Site-specific genetic engineering of the Anopheles gambiae Y chromosome

Proc Natl Acad Sci U S A. 2014 May 27;111(21):7600-5. doi: 10.1073/pnas.1404996111. Epub 2014 May 12.

Abstract

Despite its function in sex determination and its role in driving genome evolution, the Y chromosome remains poorly understood in most species. Y chromosomes are gene-poor, repeat-rich and largely heterochromatic and therefore represent a difficult target for genetic engineering. The Y chromosome of the human malaria vector Anopheles gambiae appears to be involved in sex determination although very little is known about both its structure and function. Here, we characterize a transgenic strain of this mosquito species, obtained by transposon-mediated integration of a transgene construct onto the Y chromosome. Using meganuclease-induced homologous repair we introduce a site-specific recombination signal onto the Y chromosome and show that the resulting docking line can be used for secondary integration. To demonstrate its utility, we study the activity of a germ-line-specific promoter when located on the Y chromosome. We also show that Y-linked fluorescent transgenes allow automated sex separation of this important vector species, providing the means to generate large single-sex populations. Our findings will aid studies of sex chromosome function and enable the development of male-exclusive genetic traits for vector control.

Keywords: SIT; biotechnology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / genetics*
  • Base Sequence
  • Chromosomes, Artificial, Bacterial
  • Chromosomes, Insect / genetics*
  • DNA Primers / genetics
  • Flow Cytometry
  • Fluorescence
  • Gene Knock-In Techniques
  • Gene Transfer Techniques*
  • Genetic Engineering / methods*
  • In Situ Hybridization, Fluorescence
  • Male
  • Molecular Sequence Data
  • Sequence Analysis, RNA
  • Spermatogenesis / physiology
  • Transgenes / genetics
  • Y Chromosome / genetics*

Substances

  • DNA Primers

Associated data

  • GENBANK/KJ608148
  • GENBANK/KJ608149
  • GENBANK/KJ608150
  • GENBANK/KJ608151
  • GENBANK/KJ608152
  • GENBANK/KJ608153
  • GENBANK/KJ608154
  • GENBANK/KJ608155
  • GENBANK/KJ608156
  • GENBANK/KJ608157
  • GENBANK/KJ608158
  • GENBANK/KJ608159
  • GENBANK/KJ608160