription factorfoxocontributes to life-history adaptation inDrosophila

“…Although adaptation genomics can in principle quite readily identify such candidate polymorphisms, a majorbut rarely accomplished-objective is to experimentally validate these candidates as genic targets of selection (Barrett and Hoekstra 2011;Turner 2014;Flatt 2016;Siddiq et al 2017). Thus, with a few exceptions, examples of causative life-history variants remain rare McKechnie et al 2010;Paaby et al 2010;Jones et al 2012;Johnston et al 2013;Méndez-Vigo et al 2013;Paaby et al 2014; Barson et al 2015;Catalán et al 2016;reviewed in Mackay et al 2009;Barrett and Hoekstra 2011).…”

Selective Sweeps

“…There is also agreement that sweeps may be detected with reasonably high confidence if the demographic history of a population is taken into account, except in the case of some complex demographies such as recent severe population size bottlenecks (Pavlidis et al 2010). On the experimental side, however, the search for causative nucleotide changes that led to selective sweeps has started only recently (Saminadin-Peter et al 2012;Voigt et al 2015;Catalán et al 2016), although sweep mapping may lead to quite accurate identification of the targets of selection. Clearly, there is a lot of room for future research activities in this latter area.…”

Three quantitative trait loci explain more than 60% of phenotypic variation for chill coma recovery time inDrosophila ananassae

“…InDel polymorphism is associated with local adaptation to oxidative stress upon migration out of Sub-Saharan Africa into Europe (Catalán et al, 2016). MtnA was downregulated in response to cold in D. melanogaster (von Heckel et al, 2016) but not in D. ananassae (Königer and Grath, 2018).…”

“…melanogaster (MacMillan et al, 2016). Catalán et al, 2016), GF17132 (D.mel/CG5246, von Heckel et al, 2018) QTL3 29 QTL2 spanned 1.0 Mb and contained 138 protein coding genes which were enriched in one molecular function, "serine-type endopeptidase activity" (GO:0004252) and one biological process, "intracellular cholesterol transport" (GO:0032367) (Supplementary file 2: Table S3). Out of the 138 genes, 26 were previously identified as differentially expressed in response to a cold shock.…”