The sequence of a male-specific genome region containing the sex determination switch in Aedes aegypti

Joe Turner,Elizabeth R Sutton,Alistair C Darby,Kelly Matzen,Arjen E Van’T Hof,Ritesh Krishna

doi:10.1186/s13071-018-3090-3

Abstract

BackgroundAedes aegypti is the principal vector of several important arboviruses. Among the methods of vector control to limit transmission of disease are genetic strategies that involve the release of sterile or genetically modified non-biting males, which has generated interest in manipulating mosquito sex ratios. Sex determination in Ae. aegypti is controlled by a non-recombining Y chromosome-like region called the M locus, yet characterisation of this locus has been thwarted by the repetitive nature of the genome. In 2015, an M locus gene named Nix was identified that displays the qualities of a sex determination switch.ResultsWith the use of a whole-genome bacterial artificial chromosome (BAC) library, we amplified and sequenced a ~200 kb region containing the male-determining gene Nix. In this study, we show that Nix is comprised of two exons separated by a 99 kb intron primarily composed of repetitive DNA, especially transposable elements.ConclusionsNix, an unusually large and highly repetitive gene, exhibits features in common with Y chromosome genes in other organisms. We speculate that the lack of recombination at the M locus has allowed the expansion of repeats in a manner characteristic of a sex-limited chromosome, in accordance with proposed models of sex chromosome evolution in insects.

Highlights

Aedes aegypti is the principal vector of several important arboviruses
This study identifies and describes the region of the M locus in which Nix is located
Four bacterial artificial chromosome (BAC) clones positive for Nix assembled into a single region of 207 kb with no gaps and a GC content of 40.2%

Summary

Introduction

Among the methods of vector control to limit transmission of disease are genetic strategies that involve the release of sterile or genetically modified non-biting males, which has generated interest in manipulating mosquito sex ratios. Sex determination in Ae. aegypti is controlled by a non-recombining Y chromosome-like region called the M locus, yet characterisation of this locus has been thwarted by the repetitive nature of the genome. The male phenotype is determined by a non-recombining M locus on one copy of autosome 1 [11,12,13] This locus is poorly characterised because its highly repetitive nature has confounded attempts to study it based on the existing genome assembly [14]. The fact that both male and female genomic DNA was used for genome sequencing reduced the expected coverage of the M locus to one quarter of the autosome 1 sequences, further obscuring candidate M locus sequences [18]

Methods

Results

Conclusion