Population Genetic and Functional Analysis of a cis-Regulatory Polymorphism in the Drosophila melanogaster Metallothionein A gene

Genes (Basel). 2019 Feb 14;10(2):147. doi: 10.3390/genes10020147.

Abstract

Although gene expression can vary extensively within and among populations, the genetic basis of this variation and the evolutionary forces that maintain it are largely unknown. In Drosophila melanogaster, a 49-bp insertion/deletion (indel) polymorphism in the Metallothionein A (MtnA) gene is associated with variation in MtnA expression and oxidative stress tolerance. To better understand the functional and evolutionary significance of this polymorphism, we investigated it in several worldwide populations. In a German population, the deletion was present at a high and stable frequency over multiple seasons and years, and was associated with increased MtnA expression. There was, however, no evidence that the polymorphism was maintained by overdominant, seasonally fluctuating, or sexually antagonistic selection. The deletion was rare in a population from the species' ancestral range in sub-Saharan Africa and is likely the result of non-African admixture, suggesting that it spread to high frequency following the species' out-of-Africa expansion. Using data from a North American population, we found that the deletion was associated with MtnA expression and tolerance to oxidative stress induced by menadione sodium bisulfite. Our results are consistent with the deletion being selectively favored in temperate populations due to the increased MtnA expression and oxidative stress tolerance that it confers.

Keywords: Drosophila melanogaster; cis-regulation; deletion; gene expression; indel; oxidative stress; population genetics; untranslated region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics*
  • Africa South of the Sahara
  • Alleles
  • Animals
  • Drosophila melanogaster / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • Genetics, Population
  • INDEL Mutation / genetics
  • Male
  • Metallothionein / genetics*
  • Oxidative Stress / genetics
  • Polymorphism, Genetic
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Sequence Deletion / genetics
  • Stress, Physiological / genetics

Substances

  • Metallothionein