Natural selection in a population of Drosophila melanogaster explained by changes in gene expression caused by sequence variation in core promoter regions.

Mitsuhiko P Sato,Masakado Kawata,Takashi Makino

doi:10.1186/s12862-016-0606-3

Abstract

BackgroundUnderstanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution. Recently, whole-genome sequence analyses have identified regulatory regions subject to natural selection. However, these studies could not identify the relationship between sequence variation in the detected regions and change in gene expression levels. We analyzed sequence variations in core promoter regions, which are critical regions for gene regulation in higher eukaryotes, in a natural population of Drosophila melanogaster, and identified core promoter sequence variations associated with differences in gene expression levels subjected to natural selection.ResultsAmong the core promoter regions whose sequence variation could change transcription factor binding sites and explain differences in expression levels, three core promoter regions were detected as candidates associated with purifying selection or selective sweep and seven as candidates associated with balancing selection, excluding the possibility of linkage between these regions and core promoter regions. CHKov1, which confers resistance to the sigma virus and related insecticides, was identified as core promoter regions that has been subject to selective sweep, although it could not be denied that selection for variation in core promoter regions was due to linked single nucleotide polymorphisms in the regulatory region outside core promoter regions. Nucleotide changes in core promoter regions of CHKov1 caused the loss of two basal transcription factor binding sites and acquisition of one transcription factor binding site, resulting in decreased gene expression levels. Of nine core promoter regions regions associated with balancing selection, brat, and CG9044 are associated with neuromuscular junction development, and Nmda1 are associated with learning, behavioral plasticity, and memory. Diversity of neural and behavioral traits may have been maintained by balancing selection.ConclusionsOur results revealed the evolutionary process occurring by natural selection for differences in gene expression levels caused by sequence variation in core promoter regions in a natural population. The sequences of core promoter regions were diverse even within the population, possibly providing a source for natural selection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0606-3) contains supplementary material, which is available to authorized users.

Highlights

Understanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution
Detecting transcripts whose expression variation was explained by sequence variation Genome and transcriptome data from a natural North American population of D. melanogaster was used to estimate the relative contribution of core promoter region (CPR) to changes in gene expression levels by sequence mutations in CPRs
Linear model analysis showed that among the 6617 expressed transcripts with high heritability and polymorphic sites and without undetermined nucleotides, 996 (14.65 %) expression variations were significantly associated with sequence differences in CPRs after Benjamini-Hochberg multiple-test correction (Fig. 1 and Additional file 1)

Summary

Introduction

Understanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution. Even for sequences of gene regulatory regions, several methods have been proposed and genome-wide analyses have shown statistical evidence of natural selection in non-coding and cis-regulatory regions [5,6,7] These studies focused on nucleotide substitutions in regulatory sequences or transcription factor binding sites (TFBSs) between species and did not evaluate recent or ongoing selection for standing genetic variation in natural populations. It is unknown how sequence differences affect the binding of transcription factors and regulate gene expression. This study did not show how variations in regulatory sequences affected gene expression levels

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